M. Madan Babu

2018 United Kingdom Award Winner — Faculty

Current Position:
Programme Leader

Institution:
MRC Laboratory of Molecular Biology

Discipline:
Computational Biology & Bioinformatics

Recognized for: Insights into the structural biology and molecular logic of key proteins and protein motifs, including G-protein coupled receptors and intrinsically-disordered protein regions.

Areas of Research Interest and Expertise: Computational and Systems Biology, Structural Biology, Genomics, Bioinformatics, Data Science, Personalized Medicine

Biography:

BTech, Anna University, India
PhD, MRC Laboratory of Molecular Biology, University of Cambridge, UK (Advisor: Dr. Sarah Teichmann)
Postdoctoral Scientist, NCBI, National Institutes of Health, USA (Advisor: Dr. L. Aravind)

Dr. Babu’s multi-disciplinary work employs techniques from data science, genomics, and structural biology to analyze biological systems at multiple levels. Using this innovative approach, Dr. Babu has uncovered mechanistic details of a class of proteins called G-protein-coupled receptors (GPCRs). These proteins are implicated in numerous human disorders, and drugs targeting GPCRs represent nearly 30% of all drug sales. Dr. Babu and his team identified key aspects of GPCR biology that will aid in developing more specific, targeted pharmaceuticals. Additionally, Dr. Babu has shown that many GPCRs targeted by common drugs are highly variable in the human population, so patients with different variants are likely to have different responses to the same drug. This work will begin to identify problematic treatments, and could potentially revolutionize personalized medicine. In a parallel body of work, Dr. Babu has also made fundamental discoveries in the role of unstructured proteins. About 40% of human proteins have a region where the protein becomes more flexible, less structured – these so-called intrinsically disordered regions (IDRs) have puzzled structural biologists for decades. Through a combination of genome-scale computational approaches, big-data analysis, machine learning and experimental validation, Dr. Babu and his team helped to establish the roles of IDRs in health and disease. Together, these studies shed light on key classes of proteins that are integral to human health.

“Our work focuses on extracting knowledge from large-scale datasets to uncover complex patterns, thereby making new discoveries. We analyze, integrate and mine a vast trove of biological information to derive general principles to understand how living systems work at a molecular level and how mutations cause diseases. We have obtained molecular insights into how G protein coupled receptors – a major drug target that regulates virtually every aspect of human physiology – function. We have also discovered mechanisms by which unstructured protein regions contribute to cellular function and disease. I would like to take this opportunity to thank my past and present group members, collaborators, mentors, and my family including my toddler son whose curiosity inspires me everyday. I would also like to acknowledge the MRC Laboratory of Molecular Biology for having supported my research over the years”

Key Publications:

1. J.Gsponer, M.E.Futschik, S.A.Teichmann, M.M.Babu. Tight Regulation of Unstructured Proteins: From Transcript Synthesis to Protein Degradation. Science, 2008.
2. A.J.Venkatakrishnan, X.Duepi, G.Lebon, C.G.Tate, G.F.Schertler, M.M.Babu. Molecular Signatures of G-protein-coupled receptors. Nature, 2013.
3. T.Flock, A.S.Hauser, N.Lund, D.E.Gloriam, S.Balaji, M.M.Babu. Selectivity Determinants of GPCR-G-Protein Binding. Nature, 2017.
4. A.S.Hauser, S.Chavali, I.Masuho, L.J.Jahn, K.A. Martemyanov, D.E.Gloriam, M.M.Babu. Pharmacogenomics of GPCR Drug Targets. Cell, 2018.

Other Honors:

In the Media:

Cell - Illuminating the Dark Proteome: Interview with Cell

The Royal Society - Code-cracking: using computers to understand life’s source codes

The Royal Society - Unstructured proteins: cellular complexity and human diseases

Cell Video Abstracts (YouTube) - Pharmacogenomics of GPCR drug targets