CIS Colloquium Series
“Data Science approaches to GPCR signaling and implications for drug discovery”
Inviting Professor: Patrick Barth
G protein-coupled receptors (GPCRs) participate in diverse physiological processes, ranging from sensory responses such as vision, taste, and smell to those regulating behavior, the immune and the cardiac system among others. The ~800 human GPCRs sense diverse signaling molecules such as hormones and neurotransmitters to allosterically activate the associated G proteins, which in turn regulate diverse intracellular signaling pathways. In this manner, GPCRs regulate virtually every aspect of human physiology. Not surprisingly, GPCRs are the targets of over one-third of all prescribed human drugs. In this presentation, I will first discuss how one could leverage data from diverse species to infer selectivity determinants of GPCR-G protein binding, which is critical to elicit the right intracellular response. I will then discuss how one could utilize data on completely sequenced genomes of over 60,000 individuals from the human population to gain insights into natural receptor variation, which can result in variable drug response. Finally, I will present our recent work wherein by studying transcriptome data from over 30 different tissues in humans, one could begin to understand how alternative splicing creates diversity in GPCR signaling components, which may contribute to tissue-specific differences in receptor signaling. Such variations not only present challenges but also opportunities for drug development. I will conclude by discussing how understanding variation at these different dimensions, i.e., across different species, among different individuals of a species, and between tissues of a species, can provide a rich source of new hypotheses with implications for personalized medicine, drug development and understanding basic receptor biology.
M. Madan Babu is the Endowed Chair of Biological Data Science in the Department of Structural Biology at St Jude Children’s Research Hospital. He is also the Director of the Center of Excellence for Data Driven Discovery. Before joining St Jude, Madan was a Programme Leader at the MRC Laboratory of Molecular Biology in Cambridge, UK (2006-2020). Madan’s research group develops data science approaches to make biological discoveries with a particular emphasis on understanding how the precise structure and intrinsically disordered regions of proteins contribute to cellular function. His interests and publications span diverse areas in life sciences relevant to human diseases and medicine. The work from his group has been recognized with national and international awards including the Royal Society’s Francis Crick Medal, the Blavatnik Award for his work elucidating the functions of key proteins in the human genome, and the EMBO Gold Medal for his fundamental contributions to the field of computational molecular biology; specifically for his discoveries in the areas of GPCR signaling and intrinsically disordered proteins. Madan is the Chief Editor of Molecular Systems Biology and an Executive Editor of Nucleic Acids Research. He is an elected member of EMBO, Fellow of the Royal Society of Chemistry, the UK Academy of Medical Science, and the Royal Society. Madan did his post-doc from the NCBI, NIH (2006), received his Ph.D. from the MRC Lab of Molecular Biology and Trinity College, Cambridge University, UK (2004) and his undergraduate degree from the Centre for Biotechnology at Anna University in India (2001).