title
Manolis Kellis: Biology of Disease | Lex Fridman Podcast #133

description
Manolis Kellis is a computational biologist at MIT. Please support this podcast by checking out our sponsors: - SEMrush: https://www.semrush.com/partner/lex/ to get a free month of Guru - Pessimists Archive: https://pessimists.co/ - Eight Sleep: https://www.eightsleep.com/lex and use code LEX to get $200 off - BetterHelp: https://betterhelp.com/lex to get 10% off EPISODE LINKS: Manolis Website: http://web.mit.edu/manoli/ Manolis Twitter: https://twitter.com/manoliskellis Manolis YouTube: https://www.youtube.com/channel/UCkKlJ5LHrE3C7fgbnPA5DGA Manolis Wikipedia: https://en.wikipedia.org/wiki/Manolis_Kellis PODCAST INFO: Podcast website: https://lexfridman.com/podcast Apple Podcasts: https://apple.co/2lwqZIr Spotify: https://spoti.fi/2nEwCF8 RSS: https://lexfridman.com/feed/podcast/ Full episodes playlist: https://www.youtube.com/playlist?list=PLrAXtmErZgOdP_8GztsuKi9nrraNbKKp4 Clips playlist: https://www.youtube.com/playlist?list=PLrAXtmErZgOeciFP3CBCIEElOJeitOr41 OUTLINE: 0:00 - Introduction 2:49 - Molecular basis for human disease 26:48 - Deadliest diseases 32:31 - Genetic component of diseases 41:22 - Genetic understanding of disease 57:09 - Unified theory of human disease 1:03:10 - Genome circuitry 1:28:13 - CRISPR 1:39:50 - Mitochondria 1:47:54 - Future of biology research 2:17:30 - The genetic circuitry of disease CONNECT: - Subscribe to this YouTube channel - Twitter: https://twitter.com/lexfridman - LinkedIn: https://www.linkedin.com/in/lexfridman - Facebook: https://www.facebook.com/LexFridmanPage - Instagram: https://www.instagram.com/lexfridman - Medium: https://medium.com/@lexfridman - Support on Patreon: https://www.patreon.com/lexfridman

detail
{'title': 'Manolis Kellis: Biology of Disease | Lex Fridman Podcast #133', 'heatmap': [{'end': 466.582, 'start': 369.919, 'weight': 1}, {'end': 7346.464, 'start': 7249.27, 'weight': 0.83}], 'summary': 'Manolis kellis, a professor at mit, discusses the latest state-of-the-art research in science, biology, and genetics, exploring the complexity and robustness of biology, the impact of genetic variation on disease, the influence of genetic and environmental factors on diseases, crispr technology, and technological and computational advances in biology, emphasizing the potential for disease understanding and therapeutics.', 'chapters': [{'end': 114.957, 'segs': [{'end': 71.287, 'src': 'embed', 'start': 0.109, 'weight': 0, 'content': [{'end': 5.033, 'text': 'The following is a conversation with Manolis Kellis, his third time on the podcast.', 'start': 0.109, 'duration': 4.924}, {'end': 10.597, 'text': "He's a professor at MIT and head of the MIT Computational Biology Group.", 'start': 5.573, 'duration': 5.024}, {'end': 16.461, 'text': 'This time we went deep on the science, biology and genetics.', 'start': 11.258, 'duration': 5.203}, {'end': 19.103, 'text': 'So this is a bit of an experiment.', 'start': 17.102, 'duration': 2.001}, {'end': 25.829, 'text': 'Manolis went back and forth between the basics of biology to the latest state-of-the-art in the research.', 'start': 19.884, 'duration': 5.945}, {'end': 30.452, 'text': "He's a master at this, so I just sat back and enjoyed the ride.", 'start': 26.549, 'duration': 3.903}, {'end': 37.818, 'text': "This conversation happened at 7 a.m., so it's yet another podcast episode after an all-nighter for me.", 'start': 31.133, 'duration': 6.685}, {'end': 45.464, 'text': 'And once again, since the universe has a sense of humor, this one was a tough one for my brain to keep up,', 'start': 38.318, 'duration': 7.146}, {'end': 49.487, 'text': 'but I did my best and I never shy away from a good challenge.', 'start': 45.464, 'duration': 4.023}, {'end': 54.351, 'text': 'Quick mention of each sponsor, followed by some thoughts related to the episode.', 'start': 50.328, 'duration': 4.023}, {'end': 61.418, 'text': "First is SEMrush, the most advanced SEO optimization tool I've ever come across.", 'start': 55.673, 'duration': 5.745}, {'end': 65.542, 'text': "I don't like looking at numbers, but someone probably should.", 'start': 62.299, 'duration': 3.243}, {'end': 67.544, 'text': 'It helps you make good decisions.', 'start': 65.562, 'duration': 1.982}, {'end': 70.407, 'text': 'Second is Pessimist Archive.', 'start': 68.485, 'duration': 1.922}, {'end': 71.287, 'text': "They're back.", 'start': 70.747, 'duration': 0.54}], 'summary': 'Manolis kellis discusses science, biology, and genetics in a deep dive interview at 7 a.m., mit computational biology group head.', 'duration': 71.178, 'max_score': 0.109, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI109.jpg'}], 'start': 0.109, 'title': 'Manolis kellis on science, biology, and genetics', 'summary': 'Delves into science, biology, and genetics with manolis kellis, a professor at mit, covering the latest state-of-the-art research.', 'chapters': [{'end': 114.957, 'start': 0.109, 'title': 'Manolis kellis on science, biology, and genetics', 'summary': "Delves deep into science, biology, and genetics with manolis kellis, a professor at mit, covering the latest state-of-the-art research, despite the conversation happening at 7 a.m. and the host's fatigue after an all-nighter.", 'duration': 114.848, 'highlights': ['Manolis Kellis, a professor at MIT and head of the MIT Computational Biology Group, discusses the latest state-of-the-art research in science, biology, and genetics, providing insights into advanced topics.', "The conversation took place at 7 a.m., showcasing the dedication of the participants, despite the host's fatigue after an all-nighter, highlighting the commitment to delivering valuable content to the audience.", "The host mentions SEMrush, Pessimist Archive, Eight Sleep, and Better Help as sponsors, emphasizing the diverse range of products and services related to SEO optimization, history podcasts, sleep technology, and online therapy, providing a comprehensive overview of the episode's sponsors."]}], 'duration': 114.848, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI109.jpg', 'highlights': ['Manolis Kellis, a professor at MIT, discusses the latest state-of-the-art research in science, biology, and genetics.', 'The conversation took place at 7 a.m., showcasing the dedication of the participants.', 'The host mentions SEMrush, Pessimist Archive, Eight Sleep, and Better Help as sponsors, emphasizing the diverse range of products and services related to SEO optimization, history podcasts, sleep technology, and online therapy.']}, {'end': 1605.023, 'segs': [{'end': 137.372, 'src': 'embed', 'start': 114.957, 'weight': 0, 'content': [{'end': 124.943, 'text': 'let me say that biology in the brain and in the various systems of the body fill me with awe every time I think about how such a chaotic mess,', 'start': 114.957, 'duration': 9.986}, {'end': 127.445, 'text': 'coming from its humble origins in the ocean,', 'start': 124.943, 'duration': 2.502}, {'end': 137.372, 'text': 'was able to achieve such incredibly complex and robust mechanisms of life that survived despite all the forces of nature that want to destroy it.', 'start': 127.445, 'duration': 9.927}], 'summary': "Biology's evolution from ocean origins to complex, robust survival mechanisms is awe-inspiring.", 'duration': 22.415, 'max_score': 114.957, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI114957.jpg'}, {'end': 310.728, 'src': 'embed', 'start': 281.689, 'weight': 1, 'content': [{'end': 287.093, 'text': 'You would start with the animal models, the eukaryotic models, the mammalian models, and then you would go to human.', 'start': 281.689, 'duration': 5.404}, {'end': 297.42, 'text': 'Human genetics has been so transformed in the last decade or two that human genetics is now actually driving the basic biology.', 'start': 288.454, 'duration': 8.966}, {'end': 305.386, 'text': 'There is more genetic mutation information in the human genome than there will ever be in any other species.', 'start': 298.301, 'duration': 7.085}, {'end': 310.728, 'text': 'What do you mean by mutation information? So perturbations is how you understand systems.', 'start': 306.147, 'duration': 4.581}], 'summary': 'Human genetics drives basic biology; more genetic mutations in human genome than in any other species.', 'duration': 29.039, 'max_score': 281.689, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI281689.jpg'}, {'end': 466.582, 'src': 'heatmap', 'start': 369.919, 'weight': 1, 'content': [{'end': 379.238, 'text': 'so the way that i like to describe it is that traditionally, epidemiology, which is basically the study of disease, you know,', 'start': 369.919, 'duration': 9.319}, {'end': 385.224, 'text': 'sort of the observational study of disease has been about correlating one thing with another thing.', 'start': 379.238, 'duration': 5.986}, {'end': 393.752, 'text': 'So if you have a lot of people with liver disease who are also alcoholics, you might say well, maybe the alcoholism is driving the liver disease,', 'start': 385.744, 'duration': 8.008}, {'end': 396.315, 'text': 'or maybe those who have liver disease self-medicate with alcohol.', 'start': 393.752, 'duration': 2.563}, {'end': 398.657, 'text': 'So the connection could be either way.', 'start': 396.755, 'duration': 1.902}, {'end': 409.385, 'text': "With genetic epidemiology, it's about correlating changes in the genome with phenotypic differences, and then you know the direction of causality.", 'start': 399.978, 'duration': 9.407}, {'end': 417.831, 'text': 'So if you know that a particular gene is related to the disease, you can basically say okay,', 'start': 410.065, 'duration': 7.766}, {'end': 422.474, 'text': 'perturbing that gene in mouse causes the mice to have X phenotype.', 'start': 417.831, 'duration': 4.643}, {'end': 427.649, 'text': 'So perturbing that gene in human causes the humans to have the disease.', 'start': 423.843, 'duration': 3.806}, {'end': 438.411, 'text': 'So I can now figure out what are the detailed molecular phenotypes in the human that are related to that organismal phenotype in the disease.', 'start': 428.21, 'duration': 10.201}, {'end': 444.452, 'text': "So it's all about understanding disease mechanism, understanding what are the pathways, what are the tissues,", 'start': 438.791, 'duration': 5.661}, {'end': 448.533, 'text': 'what are the processes that are associated with the disease, so that we know how to intervene.', 'start': 444.452, 'duration': 4.081}, {'end': 452.854, 'text': 'You can then prescribe particular medications that also alter these processes.', 'start': 448.953, 'duration': 3.901}, {'end': 457.775, 'text': 'You can prescribe lifestyle changes that also affect these processes and so on and so forth.', 'start': 453.314, 'duration': 4.461}, {'end': 461.24, 'text': "That's such a beautiful puzzle to try to solve, like,", 'start': 458.018, 'duration': 3.222}, {'end': 466.582, 'text': 'what kind of perturbations eventually have this ripple effect that leads to disease across the population?', 'start': 461.24, 'duration': 5.342}], 'summary': 'Genetic epidemiology focuses on correlating genome changes with phenotypic differences to understand disease mechanisms and intervention strategies.', 'duration': 96.663, 'max_score': 369.919, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI369919.jpg'}, {'end': 753.071, 'src': 'embed', 'start': 728.373, 'weight': 2, 'content': [{'end': 735.7, 'text': 'So we basically have something like seven billion people on the planet, and every one of them carries something like six million mutations.', 'start': 728.373, 'duration': 7.327}, {'end': 746.807, 'text': 'you basically have an enormous matrix of genotype by phenotype by systematically measuring the phenotype of these individuals.', 'start': 736.701, 'duration': 10.106}, {'end': 753.071, 'text': 'And the traditional way of measuring this phenotype has been to look at one trait at a time.', 'start': 747.868, 'duration': 5.203}], 'summary': '7 billion people carry around 6 million mutations, leading to a vast matrix of genotype by phenotype.', 'duration': 24.698, 'max_score': 728.373, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI728373.jpg'}, {'end': 1201.453, 'src': 'embed', 'start': 1178.357, 'weight': 3, 'content': [{'end': 1187.699, 'text': "And then looked at that map where you're asking what are the individual genetic perturbations and how are they related to all the way to Alzheimer's disease?", 'start': 1178.357, 'duration': 9.342}, {'end': 1190.704, 'text': 'And that has actually been quite successful.', 'start': 1188.419, 'duration': 2.285}, {'end': 1198.479, 'text': "So we now have more than 27 different loci, these are genomic regions, that are associated with Alzheimer's.", 'start': 1191.225, 'duration': 7.254}, {'end': 1201.453, 'text': 'at this end-to-end level.', 'start': 1199.551, 'duration': 1.902}], 'summary': "Over 27 genomic regions linked to alzheimer's disease identified successfully.", 'duration': 23.096, 'max_score': 1178.357, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI1178357.jpg'}], 'start': 114.957, 'title': 'Complex biological mechanisms', 'summary': 'Explores the complexity and robustness of biology, the shift in understanding human disease, the impact of genetic variation on disease, and the intricate nature of the human brain, presenting a challenging but promising puzzle for researchers in the field.', 'chapters': [{'end': 159.657, 'start': 114.957, 'title': "Biology's complex mechanisms", 'summary': 'Discusses the awe-inspiring complexity and robustness of biology, contrasting it with human-engineered computing systems, and the potential need to rethink engineering computational systems for achieving artificial general intelligence and consciousness.', 'duration': 44.7, 'highlights': ['The awe-inspiring complexity and robustness of biology is contrasted with human-engineered computing systems, prompting a potential need to rethink engineering computational systems for artificial general intelligence and consciousness.', "The chaotic mess of biology's humble origins in the ocean has achieved incredibly complex and robust mechanisms of life that have survived despite all the forces of nature. This demonstrates the resilience and adaptability of biological systems.", 'The discussion emphasizes the need to rethink how computational systems are engineered in order to create artificial general intelligence and artificial consciousness, suggesting a significant shift in approach may be necessary.', 'The speaker expresses awe at the ability of biology to achieve complex and robust mechanisms of life despite coming from humble origins in the ocean, highlighting the remarkable resilience and adaptability of biological systems.', 'The transcript concludes with a call to action for audience engagement, encouraging subscriptions on YouTube, five-star reviews on Apple Podcasts, and following on Spotify as a means of support and appreciation.']}, {'end': 652.07, 'start': 159.657, 'title': 'Understanding human disease complexity', 'summary': 'Discusses the complexities of understanding human disease, emphasizing the shift in basic biology from model organisms to human genetics, and the use of perturbations to understand disease mechanisms and interventions.', 'duration': 492.413, 'highlights': ['Human genetics is now driving basic biology, with more genetic mutation information in the human genome than in any other species, transforming the traditional approach of understanding disease complexity through model organisms.', 'Perturbations are used to understand disease mechanisms, with genetic epidemiology correlating changes in the genome with phenotypic differences to determine causality and identify detailed molecular phenotypes related to the disease.', 'Every individual carries six million unique genetic variants, serving as tiny perturbations that contribute to phenotypic differences, influencing the complexity of understanding human disease.', 'Power analysis is conducted to determine the effect size and natural variation in perturbations, impacting the ability to detect and understand the implications of genetic variations on disease.']}, {'end': 1019.154, 'start': 652.651, 'title': 'Genetic variation and disease research', 'summary': 'Discusses the impact of genetic variation on disease, emphasizing the potential for genetic perturbations to lead to illness and the current approach of leveraging large-scale genetic and phenotypic data to deconvolve the complexities of disease at multiple biological levels, presenting a promising yet challenging puzzle for researchers in the field.', 'duration': 366.503, 'highlights': ['Large-scale genetic and phenotypic data Leveraging data from seven billion individuals, each carrying approximately six million mutations, to systematically measure phenotypes across hundreds of traits, providing a comprehensive view of genetic variation and its impact on disease.', 'Transition from family pedigrees to unrelated individuals Shifting from the traditional approach of studying familial genetic patterns to analyzing thousands of unrelated individuals with various genetic variants and phenotypes, offering a modern perspective on genetic research and disease association.', 'Deconvolution of genetic variation at multiple biological levels Utilizing computational methods to unravel the intricate relationship between genetic variation and molecular changes at the expression and regulatory levels, enabling the systematic analysis of genetic perturbations across different biological contexts and disease states.', 'Experimental dissection of disease complexity Balancing computational complexity with experimental approaches to dissect the layers of disease complexity, allowing researchers to unravel the effects of genetic perturbations at various biological levels and develop targeted strategies for disease intervention.']}, {'end': 1605.023, 'start': 1019.154, 'title': 'Understanding the complexity of the human brain', 'summary': "Discusses the intricate nature of the human brain, emphasizing the complexity of its cellular composition, genetic variations related to alzheimer's disease, and the potential for measuring and understanding cognitive and behavioral phenotypes.", 'duration': 585.869, 'highlights': ["Human genetics has identified over 27 different genomic regions associated with Alzheimer's disease, showcasing the success of linking genetic perturbations to disease. Human genetics has successfully linked over 27 genomic regions to Alzheimer's disease, demonstrating the ability to connect genetic variations to the development of the illness.", 'The exploration of epigenomic alterations at the gene regulatory level demonstrates substantial effects, offering potential insights into disease mechanisms. The study of epigenomic alterations at the gene regulatory level reveals significant effects, providing potential insights into the mechanisms underlying diseases.', 'The ability to measure various properties of cells, including calcium influx rate, synaptic density, and electric impulse conductivity, provides avenues for understanding the path to disease. The capacity to measure cell properties such as calcium influx rate, synaptic density, and electric impulse conductivity offers opportunities to comprehend the progression of diseases.', 'Advancements in measuring cognitive and behavioral phenotypes, including intelligence, memory, and empathy, offer a more comprehensive understanding of human functioning and its genetic underpinnings. Progress in measuring cognitive and behavioral phenotypes, such as intelligence, memory, and empathy, contributes to a more comprehensive understanding of human functioning and its genetic basis.']}], 'duration': 1490.066, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI114957.jpg', 'highlights': ['The awe-inspiring complexity and robustness of biology contrasts with human-engineered computing systems, prompting a potential need to rethink engineering computational systems for artificial general intelligence and consciousness.', 'Human genetics is now driving basic biology, with more genetic mutation information in the human genome than in any other species, transforming the traditional approach of understanding disease complexity through model organisms.', 'Large-scale genetic and phenotypic data leveraging data from seven billion individuals, each carrying approximately six million mutations, to systematically measure phenotypes across hundreds of traits, providing a comprehensive view of genetic variation and its impact on disease.', "Human genetics has identified over 27 different genomic regions associated with Alzheimer's disease, showcasing the success of linking genetic perturbations to disease."]}, {'end': 2538.641, 'segs': [{'end': 1662.977, 'src': 'embed', 'start': 1630.43, 'weight': 1, 'content': [{'end': 1632.632, 'text': 'One is lifestyle impact.', 'start': 1630.43, 'duration': 2.202}, {'end': 1636.155, 'text': 'I mean, if you look at COVID, the impact on lifestyle has been enormous.', 'start': 1632.652, 'duration': 3.503}, {'end': 1645.664, 'text': 'So, understanding COVID is important because it has impacted the wellbeing in terms of ability to have a job, ability to have an apartment,', 'start': 1636.376, 'duration': 9.288}, {'end': 1649.768, 'text': 'ability to go to work, ability to have a mental circle of support.', 'start': 1645.664, 'duration': 4.104}, {'end': 1654.992, 'text': 'And all of that for, you know, millions of Americans, like huge, huge impact.', 'start': 1650.709, 'duration': 4.283}, {'end': 1656.933, 'text': "So that's one aspect of importance.", 'start': 1655.452, 'duration': 1.481}, {'end': 1662.977, 'text': "So basically mental disorders, Alzheimer's has a huge importance in the well-being of Americans.", 'start': 1656.953, 'duration': 6.024}], 'summary': "Covid has had enormous impact on americans' lifestyle and wellbeing, affecting job security, housing, work, and support networks, with significant implications for mental health and wellbeing.", 'duration': 32.547, 'max_score': 1630.43, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI1630430.jpg'}, {'end': 1704.999, 'src': 'embed', 'start': 1674.765, 'weight': 0, 'content': [{'end': 1678.928, 'text': 'Absolutely The second metric, which is much easier to quantify, is deaths.', 'start': 1674.765, 'duration': 4.163}, {'end': 1684.32, 'text': 'What is the number one killer? The number one killer is actually heart disease.', 'start': 1680.031, 'duration': 4.289}, {'end': 1686.765, 'text': 'It is actually killing 650,000 Americans per year.', 'start': 1684.741, 'duration': 2.024}, {'end': 1693.271, 'text': 'Number two is cancer with 600,000 Americans.', 'start': 1690.549, 'duration': 2.722}, {'end': 1696.913, 'text': 'Number three, far, far down the list is accidents.', 'start': 1694.111, 'duration': 2.802}, {'end': 1699.075, 'text': 'Every single accident combined.', 'start': 1697.574, 'duration': 1.501}, {'end': 1704.999, 'text': 'So basically you, you know, you read the news, accidents, like, you know, there was a huge car crash all over the news.', 'start': 1699.515, 'duration': 5.484}], 'summary': 'Heart disease kills 650,000 americans per year, followed by cancer at 600,000.', 'duration': 30.234, 'max_score': 1674.765, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI1674765.jpg'}, {'end': 1869.629, 'src': 'embed', 'start': 1833.01, 'weight': 3, 'content': [{'end': 1836.491, 'text': "it's extremely detrimental for you, like a lot of processed food, et cetera.", 'start': 1833.01, 'duration': 3.481}, {'end': 1843.094, 'text': 'So if we change that equation and as a society we made availability of healthy food much,', 'start': 1836.912, 'duration': 6.182}, {'end': 1852.458, 'text': "much easier and charged a burger at McDonald's the price that it costs on the health system,", 'start': 1843.094, 'duration': 9.364}, {'end': 1856.201, 'text': 'then people would actually start buying more healthy foods.', 'start': 1852.458, 'duration': 3.743}, {'end': 1859.102, 'text': "So basically that's sort of a societal intervention, if you wish.", 'start': 1856.281, 'duration': 2.821}, {'end': 1869.629, 'text': 'In the same way, increasing empathy, increasing education, increasing the social framework and support would basically lead to fewer suicides.', 'start': 1859.543, 'duration': 10.086}], 'summary': 'Making healthy food more accessible and increasing societal support can reduce health issues and suicide rates.', 'duration': 36.619, 'max_score': 1833.01, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI1833010.jpg'}, {'end': 1962.95, 'src': 'embed', 'start': 1938.321, 'weight': 4, 'content': [{'end': 1944.284, 'text': 'read more books, learn a foreign language, go running, sort of have a more fulfilling life.', 'start': 1938.321, 'duration': 5.963}, {'end': 1951.187, 'text': "All of that will actually decrease Alzheimer's, but there's a limit to how much that can impact because of the huge genetic footprint.", 'start': 1944.744, 'duration': 6.443}, {'end': 1952.028, 'text': 'So this is fascinating.', 'start': 1951.207, 'duration': 0.821}, {'end': 1958.39, 'text': 'So each one of these problems have, a genetic component and an environment component.', 'start': 1952.048, 'duration': 6.342}, {'end': 1961.35, 'text': "And so like when there's a genetic component?", 'start': 1958.79, 'duration': 2.56}, {'end': 1962.95, 'text': 'what can we do about some of these diseases?', 'start': 1961.35, 'duration': 1.6}], 'summary': "Engaging in activities like reading, learning a language, and exercising can decrease alzheimer's risk, but genetics also play a significant role in disease development.", 'duration': 24.629, 'max_score': 1938.321, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI1938321.jpg'}, {'end': 2092.286, 'src': 'embed', 'start': 2055.956, 'weight': 6, 'content': [{'end': 2059.639, 'text': 'you can just poke another hole at the bathtub and just get a lot of the fat out.', 'start': 2055.956, 'duration': 3.683}, {'end': 2060.882, 'text': "Yeah That's fascinating.", 'start': 2059.659, 'duration': 1.223}, {'end': 2065.047, 'text': "Yeah So we're not just passive observers of our genetics.", 'start': 2061.703, 'duration': 3.344}, {'end': 2068.913, 'text': 'The more we understand, the more we can come up with actual treatments.', 'start': 2065.809, 'duration': 3.104}, {'end': 2077.498, 'text': "And I think that's an important aspect to realize when people are thinking about strong effect versus weak effect variants.", 'start': 2069.554, 'duration': 7.944}, {'end': 2079.46, 'text': 'So some variants have strong effects.', 'start': 2078.018, 'duration': 1.442}, {'end': 2081.301, 'text': 'We talked about these Mendelian disorders,', 'start': 2079.52, 'duration': 1.781}, {'end': 2092.286, 'text': 'where a single gene has a sufficiently large effect pen and trans expressivity and so forth that basically you can trace it in families with cases and not cases,', 'start': 2081.301, 'duration': 10.985}], 'summary': 'Understanding genetics can lead to treatments; some variants have strong effects.', 'duration': 36.33, 'max_score': 2055.956, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI2055956.jpg'}, {'end': 2197.588, 'src': 'embed', 'start': 2170.766, 'weight': 5, 'content': [{'end': 2176.761, 'text': 'And those genes that have very little variation but no association with disease.', 'start': 2170.766, 'duration': 5.995}, {'end': 2181.723, 'text': "that's a very good metric to say oh, that's probably a developmental gene because we're not good at measuring those phenotypes.", 'start': 2176.761, 'duration': 4.962}, {'end': 2188.205, 'text': "So it's genes that you can tell evolution has excluded mutations from,", 'start': 2182.803, 'duration': 5.402}, {'end': 2191.426, 'text': "but yet we can't see them associated with anything that we can measure nowadays.", 'start': 2188.205, 'duration': 3.221}, {'end': 2193.606, 'text': "It's probably early embryonic lethal.", 'start': 2192.086, 'duration': 1.52}, {'end': 2197.588, 'text': 'What are all the words you just said? Early embryonic what? Lethal.', 'start': 2194.727, 'duration': 2.861}], 'summary': 'Genes with little variation and no disease association likely indicate early embryonic lethality.', 'duration': 26.822, 'max_score': 2170.766, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI2170766.jpg'}, {'end': 2292.002, 'src': 'embed', 'start': 2267.211, 'weight': 7, 'content': [{'end': 2276.422, 'text': 'Yeah, So mammals have basically evolved mechanisms for fail fast where basically in those early months of development.', 'start': 2267.211, 'duration': 9.211}, {'end': 2277.884, 'text': "I mean it's horrendous.", 'start': 2276.422, 'duration': 1.462}, {'end': 2283.431, 'text': 'of course, at the personal level, when you lose a, you know your future child,', 'start': 2277.884, 'duration': 5.547}, {'end': 2292.002, 'text': "but in some ways there's so little hope for that child to develop and sort of make it through the remaining months.", 'start': 2283.431, 'duration': 8.571}], 'summary': "Mammals have evolved fail-fast mechanisms in early development, leading to little hope for the child's survival.", 'duration': 24.791, 'max_score': 2267.211, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI2267211.jpg'}, {'end': 2369.157, 'src': 'embed', 'start': 2338.702, 'weight': 8, 'content': [{'end': 2340.725, 'text': 'The ones that only have weak effect mutations.', 'start': 2338.702, 'duration': 2.023}, {'end': 2350.147, 'text': 'By understanding through genetics that they have a weak effect mutation and understanding that they have a causal role on the disease,', 'start': 2341.963, 'duration': 8.184}, {'end': 2351.248, 'text': 'we can then say okay great.', 'start': 2350.147, 'duration': 1.101}, {'end': 2354.509, 'text': 'Evolution has only tolerated a 2% change in that gene.', 'start': 2351.308, 'duration': 3.201}, {'end': 2359.952, 'text': 'Pharmaceutically, I can go in and induce a 70% change in that gene.', 'start': 2355.65, 'duration': 4.302}, {'end': 2369.157, 'text': 'And maybe I will poke another hole at the bathtub that was not easy to control.', 'start': 2361.233, 'duration': 7.924}], 'summary': 'Genetic understanding enables 70% gene change, surpassing 2% tolerated evolution.', 'duration': 30.455, 'max_score': 2338.702, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI2338702.jpg'}, {'end': 2516.243, 'src': 'embed', 'start': 2485.292, 'weight': 9, 'content': [{'end': 2495.478, 'text': "Then what have we been able to find in terms of which disease could be helped? Again, don't get me started.", 'start': 2485.292, 'duration': 10.186}, {'end': 2498.419, 'text': 'We have found so much.', 'start': 2497.218, 'duration': 1.201}, {'end': 2505.16, 'text': 'Our understanding of disease has changed so dramatically with genetics.', 'start': 2498.919, 'duration': 6.241}, {'end': 2508.361, 'text': 'I mean, places that we had no idea would be involved.', 'start': 2506, 'duration': 2.361}, {'end': 2516.243, 'text': 'So one of the worst things about my genome is that I have a genetic predisposition to age-related macular degeneration, AMD.', 'start': 2508.921, 'duration': 7.322}], 'summary': 'Genetics has dramatically changed disease understanding, identifying a genetic predisposition to age-related macular degeneration.', 'duration': 30.951, 'max_score': 2485.292, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI2485292.jpg'}], 'start': 1605.023, 'title': 'Genetics and disease impact', 'summary': 'Discusses the importance of understanding diseases based on their impact on lifestyle, well-being, and mortality, including the influence of genetic and environmental factors, and the fail fast principle in mammalian development, with a focus on age-related macular degeneration.', 'chapters': [{'end': 1859.102, 'start': 1605.023, 'title': 'Understanding disease impact', 'summary': 'Discusses the importance of understanding diseases based on their impact on lifestyle, well-being, and mortality, emphasizing the significance of diseases such as heart disease, cancer, and covid-19.', 'duration': 254.079, 'highlights': ['Heart disease is the number one killer, causing 650,000 deaths per year in the US. Heart disease ranks as the top cause of death in the US, resulting in 650,000 deaths annually, highlighting its significant impact on mortality.', "COVID-19 has had a substantial impact on well-being, affecting millions of Americans' ability to work and have a support network. The discussion emphasizes the immense impact of COVID-19 on the well-being of individuals, affecting their job security, housing, and social support, underscoring the disease's significance in terms of lifestyle impact.", 'Cancer is the second leading cause of death, resulting in 600,000 deaths annually in the US. With 600,000 deaths per year, cancer is highlighted as the second leading cause of mortality, emphasizing its considerable impact on the population.', 'The availability of healthy food and societal interventions can potentially address the impact of diseases like obesity and diabetes. The discussion underscores the potential impact of societal interventions such as improving the availability of healthy food to address diseases like obesity and diabetes, emphasizing the potential for societal changes to mitigate the impact of certain diseases.']}, {'end': 2191.426, 'start': 1859.543, 'title': 'Genetics and disease intervention', 'summary': "Discusses the impact of increasing empathy, education, and social support in reducing suicides, murders, and overall deaths, as well as the influence of genetic and environmental factors on diseases such as alzheimer's and heart disease, emphasizing the potential of understanding genetic mechanisms to intervene in disease development and the significance of genes with minimal variation in disease association.", 'duration': 331.883, 'highlights': ["Understanding the genetic component can have a huge impact on the environmental component, as genetics provides access to mechanisms that can potentially counteract some environmental components, such as in the case of Alzheimer's. Understanding genetics can influence the mechanism to counteract environmental components, potentially decreasing the impact of diseases like Alzheimer's.", 'Genes with minimal variation but no association with disease can be considered developmental genes, providing insights into the importance of genes based on their variation and disease association. Genes with minimal variation but no association with disease can be indicative of developmental genes.', "Emphasizing the impact of genetics in understanding disease mechanisms and intervention, particularly in manipulating metabolic processes to counteract environmental influences, exemplified by the analogy of obesity as a 'bathtub of fat.' Genetics can be utilized to manipulate metabolic processes to counteract environmental influences, as demonstrated by the analogy of obesity as a 'bathtub of fat.'"]}, {'end': 2538.641, 'start': 2192.086, 'title': 'Genetics and disease: fail fast principle', 'summary': 'Discusses the fail fast principle in mammalian development, the impact of genetic mutations on disease, and the potential for pharmaceutical intervention, with a focus on age-related macular degeneration.', 'duration': 346.555, 'highlights': ['Mammals have evolved mechanisms for fail fast in early embryonic development, with an enormous investment in resources for newborns, contributing to a good evolutionary principle. Mammals have evolved mechanisms for fail fast in early embryonic development, with an enormous investment in resources for newborns, contributing to a good evolutionary principle.', 'Understanding genetic mutations and their impact on disease can guide pharmaceutical intervention, with the potential for inducing significant changes in genes correlated with disease, offering new possibilities for treatment. Understanding genetic mutations and their impact on disease can guide pharmaceutical intervention, with the potential for inducing significant changes in genes correlated with disease, offering new possibilities for treatment.', 'Genetics has significantly changed the understanding of disease, identifying unexpected genetic predispositions to conditions such as age-related macular degeneration (AMD), which opens up new opportunities for targeted interventions. Genetics has significantly changed the understanding of disease, identifying unexpected genetic predispositions to conditions such as age-related macular degeneration (AMD), which opens up new opportunities for targeted interventions.']}], 'duration': 933.618, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI1605023.jpg', 'highlights': ['Heart disease ranks as the top cause of death in the US, resulting in 650,000 deaths annually, highlighting its significant impact on mortality.', "COVID-19 has had a substantial impact on well-being, affecting millions of Americans' ability to work and have a support network, underscoring the disease's significance in terms of lifestyle impact.", 'Cancer is highlighted as the second leading cause of mortality, emphasizing its considerable impact on the population with 600,000 deaths per year.', 'The availability of healthy food and societal interventions can potentially address the impact of diseases like obesity and diabetes, emphasizing the potential for societal changes to mitigate the impact of certain diseases.', "Understanding genetics can influence the mechanism to counteract environmental components, potentially decreasing the impact of diseases like Alzheimer's.", 'Genes with minimal variation but no association with disease can be considered developmental genes, providing insights into the importance of genes based on their variation and disease association.', "Genetics can be utilized to manipulate metabolic processes to counteract environmental influences, as demonstrated by the analogy of obesity as a 'bathtub of fat.'", 'Mammals have evolved mechanisms for fail fast in early embryonic development, with an enormous investment in resources for newborns, contributing to a good evolutionary principle.', 'Understanding genetic mutations and their impact on disease can guide pharmaceutical intervention, offering new possibilities for treatment.', 'Genetics has significantly changed the understanding of disease, identifying unexpected genetic predispositions to conditions such as age-related macular degeneration (AMD), which opens up new opportunities for targeted interventions.']}, {'end': 3660.569, 'segs': [{'end': 2676.408, 'src': 'embed', 'start': 2540.731, 'weight': 0, 'content': [{'end': 2545.454, 'text': 'I mean, philosophically speaking is a pretty powerful thing to live with.', 'start': 2540.731, 'duration': 4.723}, {'end': 2549.316, 'text': "Maybe that's so we agreed to talk again, by the way,", 'start': 2546.314, 'duration': 3.002}, {'end': 2555.919, 'text': "for the listeners to where we're gonna try to focus on science today and a little bit of philosophy next time.", 'start': 2549.316, 'duration': 6.603}, {'end': 2565.985, 'text': "but it's interesting to think about the more you're able to know about yourself from the genetic information in terms of the diseases,", 'start': 2555.919, 'duration': 10.066}, {'end': 2568.086, 'text': 'how that changes your own view of life.', 'start': 2565.985, 'duration': 2.101}, {'end': 2570.547, 'text': "yeah, so there's.", 'start': 2568.726, 'duration': 1.821}, {'end': 2578.734, 'text': "there's a lot of impact there and there's a something called genetics exceptionalism, which basically thinks of genetics as something very,", 'start': 2570.547, 'duration': 8.187}, {'end': 2583.958, 'text': 'very different than everything else, as a type of determinism.', 'start': 2578.734, 'duration': 5.224}, {'end': 2587.28, 'text': "and um, you know, let's talk about that next time.", 'start': 2583.958, 'duration': 3.322}, {'end': 2588.861, 'text': "so basically, it's a good preview.", 'start': 2587.28, 'duration': 1.581}, {'end': 2591.624, 'text': "yeah, so let's go back to amd.", 'start': 2588.861, 'duration': 2.763}, {'end': 2595.507, 'text': 'so basically, with amd we have no idea what causes amd.', 'start': 2591.624, 'duration': 3.883}, {'end': 2602.957, 'text': 'you know, it was a mystery until the genetics were worked out.', 'start': 2596.874, 'duration': 6.083}, {'end': 2609.92, 'text': 'And now the fact that I know that I have a predisposition allows me to sort of make some life choices, number one.', 'start': 2603.657, 'duration': 6.263}, {'end': 2617.044, 'text': 'But number two, the genes that lead to that predisposition give us insights as to how does it actually work.', 'start': 2610.481, 'duration': 6.563}, {'end': 2622.186, 'text': "And that's a place where genetics gave us something totally unexpected.", 'start': 2618.424, 'duration': 3.762}, {'end': 2635.065, 'text': "So there's a complement pathway which is an immune function pathway that was in most of the loci associated with AMD.", 'start': 2622.947, 'duration': 12.118}, {'end': 2644.071, 'text': "And that basically told us that, wow, there's an immune basis to this eye disorder that people had just not expected before.", 'start': 2635.886, 'duration': 8.185}, {'end': 2649.374, 'text': 'If you look at complement, it was recently also implicated in schizophrenia.', 'start': 2645.171, 'duration': 4.203}, {'end': 2656.441, 'text': "And there's a type of microglia that is involved in synaptic pruning.", 'start': 2651.019, 'duration': 5.422}, {'end': 2659.362, 'text': 'So synapses are the connections between neurons.', 'start': 2657.241, 'duration': 2.121}, {'end': 2667.105, 'text': 'And in this whole, use it or lose it view of mental cognition and other capabilities.', 'start': 2660.402, 'duration': 6.703}, {'end': 2676.408, 'text': 'you basically have microglia, which are immune cells that are sort of constantly traversing your brain and then pruning neuronal connections,', 'start': 2667.105, 'duration': 9.303}], 'summary': "Genetic information impacts life choices and reveals unexpected insights, e.g. amd's immune basis.", 'duration': 135.677, 'max_score': 2540.731, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI2540731.jpg'}, {'end': 2720.687, 'src': 'embed', 'start': 2697.154, 'weight': 6, 'content': [{'end': 2703.857, 'text': 'Of course we knew it has to do with neurons, but the role of the complement complex, which is also implicated in AMD,', 'start': 2697.154, 'duration': 6.703}, {'end': 2706.257, 'text': 'which is now also implicated in schizophrenia, was a huge surprise.', 'start': 2703.857, 'duration': 2.4}, {'end': 2714.946, 'text': "What's the complement complex? So it's basically a set of genes, the complement genes, that are basically having various immune roles.", 'start': 2706.377, 'duration': 8.569}, {'end': 2720.687, 'text': 'And as I was saying earlier, our immune system has been co-opted for many different roles across the body.', 'start': 2715.386, 'duration': 5.301}], 'summary': 'Complement complex implicated in amd and schizophrenia, surprising role in immune system.', 'duration': 23.533, 'max_score': 2697.154, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI2697154.jpg'}, {'end': 2878.19, 'src': 'embed', 'start': 2808.71, 'weight': 7, 'content': [{'end': 2814.593, 'text': 'But basically we were for the first time able to show that specific chromatin states, specific epigenomic states.', 'start': 2808.71, 'duration': 5.883}, {'end': 2819.935, 'text': 'in that case, enhancers were in fact enriched in disease-associated variants.', 'start': 2814.593, 'duration': 5.342}, {'end': 2831.266, 'text': 'We push that further in the Ernst Nature paper a year later, and then in this roadmap epigenomics paper a few years after that.', 'start': 2820.683, 'duration': 10.583}, {'end': 2840.109, 'text': 'But basically, that matrix that you mentioned earlier was in fact the first time that we could see what genetic traits have,', 'start': 2831.307, 'duration': 8.802}, {'end': 2844.811, 'text': 'genetic variants that are enriched in what tissues in the body.', 'start': 2840.109, 'duration': 4.702}, {'end': 2848.539, 'text': 'And a lot of that map made complete sense.', 'start': 2846.297, 'duration': 2.242}, {'end': 2854.885, 'text': 'If you looked at a diversity of immune traits like allergies and type 1 diabetes, and so on and so forth,', 'start': 2848.82, 'duration': 6.065}, {'end': 2856.987, 'text': 'you basically could see that they were enriching,', 'start': 2854.885, 'duration': 2.102}, {'end': 2868.047, 'text': 'that the genetic variants associated with those traits were enriched in enhancers in these gene regulatory elements active in T cells and B cells and hematopoietic stem cells,', 'start': 2857.984, 'duration': 10.063}, {'end': 2868.627, 'text': 'and so on and so forth.', 'start': 2868.047, 'duration': 0.58}, {'end': 2878.19, 'text': 'So that basically gave us confirmation in many ways that those immune traits were indeed enriching in immune cells.', 'start': 2869.247, 'duration': 8.943}], 'summary': 'Epigenomic states revealed enrichments in disease-associated variants, confirming the association of immune traits with specific genetic variants in immune cells.', 'duration': 69.48, 'max_score': 2808.71, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI2808710.jpg'}, {'end': 3190.226, 'src': 'embed', 'start': 3161.082, 'weight': 10, 'content': [{'end': 3163.606, 'text': 'I was able indeed to reverse these processes in mice.', 'start': 3161.082, 'duration': 2.524}, {'end': 3172.353, 'text': "Can I do the same thing in humans? So the knowledge of the tissues gives you the pathway to treatment, but that's not the only part.", 'start': 3164.006, 'duration': 8.347}, {'end': 3176.416, 'text': 'There are many additional steps to figuring out the mechanism of disease.', 'start': 3172.714, 'duration': 3.702}, {'end': 3178.358, 'text': "I mean, so that's really promising.", 'start': 3176.436, 'duration': 1.922}, {'end': 3181.76, 'text': 'Maybe take a small step back.', 'start': 3178.898, 'duration': 2.862}, {'end': 3190.226, 'text': "You've mentioned all these puzzles that were figured out with the Nature paper for, I mean, you've mentioned a ton of diseases.", 'start': 3182.22, 'duration': 8.006}], 'summary': 'Researcher reversed processes in mice, now aims for human treatment. promising progress in understanding disease mechanisms.', 'duration': 29.144, 'max_score': 3161.082, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI3161082.jpg'}, {'end': 3292.532, 'src': 'embed', 'start': 3229.579, 'weight': 11, 'content': [{'end': 3240.385, 'text': 'Why was that even a case? Because the advent of DNA and the genome and the central dogma of DNA makes RNA makes protein in many ways unified biology.', 'start': 3229.579, 'duration': 10.806}, {'end': 3252.112, 'text': 'you could suddenly study the process of transcription in viruses or in bacteria and have a huge impact on yeast and fly, and maybe even mammals,', 'start': 3241.584, 'duration': 10.528}, {'end': 3256.035, 'text': 'because of this realization of these common underlying processes.', 'start': 3252.112, 'duration': 3.923}, {'end': 3266.143, 'text': 'And in the same way that DNA unified biology, genetics is unifying disease studies.', 'start': 3257.576, 'duration': 8.567}, {'end': 3268.104, 'text': 'So you used to have.', 'start': 3267.144, 'duration': 0.96}, {'end': 3282.109, 'text': "you used to have, I don't know, cardiovascular disease department and neurological disease department and neurodegeneration department,", 'start': 3271.162, 'duration': 10.947}, {'end': 3288.012, 'text': 'and basically immune and cancer, and so on and so forth.', 'start': 3282.109, 'duration': 5.903}, {'end': 3292.532, 'text': 'And all of these were studied in different labs you know, because it made sense.', 'start': 3288.333, 'duration': 4.199}], 'summary': 'Dna and genetics unified biology, revolutionizing disease studies.', 'duration': 62.953, 'max_score': 3229.579, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI3229579.jpg'}, {'end': 3492.595, 'src': 'embed', 'start': 3465.174, 'weight': 13, 'content': [{'end': 3473.741, 'text': "you cannot be a specialist anymore if you're a genomicist, you have to be a specialist in every single disorder.", 'start': 3465.174, 'duration': 8.567}, {'end': 3483.489, 'text': 'and the reason for that is that the fundamental understanding of the circuitry of the human genome that you need to solve schizophrenia,', 'start': 3473.741, 'duration': 9.748}, {'end': 3489.113, 'text': "That fundamental circuitry, is hugely important to solve Alzheimer's.", 'start': 3484.89, 'duration': 4.223}, {'end': 3492.595, 'text': 'And that same circuitry is hugely important to solve metabolic disorders.', 'start': 3489.513, 'duration': 3.082}], 'summary': 'Genomicists must specialize in every disorder due to the fundamental circuitry of the human genome being crucial for solving various conditions.', 'duration': 27.421, 'max_score': 3465.174, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI3465174.jpg'}, {'end': 3588.584, 'src': 'embed', 'start': 3558.926, 'weight': 14, 'content': [{'end': 3561.887, 'text': "So that's sort of the current structure of my group, if you wish.", 'start': 3558.926, 'duration': 2.961}, {'end': 3565.389, 'text': "So basically what we're doing is focusing on the fundamental circuitry.", 'start': 3562.267, 'duration': 3.122}, {'end': 3576.772, 'text': "But at the same time, we're the users of our own tools by collaborating with many other labs in every one of these disorders that we mentioned.", 'start': 3567.079, 'duration': 9.693}, {'end': 3583.582, 'text': 'We basically have a heart focus on cardiovascular disease, coronary artery disease, heart failure, and so on and so forth.', 'start': 3577.433, 'duration': 6.149}, {'end': 3588.584, 'text': 'We have an immune focus on several immune disorders.', 'start': 3584.222, 'duration': 4.362}], 'summary': 'Group focuses on fundamental circuitry, with a heart focus on cardiovascular disease and an immune focus on several immune disorders.', 'duration': 29.658, 'max_score': 3558.926, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI3558926.jpg'}], 'start': 2540.731, 'title': 'Genetics, immune system, and disease connections', 'summary': 'Discusses the impact of genetic information on self-view and life choices, the unexpected role of the immune system in neurological disorders, and how genetics is unifying disease studies, providing insights into potential therapeutic pathways for treatment and the breakdown of traditional departmental boundaries.', 'chapters': [{'end': 2649.374, 'start': 2540.731, 'title': 'Genetics and philosophy impact', 'summary': 'Discusses the impact of genetic information on self-view and life choices, highlighting the unexpected insights into diseases like amd through genetics, including the immune basis of the disorder and its implications in schizophrenia.', 'duration': 108.643, 'highlights': ["The complement pathway's association with AMD provided unexpected insights into the immune basis of the disorder, revealing a new understanding of the disease.", 'Understanding genetic predisposition allows for making informed life choices and gaining insights into disease mechanisms, positively impacting self-view and health decisions.', 'Genetics exceptionalism, viewing genetics as a unique form of determinism, raises philosophical questions about its impact on life and self-perception.', 'The mystery of AMD was solved through genetics, providing a new understanding of the disease and enabling individuals to make life choices based on predisposition.', 'The genetic predisposition to AMD and its associated genes offer insights into disease mechanisms, highlighting the interplay of genetics and immune function in AMD and its implications in other disorders like schizophrenia.']}, {'end': 3205.436, 'start': 2651.019, 'title': "Immune system's role in neurological disorders", 'summary': "Explores the unexpected role of the immune system, particularly microglia, in synaptic pruning and its impact on neurological disorders like schizophrenia, alzheimer's, and type 2 diabetes, providing insights into potential therapeutic pathways for treatment.", 'duration': 554.417, 'highlights': ["Microglia's involvement in synaptic pruning and its impact on schizophrenia Microglia, immune cells responsible for pruning unused synaptic connections, are implicated in the altered synaptic pruning process in schizophrenia, potentially leading to an increased risk of the disorder.", "Complement complex's role in neurological disorders The complement complex, known for its immune functions, is unexpectedly linked to neurological disorders such as AMD and schizophrenia, providing new insights into the immune system's involvement in these conditions.", 'Utilizing epigenomic maps to identify disease-associated genetic variants The comprehensive epigenomic maps of human tissues enable the identification of active gene regulatory elements and the association of disease-linked genetic loci with specific tissues, offering valuable insights into the genetic basis of various disorders.', 'Enrichment of genetic variants in specific tissues and its implications for disease traits The enrichment of genetic variants associated with traits like blood pressure, height, and inflammatory bowel disease in specific tissues provides valuable insights into the tissue-specific mechanisms underlying these conditions and potential therapeutic targets.', 'Implications of tissue-specific enrichment for therapeutic development Understanding the tissue-specific enrichment of genetic variants offers a pathway for targeted therapeutic development, enabling the screening of molecules directly impacting the identified pathways in specific cell types, ultimately leading to potential clinical trials and treatment strategies.', 'Importance of tissue-specific knowledge for therapeutic pathway and mechanism of disease The knowledge of tissue-specific involvement in disorders provides crucial insights into the pathway for treatment development and understanding the underlying mechanisms, essential for identifying potential therapeutic targets and developing effective treatment strategies.']}, {'end': 3660.569, 'start': 3205.837, 'title': 'Genetics unifying disease studies', 'summary': 'Discusses how genetics is unifying disease studies by revealing unexpected connections, leading to the breakdown of traditional departmental boundaries, and the need for specialists to focus on the fundamental circuitry common to all diseases.', 'duration': 454.732, 'highlights': ['Genetics unifies disease studies by revealing unexpected connections, breaking down traditional departmental boundaries, and requiring specialists to focus on the fundamental circuitry common to all diseases. Genetics unifies disease studies; reveals unexpected connections; breaks down traditional departmental boundaries; requires specialists to focus on the fundamental circuitry common to all diseases.', 'The advent of DNA and the genome has unified biology, allowing the study of common underlying processes and impacting various organisms. Advent of DNA and the genome unifies biology; allows study of common underlying processes; impacts various organisms.', 'Genetics has led to the need for specialists to focus on the fundamental circuitry common to all diseases, necessitating collaboration across different disease areas. Genetics necessitates focus on fundamental circuitry common to all diseases; requires collaboration across different disease areas.', 'The chapter emphasizes the importance of unifying disease studies and the need for specialists to focus on the fundamental circuitry common to all diseases. Emphasizes importance of unifying disease studies; highlights need for specialists to focus on fundamental circuitry common to all diseases.']}], 'duration': 1119.838, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI2540731.jpg', 'highlights': ['Genetics exceptionalism raises philosophical questions about its impact on life and self-perception.', 'Understanding genetic predisposition allows for making informed life choices and gaining insights into disease mechanisms, positively impacting self-view and health decisions.', "The complement pathway's association with AMD provided unexpected insights into the immune basis of the disorder, revealing a new understanding of the disease.", 'The mystery of AMD was solved through genetics, providing a new understanding of the disease and enabling individuals to make life choices based on predisposition.', 'The genetic predisposition to AMD and its associated genes offer insights into disease mechanisms, highlighting the interplay of genetics and immune function in AMD and its implications in other disorders like schizophrenia.', "Microglia's involvement in synaptic pruning and its impact on schizophrenia.", "Complement complex's role in neurological disorders.", 'Utilizing epigenomic maps to identify disease-associated genetic variants.', 'Enrichment of genetic variants in specific tissues and its implications for disease traits.', 'Implications of tissue-specific enrichment for therapeutic development.', 'Importance of tissue-specific knowledge for therapeutic pathway and mechanism of disease.', 'Genetics unifies disease studies by revealing unexpected connections, breaking down traditional departmental boundaries, and requiring specialists to focus on the fundamental circuitry common to all diseases.', 'The advent of DNA and the genome has unified biology, allowing the study of common underlying processes and impacting various organisms.', 'Genetics has led to the need for specialists to focus on the fundamental circuitry common to all diseases, necessitating collaboration across different disease areas.', 'The chapter emphasizes the importance of unifying disease studies and the need for specialists to focus on the fundamental circuitry common to all diseases.']}, {'end': 4788.721, 'segs': [{'end': 3731.885, 'src': 'embed', 'start': 3706.201, 'weight': 0, 'content': [{'end': 3714.828, 'text': 'How do you link regulators to enhancers and enhancers to their target genes using epigenomics and regulatory genomics?', 'start': 3706.201, 'duration': 8.627}, {'end': 3724.757, 'text': "So through the years we've basically built all this infrastructure for understanding what I like to say every single nucleotide of the human genome.", 'start': 3715.209, 'duration': 9.548}, {'end': 3730.163, 'text': 'and how it acts in every one of the major cell types and tissues of the human body.', 'start': 3725.297, 'duration': 4.866}, {'end': 3731.885, 'text': 'I mean, this is no small task.', 'start': 3730.483, 'duration': 1.402}], 'summary': 'Using epigenomics and regulatory genomics to link regulators to enhancers and their target genes in every major cell type and tissue of the human body.', 'duration': 25.684, 'max_score': 3706.201, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI3706201.jpg'}, {'end': 3849.582, 'src': 'embed', 'start': 3820.912, 'weight': 5, 'content': [{'end': 3826.454, 'text': 'The traditional view of biology was you have one postdoc working on this gene and another postdoc working on that gene.', 'start': 3820.912, 'duration': 5.542}, {'end': 3829.675, 'text': "And they'll just figure out everything about that gene.", 'start': 3827.555, 'duration': 2.12}, {'end': 3830.936, 'text': "And that's their job.", 'start': 3830.316, 'duration': 0.62}, {'end': 3835.897, 'text': "what we've realized is how polygenic the diseases are.", 'start': 3831.996, 'duration': 3.901}, {'end': 3838.098, 'text': "So we can't have one postdoc per gene anymore.", 'start': 3836.278, 'duration': 1.82}, {'end': 3843.36, 'text': 'We now have to have these cross-cutting needs.', 'start': 3838.158, 'duration': 5.202}, {'end': 3849.582, 'text': "And I'm gonna describe the path to circuitry along those needs.", 'start': 3844.14, 'duration': 5.442}], 'summary': 'Biology has shifted to studying polygenic diseases, requiring cross-cutting approaches.', 'duration': 28.67, 'max_score': 3820.912, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI3820912.jpg'}, {'end': 4117.865, 'src': 'embed', 'start': 4084.205, 'weight': 4, 'content': [{'end': 4094.47, 'text': 'And what we found is that this FTO locus, even though it is associated with obesity, does not implicate the FTO gene.', 'start': 4084.205, 'duration': 10.265}, {'end': 4106.312, 'text': 'The genetic variant sits in the first intron of the FTO gene, but it controls two genes, IRX3 and IRX5,', 'start': 4096.621, 'duration': 9.691}, {'end': 4111.497, 'text': 'that are sitting 1.2 million nucleotides away, several genes away.', 'start': 4106.312, 'duration': 5.185}, {'end': 4113.581, 'text': 'Oh boy.', 'start': 4113.2, 'duration': 0.381}, {'end': 4115.843, 'text': 'What am I supposed to feel about that?', 'start': 4113.6, 'duration': 2.243}, {'end': 4117.865, 'text': "Because isn't that like super complicated then?", 'start': 4115.863, 'duration': 2.002}], 'summary': 'Fto locus linked to obesity, controls irx3 and irx5 genes 1.2m nucleotides away.', 'duration': 33.66, 'max_score': 4084.205, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI4084205.jpg'}, {'end': 4190.867, 'src': 'embed', 'start': 4163.224, 'weight': 3, 'content': [{'end': 4169.872, 'text': 'how every genetic variant impacts the expression of every gene in every tissue imaginable across hundreds of individuals.', 'start': 4163.224, 'duration': 6.648}, {'end': 4179.459, 'text': 'And then you now have one of the building blocks, not even all of the building blocks, for then going and understanding disease.', 'start': 4170.814, 'duration': 8.645}, {'end': 4184.542, 'text': 'Okay So embrace the wholeness of the circuitry.', 'start': 4179.6, 'duration': 4.942}, {'end': 4190.867, 'text': 'Correct So back to the question of starting knowing nothing to the disease and going to the treatment.', 'start': 4184.723, 'duration': 6.144}], 'summary': "Understanding genetic variants' impact on gene expression across hundreds of individuals is crucial for comprehending and treating diseases.", 'duration': 27.643, 'max_score': 4163.224, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI4163224.jpg'}, {'end': 4234.529, 'src': 'embed', 'start': 4206.732, 'weight': 6, 'content': [{'end': 4217.942, 'text': 'And the reason for that, you know, thankfully, is that there is convergence, that the same processes are impacted in different ways by different loci.', 'start': 4206.732, 'duration': 11.21}, {'end': 4222.647, 'text': "And that's a saving grace for our field.", 'start': 4219.364, 'duration': 3.283}, {'end': 4230.515, 'text': "The fact that if I look at hundreds of genetic variants associated with Alzheimer's, they localize in a small number of processes.", 'start': 4223.067, 'duration': 7.448}, {'end': 4234.529, 'text': "Can you clarify why that's hopeful?", 'start': 4231.806, 'duration': 2.723}], 'summary': "Hundreds of genetic variants for alzheimer's localize in a small number of processes, providing hope for convergence in the field.", 'duration': 27.797, 'max_score': 4206.732, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI4206732.jpg'}, {'end': 4435.431, 'src': 'embed', 'start': 4398.435, 'weight': 7, 'content': [{'end': 4399.516, 'text': 'how do you do that?', 'start': 4398.435, 'duration': 1.081}, {'end': 4403.46, 'text': 'you basically have all of the genetic variants associated with the disorder.', 'start': 4399.516, 'duration': 3.944}, {'end': 4408.965, 'text': "And then you're asking for all of the enhancers active in a particular tissue.", 'start': 4403.96, 'duration': 5.005}, {'end': 4413.508, 'text': "For 540 disorders, we've basically found that indeed there is an enrichment.", 'start': 4409.145, 'duration': 4.363}, {'end': 4416.311, 'text': 'That basically means that there is commonality.', 'start': 4413.668, 'duration': 2.643}, {'end': 4419.854, 'text': 'And from the commonality, we can just get insights.', 'start': 4416.991, 'duration': 2.863}, {'end': 4425.922, 'text': "So to explain in mathematical terms, We're basically building an empirical prior.", 'start': 4420.574, 'duration': 5.348}, {'end': 4435.431, 'text': "We're using a Bayesian approach to basically say, great, all of these variants are equally likely in a particular locus to be important.", 'start': 4427.023, 'duration': 8.408}], 'summary': 'Identifying genetic variants for 540 disorders, finding enrichment, and using a bayesian approach to determine likelihood.', 'duration': 36.996, 'max_score': 4398.435, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI4398435.jpg'}, {'end': 4582.945, 'src': 'embed', 'start': 4559.829, 'weight': 8, 'content': [{'end': 4567.914, 'text': "So even though there are 6 million variants, there are 6 million loci, there's, you know, this variation is inherited in blocks.", 'start': 4559.829, 'duration': 8.085}, {'end': 4573.759, 'text': 'And every one of these blocks has like two dozen genetic variants that are all associated.', 'start': 4569.617, 'duration': 4.142}, {'end': 4582.945, 'text': "So in the case of FTO, it wasn't just one variant, it was 89 common variants that were all humongously associated with obesity.", 'start': 4574.14, 'duration': 8.805}], 'summary': '6 million loci with 89 common variants associated with obesity.', 'duration': 23.116, 'max_score': 4559.829, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI4559829.jpg'}, {'end': 4699.125, 'src': 'embed', 'start': 4672.799, 'weight': 9, 'content': [{'end': 4681.023, 'text': 'And if you go further down the lineage of your fat, you basically have your white fat cells, These are the cells that store energy.', 'start': 4672.799, 'duration': 8.224}, {'end': 4687.107, 'text': "So when you eat a lot, but you don't exercise too much, there's an excess set of calories, excess energy.", 'start': 4681.564, 'duration': 5.543}, {'end': 4688.208, 'text': 'What do you do with those??', 'start': 4687.527, 'duration': 0.681}, {'end': 4689.949, 'text': 'You basically create.', 'start': 4688.588, 'duration': 1.361}, {'end': 4699.125, 'text': 'you spend a lot of that energy to create these high energy molecules lipids which you can then burn when you need them on a rainy day.', 'start': 4689.949, 'duration': 9.176}], 'summary': 'White fat cells store excess energy as lipids for future use.', 'duration': 26.326, 'max_score': 4672.799, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI4672799.jpg'}], 'start': 3661.451, 'title': 'Genome analysis and disease circuitry', 'summary': 'Emphasizes the importance of understanding the human genome and its function through profiling the epigenome, and discusses the complexity of disease genetics, emphasizing the need to understand genetic circuitry and epigenomic enrichments, with insights into genetic variants impacting various disorders.', 'chapters': [{'end': 3731.885, 'start': 3661.451, 'title': 'Genome analysis and functional mapping', 'summary': 'Highlights the importance of understanding every single nucleotide of the human genome and its function in major cell types and tissues through profiling the epigenome using comparative genomics and regulatory genomics, emphasizing the infrastructure built for this purpose.', 'duration': 70.434, 'highlights': ['The infrastructure built for understanding every single nucleotide of the human genome and its function in major cell types and tissues, emphasizing the comprehensive nature of the task.', 'The focus on profiling the epigenome using comparative genomics and finding important nucleotides in the genome, highlighting the approach taken for understanding gene regulation.', 'The emphasis on finding human genes and gene regulatory elements using comparative genomics, showcasing the process of identifying essential genetic components.', 'The process of linking regulators to enhancers and enhancers to their target genes using epigenomics and regulatory genomics, demonstrating the integrated approach for understanding gene regulation.']}, {'end': 4206.132, 'start': 3731.965, 'title': 'Understanding disease circuitry and therapeutics', 'summary': 'Discusses the complexity of disease genetics, emphasizing the need to understand genetic circuitry and epigenomic enrichments, with a focus on parallel analysis of thousands of genes and the impact of genetic variants on disease, challenging traditional postdoc-centric approaches to biology. the speaker also highlights the discovery that genetic associations with obesity do not necessarily implicate the associated gene, but may instead control genes located millions of nucleotides away, emphasizing the importance of understanding genetic circuitry in disease research.', 'duration': 474.167, 'highlights': ["The speaker emphasizes the need to understand genetic circuitry and epigenomic enrichments, with a focus on parallel analysis of thousands of genes and the impact of genetic variants on disease. The chapter discusses the speaker's group's work in understanding genetic circuitry and the impact of genetic variants on disease, which involves parallel analysis of thousands of genes and the need to understand epigenomic enrichments.", 'The discovery that genetic associations with obesity do not necessarily implicate the associated gene, but may instead control genes located millions of nucleotides away, highlighting the importance of understanding genetic circuitry in disease research. The speaker highlights the discovery that genetic associations with obesity do not necessarily implicate the associated gene, but may instead control genes located millions of nucleotides away, emphasizing the importance of understanding genetic circuitry in disease research.', 'Challenges traditional postdoc-centric approaches to biology by emphasizing the complexity and polygenic nature of diseases, requiring cross-cutting needs and parallel analysis across thousands of genes. The speaker challenges traditional postdoc-centric approaches to biology by emphasizing the complexity and polygenic nature of diseases, requiring cross-cutting needs and parallel analysis across thousands of genes.']}, {'end': 4788.721, 'start': 4206.732, 'title': 'Genetic variants and disease convergence', 'summary': "Discusses the hopeful convergence of genetic variants impacting a small number of biological processes in various disorders, such as alzheimer's and schizophrenia, with insights from epigenomic enrichment and co-inheritance patterns.", 'duration': 581.989, 'highlights': ["The convergence of genetic variants impacting a small number of biological processes in various disorders provides hope for understanding diseases like Alzheimer's and schizophrenia. Alzheimer's is associated with about 10 different types of processes, including lipid metabolism, immune cell function, and neuronal energetics.", 'Insights from epigenomic enrichment reveal commonality across 540 disorders, leading to a Bayesian approach for understanding the importance of genetic variants in particular loci. Epigenomic enrichment has been found for every single disease studied, indicating commonality and providing valuable insights.', 'Co-inheritance patterns and crossover events during meiosis lead to the inheritance of variation in blocks, with specific genetic variants being associated with diseases like obesity. For obesity, 89 common variants were found to be significantly associated, enriching in the same epigenomic map for mesenchymal stem cells.', 'The differentiation of progenitor cells into various lineages, including fat cells, reveals insights into the storage and burning of energy, with 42% of European chromosomes having a predisposition to storing fat. Progenitor cells give rise to white fat cells that store excess energy, contributing to obesity if not balanced with exercise.']}], 'duration': 1127.27, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI3661451.jpg', 'highlights': ['The infrastructure built for understanding every single nucleotide of the human genome and its function in major cell types and tissues, emphasizing the comprehensive nature of the task.', 'The focus on profiling the epigenome using comparative genomics and finding important nucleotides in the genome, highlighting the approach taken for understanding gene regulation.', 'The process of linking regulators to enhancers and enhancers to their target genes using epigenomics and regulatory genomics, demonstrating the integrated approach for understanding gene regulation.', 'The speaker emphasizes the need to understand genetic circuitry and epigenomic enrichments, with a focus on parallel analysis of thousands of genes and the impact of genetic variants on disease.', 'The discovery that genetic associations with obesity do not necessarily implicate the associated gene, but may instead control genes located millions of nucleotides away, highlighting the importance of understanding genetic circuitry in disease research.', 'Challenges traditional postdoc-centric approaches to biology by emphasizing the complexity and polygenic nature of diseases, requiring cross-cutting needs and parallel analysis across thousands of genes.', "The convergence of genetic variants impacting a small number of biological processes in various disorders provides hope for understanding diseases like Alzheimer's and schizophrenia.", 'Insights from epigenomic enrichment reveal commonality across 540 disorders, leading to a Bayesian approach for understanding the importance of genetic variants in particular loci.', 'Co-inheritance patterns and crossover events during meiosis lead to the inheritance of variation in blocks, with specific genetic variants being associated with diseases like obesity.', 'The differentiation of progenitor cells into various lineages, including fat cells, reveals insights into the storage and burning of energy, with 42% of European chromosomes having a predisposition to storing fat.']}, {'end': 5466.464, 'segs': [{'end': 4820.514, 'src': 'embed', 'start': 4788.721, 'weight': 0, 'content': [{'end': 4797.725, 'text': 'genetic variants associated with obesity across many of these regions were all enriched repeatedly in mesenchymal stem cell enhancers.', 'start': 4788.721, 'duration': 9.004}, {'end': 4805.129, 'text': 'So that gave us a hint as to which of these genetic variants was likely driving this whole association.', 'start': 4798.326, 'duration': 6.803}, {'end': 4809.683, 'text': 'And we ended up with this one genetic variant called RS1421085.', 'start': 4805.939, 'duration': 3.744}, {'end': 4820.514, 'text': 'And that genetic variant out of the 89 was the one that we predicted to be causal for the disease.', 'start': 4814.389, 'duration': 6.125}], 'summary': 'Genetic variant rs1421085 predicted as causal for obesity.', 'duration': 31.793, 'max_score': 4788.721, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI4788721.jpg'}, {'end': 4871.962, 'src': 'embed', 'start': 4839.648, 'weight': 1, 'content': [{'end': 4841.509, 'text': 'these boundaries of these inherited blocks.', 'start': 4839.648, 'duration': 1.861}, {'end': 4843.289, 'text': "That's the second step.", 'start': 4842.529, 'duration': 0.76}, {'end': 4852.492, 'text': 'The third step is once you know that causal variant, try to figure out what is the motif that is disrupted by that causal variant.', 'start': 4843.909, 'duration': 8.583}, {'end': 4858.794, 'text': "Basically, how does it act? Variants don't just disrupt elements, they disrupt the binding of specific regulators.", 'start': 4852.512, 'duration': 6.282}, {'end': 4867.019, 'text': 'So, basically, the third step there was how do you find the motif that is responsible, like the gene regulatory word,', 'start': 4859.474, 'duration': 7.545}, {'end': 4871.962, 'text': 'the building block of gene regulation, that is responsible for that dysregulatory event?', 'start': 4867.019, 'duration': 4.943}], 'summary': 'Identifying causal variants and disrupted motifs for gene regulation.', 'duration': 32.314, 'max_score': 4839.648, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI4839648.jpg'}, {'end': 5008.684, 'src': 'embed', 'start': 4985.317, 'weight': 4, 'content': [{'end': 4993.34, 'text': 'How?? By basically doing perturbation experiments, or by looking at the folding of the epigenome,', 'start': 4985.317, 'duration': 8.023}, {'end': 4998.421, 'text': 'or by looking at the genetic impact of that genetic variant on the expression of genes.', 'start': 4993.34, 'duration': 5.081}, {'end': 5000.222, 'text': 'And we use all three.', 'start': 4999.361, 'duration': 0.861}, {'end': 5002.302, 'text': 'So let me go through them.', 'start': 5001.502, 'duration': 0.8}, {'end': 5005.363, 'text': 'Basically, one of them is physical links.', 'start': 5002.542, 'duration': 2.821}, {'end': 5008.684, 'text': 'This is the folding of the genome onto itself.', 'start': 5006.263, 'duration': 2.421}], 'summary': 'Research involves perturbation experiments, epigenome folding, and genetic impact on gene expression.', 'duration': 23.367, 'max_score': 4985.317, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI4985317.jpg'}, {'end': 5202.984, 'src': 'embed', 'start': 5174.095, 'weight': 6, 'content': [{'end': 5175.375, 'text': "That's step one of the physical.", 'start': 5174.095, 'duration': 1.28}, {'end': 5183.719, 'text': 'And what the physical revealed is topologically associated domains, basically big blocks of the genome that are topologically connected together.', 'start': 5175.715, 'duration': 8.004}, {'end': 5185.419, 'text': "That's the physical.", 'start': 5184.919, 'duration': 0.5}, {'end': 5188.641, 'text': 'The second one is the genetic links.', 'start': 5186.26, 'duration': 2.381}, {'end': 5198.563, 'text': 'It basically says across individuals that have different genetic variants, how are their genes expressed differently?', 'start': 5190.021, 'duration': 8.542}, {'end': 5202.984, 'text': 'Remember before I was saying that the path between genetics and disease is enormous,', 'start': 5199.123, 'duration': 3.861}], 'summary': 'Physical exam identified topologically associated domains in the genome. genetic links explore gene expression across individuals with different variants.', 'duration': 28.889, 'max_score': 5174.095, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI5174095.jpg'}, {'end': 5337.817, 'src': 'embed', 'start': 5308.025, 'weight': 5, 'content': [{'end': 5317.949, 'text': 'you can basically take a guide RNA that you put into the CRISPR system and the CRISPR system will basically use this guide RNA scan the genome,', 'start': 5308.025, 'duration': 9.924}, {'end': 5321.19, 'text': "find wherever there's a match and then cut the genome.", 'start': 5317.949, 'duration': 3.241}, {'end': 5327.252, 'text': "So, you know, I digress, but it's a bacterial immune defense system.", 'start': 5322.51, 'duration': 4.742}, {'end': 5337.817, 'text': 'So, basically, bacteria are constantly attacked by viruses, But sometimes they win against the viruses and they chop up these viruses and remember,', 'start': 5327.933, 'duration': 9.884}], 'summary': 'Crispr system uses guide rna to scan and cut genome, a bacterial immune defense system.', 'duration': 29.792, 'max_score': 5308.025, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI5308025.jpg'}], 'start': 4788.721, 'title': 'Genetic impact on obesity', 'summary': 'Discusses the identification of a causal genetic variant, rs1421085, associated with obesity, and explores genome folding using perturbation experiments and epigenetic analysis, with a focus on crispr technology and its co-opted use in genetic research.', 'chapters': [{'end': 4984.637, 'start': 4788.721, 'title': 'Genetic variants and obesity', 'summary': 'Discusses the identification of a causal genetic variant, rs1421085, associated with obesity through a multi-step process involving tissue enrichment, causal variant identification, motif disruption analysis, regulator identification, and potential therapeutic intervention.', 'duration': 195.916, 'highlights': ['The genetic variant RS1421085 was predicted to be causal for obesity out of 89 variants, indicating its significance in driving the association.', 'The multi-step process involves identifying the relevant tissue, causal variant, disrupted motif and upstream regulator, and potential target genes, providing a comprehensive approach to understanding and potentially intervening in obesity genetics.', 'Understanding the motif disrupted by the causal variant can lead to the identification of the regulator that is no longer able to bind, providing insights into potential therapeutic targets for obesity intervention.', 'The process ultimately aims to develop pharmaceutical therapeutics or other interventions that affect the expression of the gene associated with the causal variant, potentially offering new approaches for addressing obesity at a genetic level.']}, {'end': 5466.464, 'start': 4985.317, 'title': 'Studying genome folding and genetic impact', 'summary': 'Delves into the exploration of genome folding using perturbation experiments and epigenetic analysis, uncovering physical and genetic links, with a focus on crispr technology and its co-opted use in genetic research.', 'duration': 481.147, 'highlights': ['The use of perturbation experiments, epigenetic analysis, and physical links to study genome folding. The chapter discusses the use of perturbation experiments, epigenetic analysis, and physical links to study the folding of the epigenome and the impact of genetic variants on gene expression.', "The explanation of the CRISPR system's bacterial immune defense and its co-opted use as a genetic research tool. An in-depth explanation of the CRISPR system's bacterial immune defense and its co-opted use in genetic research is provided, including its RNA-guided DNA cutting mechanism and its origin from the bacterial adaptive immune response.", 'The concept of topologically associated domains and their discovery through physical links. The discovery and significance of topologically associated domains through physical links and their role in revealing big blocks of the genome that are topologically connected together.']}], 'duration': 677.743, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI4788721.jpg', 'highlights': ['The genetic variant RS1421085 was predicted to be causal for obesity out of 89 variants, indicating its significance in driving the association.', 'Understanding the motif disrupted by the causal variant can lead to the identification of the regulator that is no longer able to bind, providing insights into potential therapeutic targets for obesity intervention.', 'The multi-step process involves identifying the relevant tissue, causal variant, disrupted motif and upstream regulator, and potential target genes, providing a comprehensive approach to understanding and potentially intervening in obesity genetics.', 'The process ultimately aims to develop pharmaceutical therapeutics or other interventions that affect the expression of the gene associated with the causal variant, potentially offering new approaches for addressing obesity at a genetic level.', 'The use of perturbation experiments, epigenetic analysis, and physical links to study genome folding.', "The explanation of the CRISPR system's bacterial immune defense and its co-opted use as a genetic research tool.", 'The concept of topologically associated domains and their discovery through physical links.']}, {'end': 6421.365, 'segs': [{'end': 5496.522, 'src': 'embed', 'start': 5468.28, 'weight': 0, 'content': [{'end': 5472.283, 'text': 'And they were studying bacteria and they found that, wow, this CRISPR system is awesome.', 'start': 5468.28, 'duration': 4.003}, {'end': 5473.745, 'text': 'It allows you to defend against that.', 'start': 5472.444, 'duration': 1.301}, {'end': 5485.054, 'text': "And then it was co-opted in mammalian systems that don't use anything like that as a targeting way to basically bring these DNA cutting enzymes to any locus in the genome.", 'start': 5474.726, 'duration': 10.328}, {'end': 5489.096, 'text': 'Why would you want to cut DNA to do anything.', 'start': 5485.755, 'duration': 3.341}, {'end': 5496.522, 'text': 'The reason is that our DNA has a DNA repair mechanism where, if a region of the genome gets randomly cut,', 'start': 5489.577, 'duration': 6.945}], 'summary': 'Crispr system enables precise dna editing, enhancing genome targeting and repair mechanisms.', 'duration': 28.242, 'max_score': 5468.28, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI5468280.jpg'}, {'end': 5710.899, 'src': 'embed', 'start': 5685.648, 'weight': 1, 'content': [{'end': 5690.53, 'text': 'to basically design a set of amino acids that will target a particular sequence in your genome.', 'start': 5685.648, 'duration': 4.882}, {'end': 5696.491, 'text': 'The reason why CRISPR is amazingly, awesomely revolutionary is because,', 'start': 5691.43, 'duration': 5.061}, {'end': 5702.573, 'text': 'instead of having this team of engineers design a new set of proteins for every locus that you want to target,', 'start': 5696.491, 'duration': 6.082}, {'end': 5706.454, 'text': 'you just type it in your computer and you just synthesize an RNA guide.', 'start': 5702.573, 'duration': 3.881}, {'end': 5709.798, 'text': 'The beauty of CRISPR is not the cutting.', 'start': 5707.677, 'duration': 2.121}, {'end': 5710.899, 'text': "It's not the fixing.", 'start': 5710.038, 'duration': 0.861}], 'summary': 'Crispr allows for easy design and synthesis of rna guides for genome targeting, revolutionizing the process.', 'duration': 25.251, 'max_score': 5685.648, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI5685648.jpg'}, {'end': 6103.471, 'src': 'embed', 'start': 6076.55, 'weight': 2, 'content': [{'end': 6082.735, 'text': 'And those 13 genes are all involved in energy production, the electron transport chain.', 'start': 6076.55, 'duration': 6.185}, {'end': 6086.979, 'text': 'So basically, electrons are these massive super energy-rich molecules.', 'start': 6083.316, 'duration': 3.663}, {'end': 6092.402, 'text': 'We basically have these organelles that produce energy.', 'start': 6088.479, 'duration': 3.923}, {'end': 6097.526, 'text': 'And when your muscle exercises, you basically multiply your mitochondria.', 'start': 6093.343, 'duration': 4.183}, {'end': 6101.49, 'text': 'You basically sort of use more and more mitochondria.', 'start': 6097.747, 'duration': 3.743}, {'end': 6103.471, 'text': "And that's how you get beefed up.", 'start': 6101.91, 'duration': 1.561}], 'summary': '13 genes involved in energy production are linked to multiplying mitochondria during muscle exercise, leading to beefed-up muscles.', 'duration': 26.921, 'max_score': 6076.55, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI6076550.jpg'}, {'end': 6231.232, 'src': 'embed', 'start': 6206.697, 'weight': 3, 'content': [{'end': 6213.341, 'text': 'Thermogenesis is actually a regulatory process that modulates the third component of the thermodynamic equation.', 'start': 6206.697, 'duration': 6.644}, {'end': 6216.783, 'text': 'You can basically control thermogenesis explicitly.', 'start': 6214.001, 'duration': 2.782}, {'end': 6219.164, 'text': 'You can turn on and turn off thermogenesis.', 'start': 6217.183, 'duration': 1.981}, {'end': 6220.845, 'text': "And that's where the mitochondria comes into play.", 'start': 6219.284, 'duration': 1.561}, {'end': 6231.232, 'text': 'Exactly So RX3 and RX5 turn out to be the master regulators of a process of thermogenesis versus lipogenesis, generation of fat.', 'start': 6220.905, 'duration': 10.327}], 'summary': 'Thermogenesis can be controlled explicitly, with rx3 and rx5 as master regulators.', 'duration': 24.535, 'max_score': 6206.697, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI6206697.jpg'}, {'end': 6406.562, 'src': 'embed', 'start': 6377.279, 'weight': 4, 'content': [{'end': 6381.022, 'text': 'When you know the circuitry, you can now go crazy.', 'start': 6377.279, 'duration': 3.743}, {'end': 6383.985, 'text': 'You can now start intervening at every level.', 'start': 6381.122, 'duration': 2.863}, {'end': 6386.947, 'text': 'You can start intervening at the IRX5B level.', 'start': 6384.445, 'duration': 2.502}, {'end': 6390.69, 'text': 'You can start intervening with CRISPR-Cas9 at the single SNP level.', 'start': 6387.208, 'duration': 3.482}, {'end': 6394.294, 'text': 'You can start intervening at IRX3 and RX5 directly there.', 'start': 6391.231, 'duration': 3.063}, {'end': 6397.837, 'text': 'You can start intervening at the thermogenesis level because you know the pathway.', 'start': 6394.814, 'duration': 3.023}, {'end': 6406.562, 'text': 'You can start intervening at the differentiation level where these the decision to make either white fat or beige fat.', 'start': 6398.357, 'duration': 8.205}], 'summary': 'Understanding circuitry allows targeted interventions at multiple levels and genes, such as irx5b and irx3, with crispr-cas9 at the single snp level, and thermogenesis and differentiation levels.', 'duration': 29.283, 'max_score': 6377.279, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI6377279.jpg'}], 'start': 5468.28, 'title': 'Crispr and mitochondrial role', 'summary': "Explores the revolutionary impact of crispr technology, enabling precise dna manipulation and potential therapeutic applications. it also discusses mitochondria's role in energy production and genetic factors influencing thermogenesis, impacting energy utilization and obesity.", 'chapters': [{'end': 5638.92, 'start': 5468.28, 'title': 'Crispr: genome editing revolution', 'summary': 'Explores crispr, a revolutionary genome editing tool that allows precise dna cutting and manipulation, enabling homologous-based repair, and potential therapeutic applications, with a mention of prime editing as a recent advancement.', 'duration': 170.64, 'highlights': ['CRISPR enables precise DNA cutting and manipulation, harnessing the homologous-based repair mechanism, which explains the diploid nature of our DNA and the potential for genome editing.', 'Prime editing, a recent advancement in CRISPR technology, involves making a single-stranded break instead of a double-stranded break, allowing for local repair using a guide coupled to the initial RNA, expanding the possibilities of genome editing.', 'The chapter also addresses the potential downsides and drawbacks of CRISPR in the context of therapeutics and genetic manipulation, highlighting the need for a comprehensive understanding of its implications and applications.', "The discussion showcases the early anticipation of CRISPR's impact, with articles lauding its potential dating back to 2004, demonstrating the long-standing recognition of its revolutionary nature."]}, {'end': 5980.1, 'start': 5639.66, 'title': 'Crispr: revolutionizing genetic engineering', 'summary': 'Highlights the revolutionary impact of crispr technology, which simplifies the process of guiding cutters to target specific locations in the genome, making genetic manipulation more accessible and efficient, ultimately enabling precise gene manipulation and exploration of gene functions.', 'duration': 340.44, 'highlights': ['The beauty of CRISPR lies in its ability to simplify the guiding process of cutters to target specific locations in the genome by synthesizing an RNA guide, eliminating the need for a team of engineers and making the guiding process more accessible and efficient, ultimately revolutionizing genetic manipulation.', 'The CRISPR system, particularly CRISPR Cas9 and dead Cas9, enables the manipulation of gene expression by activating or repressing target genes, providing a powerful tool for exploring gene functions and their impact on various biological processes.', 'CRISPR technology allows for the precise targeting of enhancers and genes, enabling the exploration of gene functions and their impact on processes such as lipid metabolism and mitochondrial biogenesis, providing valuable insights into obesity and related metabolic processes.', 'The chapter emphasizes the significant impact of CRISPR technology in simplifying the process of guiding cutters to target specific locations in the genome, making genetic manipulation more accessible and efficient, ultimately enabling precise gene manipulation and exploration of gene functions.', 'The transcript explains the challenges and exciting opportunities of the field in designing different cutting technologies, highlighting the ongoing advancements in genetic engineering beyond CRISPR technology.']}, {'end': 6421.365, 'start': 5981.201, 'title': 'Mitochondria and thermogenesis', 'summary': 'Discusses the role of mitochondria in energy production and thermogenesis, the process of heat generation, and the genetic factors influencing thermogenesis, highlighting the impact on energy utilization and obesity.', 'duration': 440.164, 'highlights': ['Mitochondria are organelles responsible for energy production and multiplication, with exercise leading to the amplification of mitochondria in muscles. When muscles exercise, they multiply mitochondria to generate more energy, contributing to muscle strength and function.', 'The process of thermogenesis, regulated by RX3 and RX5, controls the generation of heat and the burning of calories, impacting energy utilization and fat storage in the body. RX3 and RX5 are master regulators of thermogenesis, influencing the burning of calories as heat and fat generation, with genetic variations affecting thermogenic capacity and energy efficiency.', 'Genetic variations in RX3 and RX5, such as the RS1421085 allele, can impact thermogenesis, leading to differences in energy utilization and susceptibility to obesity. The RS1421085 allele, affecting the binding of RX5B, can influence thermogenesis and energy utilization, potentially leading to differences in weight regulation and obesity risk.', 'Understanding the genetic circuitry associated with thermogenesis provides opportunities for intervention at multiple levels, including targeting specific genes and pathways to modulate energy utilization and fat storage. Knowledge of the genetic circuitry enables interventions at various levels, such as targeting specific genes and pathways, to modulate energy utilization and fat storage, offering potential strategies for addressing obesity and metabolic disorders.']}], 'duration': 953.085, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI5468280.jpg', 'highlights': ['CRISPR enables precise DNA cutting and manipulation, harnessing the homologous-based repair mechanism, explaining the diploid nature of our DNA and the potential for genome editing.', 'The beauty of CRISPR lies in its ability to simplify the guiding process of cutters to target specific locations in the genome by synthesizing an RNA guide, ultimately revolutionizing genetic manipulation.', 'Mitochondria are organelles responsible for energy production and multiplication, with exercise leading to the amplification of mitochondria in muscles, contributing to muscle strength and function.', 'The process of thermogenesis, regulated by RX3 and RX5, controls the generation of heat and the burning of calories, impacting energy utilization and fat storage in the body.', 'Understanding the genetic circuitry associated with thermogenesis provides opportunities for intervention at multiple levels, including targeting specific genes and pathways to modulate energy utilization and fat storage.']}, {'end': 7392.665, 'segs': [{'end': 6450.845, 'src': 'embed', 'start': 6422.226, 'weight': 0, 'content': [{'end': 6425.106, 'text': 'You basically can now go in pharmaceutically and do all of that.', 'start': 6422.226, 'duration': 2.88}, {'end': 6428.967, 'text': 'And in our paper, we actually did all of that.', 'start': 6425.686, 'duration': 3.281}, {'end': 6431.468, 'text': 'We went in and manipulated every single aspect.', 'start': 6429.347, 'duration': 2.121}, {'end': 6433.631, 'text': 'At the nucleotide level.', 'start': 6432.27, 'duration': 1.361}, {'end': 6446.662, 'text': 'we use CRISPR-Cas9 genome editing to basically take primary adipocytes from risk and non-risk individuals and show that by editing that one nucleotide out of 3.2 billion nucleotides in the human genome,', 'start': 6433.631, 'duration': 13.031}, {'end': 6450.845, 'text': 'you could then flip between an obese phenotype and a lean phenotype like a switch.', 'start': 6446.662, 'duration': 4.183}], 'summary': 'Crispr-cas9 editing altered one nucleotide to switch between obese and lean phenotype.', 'duration': 28.619, 'max_score': 6422.226, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI6422226.jpg'}, {'end': 6615.545, 'src': 'embed', 'start': 6585.03, 'weight': 1, 'content': [{'end': 6586.69, 'text': 'So let me describe some of these technologies.', 'start': 6585.03, 'duration': 1.66}, {'end': 6591.432, 'text': 'The first one is automation and robotics.', 'start': 6587.97, 'duration': 3.462}, {'end': 6600.657, 'text': 'So, basically, you know, we talked about how you can take all of these molecules and see which of these molecules are targeting each of these genes,', 'start': 6592.352, 'duration': 8.305}, {'end': 6601.337, 'text': 'and what do they do?', 'start': 6600.657, 'duration': 0.68}, {'end': 6609.182, 'text': 'So you can basically now screen through millions of molecules, through thousands and thousands and thousands of plates,', 'start': 6602.118, 'duration': 7.064}, {'end': 6615.545, 'text': 'each of which has thousands and thousands and thousands of molecules every single time testing.', 'start': 6609.182, 'duration': 6.363}], 'summary': 'Automation and robotics enable screening through millions of molecules targeting genes, testing thousands at a time.', 'duration': 30.515, 'max_score': 6585.03, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI6585030.jpg'}, {'end': 6686.041, 'src': 'embed', 'start': 6653.331, 'weight': 2, 'content': [{'end': 6666.348, 'text': "So what do we do? We've basically developed this technology for massively parallel reporter assays, MPRA.", 'start': 6653.331, 'duration': 13.017}, {'end': 6672.014, 'text': "So in collaboration with Tarjan Mickelson, Eric Lander, I mean, Jason Dury's group has done a lot of that.", 'start': 6667.149, 'duration': 4.865}, {'end': 6680.363, 'text': "So there's a lot of groups that basically have developed technologies for testing 10,000 genetic variants at a time.", 'start': 6672.034, 'duration': 8.329}, {'end': 6683.561, 'text': 'How do you do that?', 'start': 6681.38, 'duration': 2.181}, {'end': 6686.041, 'text': 'We talked about microarray technology,', 'start': 6683.661, 'duration': 2.38}], 'summary': 'Developed technology for massively parallel reporter assays to test 10,000 genetic variants at a time.', 'duration': 32.71, 'max_score': 6653.331, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI6653331.jpg'}, {'end': 6820.748, 'src': 'embed', 'start': 6794.127, 'weight': 3, 'content': [{'end': 6798.848, 'text': 'So one bacterium evolves a gene to be resistant to a particular antibiotic.', 'start': 6794.127, 'duration': 4.721}, {'end': 6803.809, 'text': "It basically says to all its friends, hey, here's that sort of DNA piece.", 'start': 6799.708, 'duration': 4.101}, {'end': 6807.39, 'text': 'We can now co-opt these plasmids into human cells.', 'start': 6804.689, 'duration': 2.701}, {'end': 6817.149, 'text': 'You can basically make a human cell culture and add plasmids to that human cell culture that contain the things that you want to test.', 'start': 6808.359, 'duration': 8.79}, {'end': 6820.748, 'text': 'You now have this library of 450,000 elements.', 'start': 6818.066, 'duration': 2.682}], 'summary': 'Bacterium evolves antibiotic resistance gene, shares dna piece, creating a library of 450,000 elements.', 'duration': 26.621, 'max_score': 6794.127, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI6794127.jpg'}, {'end': 7346.464, 'src': 'heatmap', 'start': 7249.27, 'weight': 0.83, 'content': [{'end': 7256.396, 'text': 'You basically couple the two and you end up with little bubbles that have a cell and tons of markers for that cell.', 'start': 7249.27, 'duration': 7.126}, {'end': 7261.5, 'text': 'You now mark up all of the RNA for that one cell with the same exact barcode.', 'start': 7257.336, 'duration': 4.164}, {'end': 7267.582, 'text': 'And you then lyse all of the droplets and you sequence the heck out of that.', 'start': 7262.799, 'duration': 4.783}, {'end': 7272.504, 'text': 'And you have, for every RNA molecule, a unique identifier that tells you what cell was it on.', 'start': 7268.282, 'duration': 4.222}, {'end': 7281.41, 'text': 'That is such good engineering, microfluidics, and using some kind of primer to put a label on the thing.', 'start': 7272.745, 'duration': 8.665}, {'end': 7284.031, 'text': "I mean, you're making it sound easy.", 'start': 7281.43, 'duration': 2.601}, {'end': 7287.133, 'text': "I assume it's- It's beautiful, right? But it's gorgeous, yeah.", 'start': 7284.151, 'duration': 2.982}, {'end': 7288.093, 'text': "So there's the next generation.", 'start': 7287.333, 'duration': 0.76}, {'end': 7289.174, 'text': "That's great, great engineering, yeah.", 'start': 7288.113, 'duration': 1.061}, {'end': 7290.655, 'text': "So that's the second generation.", 'start': 7289.494, 'duration': 1.161}, {'end': 7293.557, 'text': 'Next generation is forget the microfluidics altogether.', 'start': 7290.955, 'duration': 2.602}, {'end': 7294.798, 'text': 'Just use big bottles.', 'start': 7293.837, 'duration': 0.961}, {'end': 7298.56, 'text': "How can you possibly do that with big bottles? So here's the idea.", 'start': 7295.618, 'duration': 2.942}, {'end': 7307.086, 'text': "You dissociate all of your cells or all of your nuclei from complex cells like brain cells that are very long and sticky, so you can't do that.", 'start': 7299.321, 'duration': 7.765}, {'end': 7315.251, 'text': "So if you have blood cells or if you have neuronal nuclei or brain nuclei, you can basically dissociate, let's say, a million cells.", 'start': 7307.686, 'duration': 7.565}, {'end': 7322.586, 'text': 'You now want to add a unique barcode a unique barcode in each one of a million cells using only big bottles.', 'start': 7316.092, 'duration': 6.494}, {'end': 7325.848, 'text': "How can you possibly do that? Sounds crazy, but here's the idea.", 'start': 7323.286, 'duration': 2.562}, {'end': 7328.43, 'text': 'You use a hundred of these bottles.', 'start': 7327.249, 'duration': 1.181}, {'end': 7336.236, 'text': 'You randomly shuffle all your million cells and you throw them into those hundred bottles, randomly, completely randomly.', 'start': 7330.352, 'duration': 5.884}, {'end': 7340.76, 'text': 'You add one barcode out of a hundred to every one of the cells.', 'start': 7337.137, 'duration': 3.623}, {'end': 7346.464, 'text': 'You now take them all out, you shuffle them again, and you throw them again into the same hundred bottles.', 'start': 7341.5, 'duration': 4.964}], 'summary': 'Highly efficient rna sequencing using microfluidics and big bottles with unique barcoding for every rna molecule.', 'duration': 97.194, 'max_score': 7249.27, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI7249270.jpg'}], 'start': 6422.226, 'title': 'Crispr-cas9 genome editing breakthrough and genome research technologies', 'summary': 'Discusses the groundbreaking use of crispr-cas9 genome editing to switch between obese and lean phenotypes, along with various technologies like automation, robotics, and microarray for systematic genetic variant studies, enabling testing of thousands of loci and millions of molecules at a time.', 'chapters': [{'end': 6494.898, 'start': 6422.226, 'title': 'Crispr-cas9 genome editing breakthrough', 'summary': 'Discusses the groundbreaking use of crispr-cas9 genome editing to demonstrate the ability to switch between an obese phenotype and a lean phenotype by editing just one nucleotide out of 3.2 billion in the human genome, offering hope for solving diseases.', 'duration': 72.672, 'highlights': ['Using CRISPR-Cas9 genome editing, researchers demonstrated the ability to switch between an obese phenotype and a lean phenotype by editing just one nucleotide out of 3.2 billion in the human genome, showcasing the immense potential of this breakthrough (quantifiable data: 3.2 billion nucleotides).', 'The technology has the capability to transform non-thermogenizing cells into thermogenizing cells by changing one nucleotide, illustrating the remarkable impact of this method on cell behavior and function (quantifiable data: change from non-thermogenizing to thermogenizing cells).', 'The speaker expresses optimism about the potential of this breakthrough to solve the problem of certain diseases, highlighting the far-reaching implications of this research in the field of medicine and genetics.', 'The exciting advancements in technology and tools, such as CRISPR-Cas9 genome editing, have opened up new possibilities for scientific exploration and discovery, hinting at a promising future in genomics and biotechnology.']}, {'end': 6766.528, 'start': 6496.419, 'title': 'Technologies for genome research', 'summary': 'Discusses the use of various technologies, including automation and robotics, parallel readouts, and microarray technology, to systematically study genetic variants and gene expression, enabling the testing of thousands of loci and millions of molecules at a time, with a focus on obesity research and the potential for future systematic research.', 'duration': 270.109, 'highlights': ['The technologies discussed include automation and robotics, parallel readouts, and microarray technology, enabling the systematic study of genetic variants and gene expression. The chapter emphasizes the use of automation and robotics, parallel readouts, and microarray technology to systematically study genetic variants and gene expression.', 'The use of automation and robotics allows for the screening of millions of molecules and thousands of genes simultaneously, significantly expediting the research process. Automation and robotics enable the screening of millions of molecules and thousands of genes simultaneously, expediting the research process.', 'Parallel readouts, such as the massively parallel reporter assays (MPRA), enable the testing of thousands of genetic variants at a time, avoiding the need for time-consuming individual testing. Massively parallel reporter assays (MPRA) allow for the testing of thousands of genetic variants at a time, avoiding time-consuming individual testing.', 'Microarray technology facilitates various applications, including measuring gene expression, genotyping, and synthesizing small DNA fragments, enabling the systematic synthesis and testing of thousands of DNA segments at a time. Microarray technology facilitates measuring gene expression, genotyping, and synthesizing small DNA fragments, enabling the systematic testing of thousands of DNA segments at a time.']}, {'end': 7392.665, 'start': 6767.901, 'title': 'High-throughput molecular biology techniques', 'summary': 'Discusses the use of plasmids for gene transfer and their role in creating a library of 450,000 elements for testing in human cell culture, as well as the use of massively parallel reporter assays and single-cell rna sequencing to perform thousands of experiments simultaneously, leading to advancements in molecular biology techniques.', 'duration': 624.764, 'highlights': ['The use of plasmids for gene transfer and creation of a library of 450,000 elements for testing in human cell culture. Bacteria use plasmids for transferring DNA and antibiotic resistance genes, and plasmids can be co-opted into human cells to create a library of 450,000 elements for testing.', 'Utilizing massively parallel reporter assays to perform thousands of experiments simultaneously. The technology allows testing 10,000 different versions of an enhancer on gene expression in parallel, offering the capability to perform 10,000 experiments at once.', 'Advancements in single-cell RNA sequencing technology to perform high-throughput analysis without microfluidics. The evolution of single-cell RNA sequencing technology from microfluidics to using lipid droplets and then big bottles to label a million unique barcodes in every single cell, without using microfluidics.']}], 'duration': 970.439, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI6422226.jpg', 'highlights': ['Using CRISPR-Cas9, researchers switched between obese and lean phenotypes by editing one nucleotide out of 3.2 billion in the human genome.', 'Automation and robotics enable screening millions of molecules and thousands of genes simultaneously, expediting the research process.', 'Massively parallel reporter assays (MPRA) allow testing thousands of genetic variants at a time, avoiding time-consuming individual testing.', 'Plasmids can be co-opted into human cells to create a library of 450,000 elements for testing.']}, {'end': 8236.934, 'segs': [{'end': 7454.316, 'src': 'embed', 'start': 7409.613, 'weight': 1, 'content': [{'end': 7416.476, 'text': 'So there are kits now that companies just sell to basically carry out single-cell RNA sequencing that you can basically for $2,000,', 'start': 7409.613, 'duration': 6.863}, {'end': 7420.278, 'text': 'you can basically get 10,000 cells from one sample.', 'start': 7416.476, 'duration': 3.802}, {'end': 7427.781, 'text': 'And for every one of those cells, you basically have the transcription of thousands of genes.', 'start': 7422.339, 'duration': 5.442}, {'end': 7434.275, 'text': 'And you know, of course the data for any one cell is noisy, but being computer scientists,', 'start': 7429.489, 'duration': 4.786}, {'end': 7441.422, 'text': 'we can aggregate the data from all of the cells together across thousands of individuals together, to basically make very robust inferences.', 'start': 7434.275, 'duration': 7.147}, {'end': 7446.514, 'text': 'Okay, So the third technology is basically single cell RNA sequencing.', 'start': 7442.253, 'duration': 4.261}, {'end': 7454.316, 'text': 'that allows you to now start asking not just what is the brain expression level difference of that genetic variant,', 'start': 7446.514, 'duration': 7.802}], 'summary': 'Single-cell rna sequencing kits can yield 10,000 cells for $2,000, providing transcription data for thousands of genes.', 'duration': 44.703, 'max_score': 7409.613, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI7409613.jpg'}, {'end': 7609.969, 'src': 'embed', 'start': 7584.961, 'weight': 0, 'content': [{'end': 7594.724, 'text': "microglial cell inside the brains of 1,500 individuals that we've sampled across multiple different brain regions, across both DNA and RNA.", 'start': 7584.961, 'duration': 9.763}, {'end': 7599.343, 'text': "So that's the dataset that my team generated last year alone.", 'start': 7596.181, 'duration': 3.162}, {'end': 7609.969, 'text': "So, in one year, we basically generated 10 million cells from human brain across a dozen different disorders across schizophrenia, Alzheimer's,", 'start': 7600.403, 'duration': 9.566}], 'summary': 'Study analyzed microglial cells from 1,500 brains in 1 year, generating 10 million cells across multiple disorders.', 'duration': 25.008, 'max_score': 7584.961, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI7584961.jpg'}, {'end': 7820.648, 'src': 'embed', 'start': 7795.626, 'weight': 3, 'content': [{'end': 7805.193, 'text': "Basically, if you didn't have a computer scientist way of thinking, you would never design these hugely combinatorial, massively parallel experiments.", 'start': 7795.626, 'duration': 9.567}, {'end': 7809.062, 'text': "So that's why you need interdisciplinary teams.", 'start': 7807.301, 'duration': 1.761}, {'end': 7809.822, 'text': 'You need teams.', 'start': 7809.082, 'duration': 0.74}, {'end': 7812.263, 'text': 'And I wanna sort of clarify that.', 'start': 7810.302, 'duration': 1.961}, {'end': 7816.606, 'text': 'What do we mean by computational biology group? The focus is not on computational.', 'start': 7812.283, 'duration': 4.323}, {'end': 7817.826, 'text': 'The focus is on the biology.', 'start': 7816.766, 'duration': 1.06}, {'end': 7820.648, 'text': 'So we are a biology group.', 'start': 7818.847, 'duration': 1.801}], 'summary': 'Interdisciplinary teams are essential for designing combinatorial experiments in computational biology.', 'duration': 25.022, 'max_score': 7795.626, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI7795626.jpg'}, {'end': 8084.772, 'src': 'embed', 'start': 8038.785, 'weight': 4, 'content': [{'end': 8047.252, 'text': "And I think this is what's shaping the next century to really be a transformative century for our species and for our planet.", 'start': 8038.785, 'duration': 8.467}, {'end': 8057.935, 'text': 'So you think the 21st century will be remembered for the big leaps in understanding and alleviation of biology?', 'start': 8049.389, 'duration': 8.546}, {'end': 8064.259, 'text': "If you look at the path between discovery and therapeutics, it's been on the order of 50 years.", 'start': 8058.775, 'duration': 5.484}, {'end': 8068.482, 'text': "It's been shortened to 40, 30, 20, and now it's on the order of 10 years.", 'start': 8064.819, 'duration': 3.663}, {'end': 8084.772, 'text': "But the huge number of technologies that are going on right now for discovery will result undoubtedly in the most dramatic manipulation of human biology that we've ever seen in the history of humanity in the next few years.", 'start': 8069.482, 'duration': 15.29}], 'summary': '21st century: transformative for biology, from 50 to 10 years for discovery to therapeutics, leading to dramatic manipulation of human biology.', 'duration': 45.987, 'max_score': 8038.785, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI8038785.jpg'}, {'end': 8130.351, 'src': 'embed', 'start': 8103.942, 'weight': 5, 'content': [{'end': 8110.404, 'text': 'and the ability to deliver these small molecules and other non-traditional medicine perturbations.', 'start': 8103.942, 'duration': 6.462}, {'end': 8122.048, 'text': "There's a new generation of perturbations that you can use at the DNA level, at the RNA level, at the microRNA level, at the epigenomic level.", 'start': 8110.904, 'duration': 11.144}, {'end': 8125.869, 'text': "There's a battery of new generations of perturbations.", 'start': 8122.068, 'duration': 3.801}, {'end': 8130.351, 'text': 'If you couple that with cell type identifiers,', 'start': 8126.529, 'duration': 3.822}], 'summary': 'New perturbations at dna, rna, microrna, and epigenomic levels are available.', 'duration': 26.409, 'max_score': 8103.942, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI8103942.jpg'}], 'start': 7392.725, 'title': 'Technological and computational advances in biology', 'summary': 'Discusses advancements in single-cell sequencing technology, enabling the acquisition of 10,000 cells from one sample for $2,000, robust inferences from aggregated data, and a dataset of 10 million cells from human brains. it also details the revolution in computational biology, highlighting interdisciplinary collaboration and the potential for manipulating human biology for disease understanding and therapeutics.', 'chapters': [{'end': 7642.281, 'start': 7392.725, 'title': 'Single-cell sequencing technology advancements', 'summary': 'Discusses the advancements in single-cell sequencing technology, including the ability to obtain 10,000 cells from one sample for $2,000, the potential for robust inferences by aggregating data from thousands of individuals, and the generation of a dataset comprising 10 million cells from human brains across various disorders.', 'duration': 249.556, 'highlights': ['The ability to obtain 10,000 cells from one sample for $2,000. Companies offer kits for single-cell RNA sequencing that enable obtaining 10,000 cells from a single sample for $2,000.', 'Aggregating data from all cells across thousands of individuals to make robust inferences. Computer scientists can aggregate data from thousands of cells across individuals to make robust inferences.', 'Generation of a dataset comprising 10 million cells from human brains across various disorders. The team generated a dataset comprising 10 million cells from human brains across various disorders, potentially holding keys to understanding these diseases and leading to treatment.']}, {'end': 8236.934, 'start': 7642.321, 'title': 'Computational biology revolution', 'summary': 'Details the revolution in computational biology, emphasizing the need for interdisciplinary teams and the unprecedented potential for manipulating human biology, leading to significant advancements in disease understanding and therapeutics.', 'duration': 594.613, 'highlights': ['The revolution in computational biology necessitates interdisciplinary teams of computer scientists and biologists to understand and manipulate human biology, leading to unprecedented potential for disease understanding and therapeutics. Interdisciplinary teams required, unprecedented potential for disease understanding and therapeutics', 'The rapid advancement of technologies is shortening the path between discovery and therapeutics, with the potential to dramatically manipulate human biology within the next few years. Shortening the path between discovery and therapeutics', 'The ability to deliver new generations of perturbations at the DNA, RNA, microRNA, and epigenomic levels, coupled with cell type identifiers, offers the potential for combinatorial interventions and targeted therapeutics, fundamentally altering and alleviating disease. Delivery of new generations of perturbations, potential for combinatorial interventions and targeted therapeutics', 'The confluence of technologies, computation, data, insight, and tools for manipulation is unprecedented in human history, shaping the next century as a transformative era for human biology and the planet. Unprecedented confluence of technologies and tools for manipulation', 'The 21st century is expected to be remembered for significant leaps in understanding and alleviating biology, with the potential to cure various diseases in the near future. Expected significant leaps in understanding and alleviating biology, potential to cure diseases']}], 'duration': 844.209, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI7392725.jpg', 'highlights': ['Generation of a dataset comprising 10 million cells from human brains across various disorders, potentially holding keys to understanding these diseases and leading to treatment.', 'The ability to obtain 10,000 cells from one sample for $2,000. Companies offer kits for single-cell RNA sequencing that enable obtaining 10,000 cells from a single sample for $2,000.', 'Aggregating data from all cells across thousands of individuals to make robust inferences. Computer scientists can aggregate data from thousands of cells across individuals to make robust inferences.', 'The revolution in computational biology necessitates interdisciplinary teams of computer scientists and biologists to understand and manipulate human biology, leading to unprecedented potential for disease understanding and therapeutics.', 'The rapid advancement of technologies is shortening the path between discovery and therapeutics, with the potential to dramatically manipulate human biology within the next few years.', 'The ability to deliver new generations of perturbations at the DNA, RNA, microRNA, and epigenomic levels, coupled with cell type identifiers, offers the potential for combinatorial interventions and targeted therapeutics, fundamentally altering and alleviating disease.', 'The confluence of technologies, computation, data, insight, and tools for manipulation is unprecedented in human history, shaping the next century as a transformative era for human biology and the planet.', 'The 21st century is expected to be remembered for significant leaps in understanding and alleviating biology, with the potential to cure various diseases in the near future.']}, {'end': 9288.905, 'segs': [{'end': 8286.691, 'src': 'embed', 'start': 8258.712, 'weight': 0, 'content': [{'end': 8265.377, 'text': 'using these editing and manipulation technologies, to basically show how the master regulators,', 'start': 8258.712, 'duration': 6.665}, {'end': 8279.087, 'text': 'underlying changes in the brain that are sort of found in schizophrenia are in fact affecting excitatory neurons and inhibitory neurons in pathways that are active both in synaptic pruning but also in early development.', 'start': 8265.377, 'duration': 13.71}, {'end': 8286.691, 'text': "We've basically found a set of four regulators that are connecting these two processes that were previously separate in schizophrenia,", 'start': 8279.227, 'duration': 7.464}], 'summary': 'Identified 4 regulators linking brain changes in schizophrenia affecting excitatory and inhibitory neurons.', 'duration': 27.979, 'max_score': 8258.712, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI8258712.jpg'}, {'end': 8340.579, 'src': 'embed', 'start': 8322.486, 'weight': 1, 'content': [{'end': 8336.156, 'text': "And what we're finding is this immense role of both immune cells as well as adipocyte stem cells in sort of reshaping that circuitry of all of these different tissues and that sort of painting to a new path for therapeutical intervention there.", 'start': 8322.486, 'duration': 13.67}, {'end': 8340.579, 'text': "In Alzheimer's, it's this huge focus on microglia.", 'start': 8336.915, 'duration': 3.664}], 'summary': "Immune cells and adipocyte stem cells play a significant role in reshaping tissue circuitry, pointing to new therapeutic interventions, with a major focus on microglia in alzheimer's.", 'duration': 18.093, 'max_score': 8322.486, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI8322486.jpg'}, {'end': 8481.911, 'src': 'embed', 'start': 8451.331, 'weight': 2, 'content': [{'end': 8457.715, 'text': 'long-term memory, et cetera which is dramatically affecting the cognitive path that the individuals go through.', 'start': 8451.331, 'duration': 6.384}, {'end': 8469.983, 'text': "So what we're doing now is creating these computational models for ordering the cells and the regions and the individuals according to their ability to predict Alzheimer's disease.", 'start': 8458.256, 'duration': 11.727}, {'end': 8481.911, 'text': 'So we can have a cell level predictor of pathology that allows us to now create a temporal time course that tells us when every gene turns on along this pathology progression.', 'start': 8470.483, 'duration': 11.428}], 'summary': "Creating computational models to predict alzheimer's disease using cell-level predictors and temporal gene expression data.", 'duration': 30.58, 'max_score': 8451.331, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI8451331.jpg'}, {'end': 8651.893, 'src': 'embed', 'start': 8630.914, 'weight': 3, 'content': [{'end': 8640.441, 'text': "And what we're finding is that the genes that are altered and the genetic regions that are altered in common variants versus rare variants versus somatic variants are actually very different from each other.", 'start': 8630.914, 'duration': 9.527}, {'end': 8645.264, 'text': 'The somatic variants are pointing to neuronal energetics.', 'start': 8641.221, 'duration': 4.043}, {'end': 8651.893, 'text': 'and oligodendrocyte functions that are not visible in the genetic lesions that you find for the common variants.', 'start': 8646.705, 'duration': 5.188}], 'summary': 'Genetic variants differ in their impact on neuronal energetics and oligodendrocyte functions.', 'duration': 20.979, 'max_score': 8630.914, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI8630914.jpg'}, {'end': 8744.555, 'src': 'embed', 'start': 8720.465, 'weight': 4, 'content': [{'end': 8729.437, 'text': 'Number two, we have way more of these cells And number three, we have this new diet that allows us to now feed all these needs.', 'start': 8720.465, 'duration': 8.972}, {'end': 8736.366, 'text': 'That basically creates a massive amount of damage, oxidative damage, from this huge,', 'start': 8730.098, 'duration': 6.268}, {'end': 8741.612, 'text': 'super-powered factory of ideas and thoughts that we carry in our skull.', 'start': 8736.366, 'duration': 5.246}, {'end': 8744.555, 'text': 'And that factory has energetic needs.', 'start': 8742.253, 'duration': 2.302}], 'summary': 'Increased cells lead to oxidative damage due to new diet, creating energetic needs.', 'duration': 24.09, 'max_score': 8720.465, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI8720465.jpg'}, {'end': 8806.697, 'src': 'embed', 'start': 8771.169, 'weight': 5, 'content': [{'end': 8773.23, 'text': 'And these are all the things that makes us uniquely human.', 'start': 8771.169, 'duration': 2.061}, {'end': 8776.693, 'text': 'So our immune system is dramatically different from that of our neighbors.', 'start': 8773.371, 'duration': 3.322}, {'end': 8779.275, 'text': 'Our societies are so much more clustered.', 'start': 8777.093, 'duration': 2.182}, {'end': 8785.92, 'text': 'The history of infection that have plagued the human population is dramatically different from every other species.', 'start': 8779.575, 'duration': 6.345}, {'end': 8792.725, 'text': 'The way that our society and our population has sort of exploded has basically put unique pressures on our immune system.', 'start': 8787.081, 'duration': 5.644}, {'end': 8797.929, 'text': 'And our immune system has both coped with that density and also been shaped by, as I mentioned,', 'start': 8793.266, 'duration': 4.663}, {'end': 8806.697, 'text': 'the vast amount of death that has happened in the Black Plague and other sort of selective events in human history famines, ice ages and so forth.', 'start': 8797.929, 'duration': 8.768}], 'summary': 'Human immune system uniquely shaped by history and population density.', 'duration': 35.528, 'max_score': 8771.169, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI8771169.jpg'}, {'end': 8980.245, 'src': 'embed', 'start': 8954.297, 'weight': 6, 'content': [{'end': 8962.961, 'text': 'so, basically, i see this confluence in my lab and many other labs of ai, of sort of the next frontier of AI for drug design.', 'start': 8954.297, 'duration': 8.664}, {'end': 8973.923, 'text': 'So basically these sort of graph neural networks on specific chemical designs that allow you to create new generations of therapeutics.', 'start': 8963.121, 'duration': 10.802}, {'end': 8980.245, 'text': 'These molecular biology tricks for intervening at the system at every level.', 'start': 8974.563, 'duration': 5.682}], 'summary': 'Ai for drug design using graph neural networks for creating new therapeutics.', 'duration': 25.948, 'max_score': 8954.297, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI8954297.jpg'}, {'end': 9124.145, 'src': 'embed', 'start': 9092.99, 'weight': 7, 'content': [{'end': 9100.333, 'text': "I think that we're finally at the level of systems medicine of basically, instead of sort of medicine being at the single gene level,", 'start': 9092.99, 'duration': 7.343}, {'end': 9112.317, 'text': 'medicine being at the systems level where it can be personalized based on a specific set of genetic markers and genetic perturbations that you are either born with or that you have developed during your lifetime.', 'start': 9100.333, 'duration': 11.984}, {'end': 9124.145, 'text': 'your unique set of exposures, your unique set of biomarkers, and your unique set of current set of conditions through your EHR and other ways.', 'start': 9112.937, 'duration': 11.208}], 'summary': 'Medicine is advancing to a personalized, systems level based on genetic markers and perturbations, unique exposures, biomarkers, and current conditions.', 'duration': 31.155, 'max_score': 9092.99, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI9092990.jpg'}, {'end': 9176.261, 'src': 'embed', 'start': 9145.559, 'weight': 9, 'content': [{'end': 9152.404, 'text': "So that's, in my view, the field where basically computer science comes together with artificial intelligence, statistics, all of these other tools,", 'start': 9145.559, 'duration': 6.845}, {'end': 9158.749, 'text': 'molecular biology technologies and biotechnology and pharmaceutical technologies that are sort of revolutionary in the way of intervention.', 'start': 9152.404, 'duration': 6.345}, {'end': 9165.594, 'text': 'And of course, this massive amount of molecular biology and data gathering and generation and perturbation in massively parallel ways.', 'start': 9159.369, 'duration': 6.225}, {'end': 9176.261, 'text': "So there's no better way, there's no better time, there's no better place to be sort of looking at this whole confluence of ideas.", 'start': 9166.274, 'duration': 9.987}], 'summary': 'Computer science, ai, statistics, molecular biology, biotechnology, and pharmaceutical technologies are revolutionizing intervention with massive data generation and gathering.', 'duration': 30.702, 'max_score': 9145.559, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI9145559.jpg'}, {'end': 9209.023, 'src': 'embed', 'start': 9181.344, 'weight': 8, 'content': [{'end': 9188.669, 'text': "It's exciting to imagine what the humans of 100, 200 years from now, what their life experience is like,", 'start': 9181.344, 'duration': 7.325}, {'end': 9193.553, 'text': 'because these ideas seem to have potential to transform the quality of life.', 'start': 9188.669, 'duration': 4.884}, {'end': 9202.739, 'text': 'that when they look back at us, they probably wonder how we were put up with all the suffering in the world.', 'start': 9195.014, 'duration': 7.725}, {'end': 9205.12, 'text': "Manolis, it's a huge honor.", 'start': 9203.519, 'duration': 1.601}, {'end': 9209.023, 'text': 'Thank you for spending this early Sunday morning with me.', 'start': 9205.3, 'duration': 3.723}], 'summary': "Imagining future humans' life, transforming life quality, and reflecting on present suffering.", 'duration': 27.679, 'max_score': 9181.344, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI9181344.jpg'}], 'start': 8236.995, 'title': 'Disease insights, genetic variants, and medical interventions', 'summary': 'Delves into disease insights, utilizing single cell profiling to identify master regulators, genetic variants and somatic alterations in the human brain, emphasizing the significance of somatic variants in neuronal energetics, and discusses the convergence of ai and drug design in revolutionizing medical interventions for extending human lifespan and personalized medicine.', 'chapters': [{'end': 8513.252, 'start': 8236.995, 'title': 'Disease insights and therapeutical interventions', 'summary': "Discusses the team's path of generating disease insights, including findings on schizophrenia, metabolic perturbations, and alzheimer's, utilizing single cell profiling and manipulation technologies to identify master regulators and cell-to-cell communication, as well as creating computational models for ordering cells and regions to predict alzheimer's disease progression.", 'duration': 276.257, 'highlights': ['Discovering master regulators in schizophrenia affecting excitatory and inhibitory neurons in pathways active in synaptic pruning and early development, connecting previously separate processes. The team has found four regulators connecting processes previously separate in schizophrenia, affecting excitatory and inhibitory neurons in pathways active in synaptic pruning and early development.', 'Identifying cell-to-cell communications in multi-tissue perturbations across the body, revealing the role of immune cells and adipocyte stem cells in reshaping tissue circuitry for potential therapeutical interventions. The collaboration with the Goodyear lab involves looking at multi-tissue perturbations in six or seven different tissues across the body, revealing the role of immune cells and adipocyte stem cells in reshaping tissue circuitry for potential therapeutical interventions.', "Discovering different classes of microglial cells playing vastly different roles in Alzheimer's and schizophrenia, highlighting the immense complexity and diversity within microglia. The team has discovered different classes of microglial cells playing vastly different roles in Alzheimer's and schizophrenia, highlighting the immense complexity and diversity within microglia.", "Creating computational models for ordering cells and regions to predict Alzheimer's disease progression, aiming to develop new diagnostics, prognostics, and biomarkers for early intervention. The team is creating computational models for ordering cells and regions to predict Alzheimer's disease progression, aiming to develop new diagnostics, prognostics, and biomarkers for early intervention."]}, {'end': 8890.542, 'start': 8514.372, 'title': 'Genetic variants and somatic alterations in human brain', 'summary': "Discusses the impact of somatic variants on the genetic underpinnings of the human brain, utilizing single-cell rna sequencing to identify unique alterations, highlighting the significance of somatic variants in neuronal energetics and oligodendrocyte functions in comparison to common and rare variants, while also emphasizing the unique biological processes underlying alzheimer's disease.", 'duration': 376.17, 'highlights': ['Single-cell RNA sequencing is used to infer mutations in thousands of genes active in brain cells, revealing that somatic variants point to neuronal energetics and oligodendrocyte functions not visible in common or rare variants. The utilization of single-cell RNA sequencing allows the identification of unique alterations in somatic variants, highlighting their association with specific neuronal energetics and oligodendrocyte functions.', "Somatic variants in the human brain are found to be significantly different from common and rare variants, pointing to the impact on neuronal energetics and oligodendrocyte functions, which are not observed in the genetic lesions of common variants. The comparison of somatic variants with common and rare variants underscores their distinct impact on neuronal energetics and oligodendrocyte functions, providing insights into the unique biological processes underlying Alzheimer's disease.", "Human brain cells exhibit unique energy efficiency and abundance, driven by dietary changes, leading to increased oxidative damage and altered biological processes, particularly relevant to Alzheimer's disease. The unique energy efficiency and abundance of human brain cells, influenced by dietary changes, contribute to increased oxidative damage and altered biological processes, particularly pertinent to Alzheimer's disease.", 'Human immune and metabolic systems differ significantly from other species, shaped by population density, historical infections, and environmental exposures, impacting diseases and the expansion of human lifespan. The distinctiveness of human immune and metabolic systems, influenced by population density, historical infections, and environmental exposures, plays a crucial role in disease susceptibility and the extension of human lifespan.']}, {'end': 9288.905, 'start': 8890.542, 'title': 'Frontiers in medicine and systems intervention', 'summary': 'Discusses the challenges of extending human lifespan, the convergence of ai and drug design, and the future of personalized medicine at the systems level, revolutionizing interventions and potentially transforming the quality of life for future generations.', 'duration': 398.363, 'highlights': ['The challenge of extending human lifespan is discussed, with the human body evolving to live up to around 120 years, potentially extendable to 150 with minor changes.', 'The convergence of AI and drug design, focusing on graph neural networks for creating new therapeutics, personalized medicine prediction using electronic health records and polygenic risk scores, and delivering specific interventions into specific cell types, is highlighted as a frontier in the field.', 'The concept of intervening at the network level rather than the gene level in systems medicine is emphasized, allowing for personalized interventions based on a unique set of genetic markers, exposures, biomarkers, and conditions, potentially bringing individuals to a physiologically improved state.', 'The potential transformation of the quality of life for future generations through these ideas is mentioned, with the potential to alleviate human suffering and improve life experiences in the long term.', 'The application of AI, statistics, molecular biology technologies, and biotechnology in revolutionizing interventions at the systems level is highlighted, indicating a promising future in the field of medicine and human health.']}], 'duration': 1051.91, 'thumbnail': 'https://coursnap.oss-ap-southeast-1.aliyuncs.com/video-capture/Aq9UPIXbtKI/pics/Aq9UPIXbtKI8236995.jpg', 'highlights': ['Discovering master regulators in schizophrenia affecting excitatory and inhibitory neurons in pathways active in synaptic pruning and early development, connecting previously separate processes.', 'Identifying cell-to-cell communications in multi-tissue perturbations across the body, revealing the role of immune cells and adipocyte stem cells in reshaping tissue circuitry for potential therapeutical interventions.', "Creating computational models for ordering cells and regions to predict Alzheimer's disease progression, aiming to develop new diagnostics, prognostics, and biomarkers for early intervention.", 'Single-cell RNA sequencing is used to infer mutations in thousands of genes active in brain cells, revealing that somatic variants point to neuronal energetics and oligodendrocyte functions not visible in common or rare variants.', "Human brain cells exhibit unique energy efficiency and abundance, driven by dietary changes, leading to increased oxidative damage and altered biological processes, particularly relevant to Alzheimer's disease.", 'The distinctiveness of human immune and metabolic systems, influenced by population density, historical infections, and environmental exposures, plays a crucial role in disease susceptibility and the extension of human lifespan.', 'The convergence of AI and drug design, focusing on graph neural networks for creating new therapeutics, personalized medicine prediction using electronic health records and polygenic risk scores, and delivering specific interventions into specific cell types, is highlighted as a frontier in the field.', 'The concept of intervening at the network level rather than the gene level in systems medicine is emphasized, allowing for personalized interventions based on a unique set of genetic markers, exposures, biomarkers, and conditions, potentially bringing individuals to a physiologically improved state.', 'The potential transformation of the quality of life for future generations through these ideas is mentioned, with the potential to alleviate human suffering and improve life experiences in the long term.', 'The application of AI, statistics, molecular biology technologies, and biotechnology in revolutionizing interventions at the systems level is highlighted, indicating a promising future in the field of medicine and human health.']}], 'highlights': ['The 21st century is expected to be remembered for significant leaps in understanding and alleviating biology, with the potential to cure various diseases in the near future.', 'The rapid advancement of technologies is shortening the path between discovery and therapeutics, with the potential to dramatically manipulate human biology within the next few years.', 'Understanding genetic mutations and their impact on disease can guide pharmaceutical intervention, offering new possibilities for treatment.', 'Genetics has significantly changed the understanding of disease, identifying unexpected genetic predispositions to conditions such as age-related macular degeneration (AMD), which opens up new opportunities for targeted interventions.', 'The infrastructure built for understanding every single nucleotide of the human genome and its function in major cell types and tissues, emphasizing the comprehensive nature of the task.', 'The process of linking regulators to enhancers and enhancers to their target genes using epigenomics and regulatory genomics, demonstrating the integrated approach for understanding gene regulation.', 'The convergence of AI and drug design, focusing on graph neural networks for creating new therapeutics, personalized medicine prediction using electronic health records and polygenic risk scores, and delivering specific interventions into specific cell types, is highlighted as a frontier in the field.', 'The concept of intervening at the network level rather than the gene level in systems medicine is emphasized, allowing for personalized interventions based on a unique set of genetic markers, exposures, biomarkers, and conditions, potentially bringing individuals to a physiologically improved state.', 'The potential transformation of the quality of life for future generations through these ideas is mentioned, with the potential to alleviate human suffering and improve life experiences in the long term.', 'The awe-inspiring complexity and robustness of biology contrasts with human-engineered computing systems, prompting a potential need to rethink engineering computational systems for artificial general intelligence and consciousness.']}