Understanding Obesity and Alzheimer’s via Epigenomics
Dec 28, 2023
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Manolis Kellis, a professor of Computer Science at MIT, discusses the cellular mechanisms of disease and interventions for maintaining health. The podcast explores genomics and epigenomics, delving into genetic associations with obesity. It also touches on challenges and triumphs of small business owners, the importance of personalized medicine, and the significance of small businesses in the economy.
Epigenomics research reveals the genetic variants and pathways related to cholesterol transport in the brain, offering potential for developing drugs to restore cognition in Alzheimer's disease.
Certain genetic variants impact the progenitor cells of white and brown fat, leading to differences in energy storage and calorie burning, contributing to obesity.
Deep dives
Exploring the Power of Genomics and Epigenomics in Understanding Human Health
Manolis Kellis, a professor of computer science at MIT, discusses the field of computational biology and how it uses large datasets to gain insights into genetics, health outcomes, and disease mechanisms. His research focuses on genomics and epigenomics, which explore the ways genes are turned on and off. Through his work on obesity and epigenomics, Kellis reveals the connection between certain genes and the development of white or brown fat in the body. He also delves into his research on Alzheimer's disease, investigating genetic variants and pathways related to cholesterol transport in the brain. Kellis emphasizes the importance of personalized medicine and developing drugs that target specific pathways to tackle complex disorders, like Alzheimer's. In the future, his goal is to continue unraveling these circuits and creating drugs that have a positive impact on human health.
Understanding the Human Genome: From Protein Coding to Control Regions
Manolis Kellis reflects on his early work on the human genome, highlighting that most of the human genome is not dedicated to protein coding. Instead, he explains that control regions within the genome dictate when and how genes express proteins. Kellis's research aims to uncover these regulatory motifs and ascertain their role in gene regulation. By exploring the language of DNA and the three-dimensional structure of control regions, he and his team strive to understand how the genome turns into a living organism. This understanding has significant implications for unveiling the basis of human variation and diseases.
Unraveling the Genetic Associations of Obesity: Beyond the FTO Gene
Manolis Kellis investigates the genetic association of obesity, focusing on the FTO gene, which was initially correlated with obesity but remained mysterious in terms of its function. Kellis's research shows that a region associated with obesity does not directly affect the FTO gene, but instead impacts two other genes that control thermogenesis and metabolic state. He identifies how certain genetic variants affect the progenitor cells of white and brown fat, leading to differences in energy storage and calorie burning. Furthermore, Kellis uncovers the distribution of the obesity-associated genetic variant in different populations, highlighting factors like positive selection and a shift in environmental conditions that contribute to obesity.
Progress in Treating Alzheimer's Disease: Understanding Genetic Variants and Pathways
Manolis Kellis explores the genetic variant ApoE4 and its link to Alzheimer's disease. By investigating problems with cholesterol transport in the brain associated with this variant, Kellis and his colleagues conduct experiments in mice that reveal the potential for restoring cognition through drugs that promote cholesterol transport. While acknowledging that clinical trials and translating findings to humans are challenging, Kellis emphasizes the importance of personalized medicine in treating Alzheimer's and other complex disorders. He envisions an approach that targets various pathways and hallmarks of the disease, developing a collection of drugs that can be tailored to an individual's specific genetic predispositions.
Manolis Kellis is a professor of Computer Science at the Massachusetts Institute of Technology. He works in computational biology, taking giant datasets relating to genetics and health outcomes and tries to understand what’s going on.
Manolis’ research focuses on genomics, and a related field called epigenomics. Manolis’ problem is this: What are the cellular mechanisms of a disease? And how can we intervene to keep people healthy?
