M. Madan Babu

M. Madan Babu
MRC Laboratiry of Molecular Biology
United Kingdom

Madan Babu obtained his undergraduate degree in 2001 from the Centre for Biotechnology, Anna University, India with fellowships from the Indian Institute of Science and the Indian Academy of Sciences. He then received a LMB-Cambridge International Fellowship and a Trinity College Research Scholarship to carry out his doctoral research at the Medical Research Council's Laboratory of Molecular Biology (MRC-LMB) in Cambridge, UK. During this time, he carried out studies on the structure, evolution and dynamics of transcriptional regulatory networks by employing a combination of computational approaches. For this work, he was awarded the Max Perutz Prize for outstanding PhD research in 2004. He subsequently received an NIH International Visiting Fellowship to work at the NCBI, USA where he defined general principles of the organization of biological networks. He returned to the UK to become an independent Group Leader at the MRC Laboratory of Molecular Biology in 2006, was elected as a Schlumberger Research Fellow at Darwin College, Cambridge in 2007 and was appointed as a Programme Leader in 2010. He is a Director of Studies at Trinity College, Cambridge, an Executive Editor at Nucleic Acids Research, an Associate Editor at Molecular BioSystems and a member of the HUGO council and F1000. He has published over 100 papers, reviews and book chapters in the areas of regulatory genomics, systems biology and disordered proteins. His work has been recognized by several awards including the Biochemical Society's Early Career Award (2009), EMBO Young Investigator Award (2010), British Genetics Society's Balfour Award (2011), Royal Society of Chemistry's Molecular BioSystems Award (2011), the Biochemical Society's Colworth Medal (2013), the Protein Science Young Investigator Award (2014) from the American Protein Society and the Lister Prize from the Lister Institute of Preventive Medicine (2014).

Research interests:Regulatory Genomics and Systems Biology.
Research in my group is aimed at understanding how regulation is achieved at different scales of complexity (Molecular, Systems and Genome level) in cellular systems and how they influence genome evolution. At the molecular level, we aim to investigate regulatory proteins that are involved in protein-protein, protein-nucleic acid and protein-small molecule interactions. In particular, we aim to gain an understanding of the proteins involved in (a) GPCR receptor signalling pathway, (b) chromatin modification pathway and (c) ubiquitin pathway. At the systems level, we aim to gain an understanding of (a) how aggregation prone proteins are tolerated and regulated, (b) how pathogens could possibly exploit host machinery and signalling by secreting unstructured proteins and (c) understand the regulation and dynamics of proteins within the context of their position in the various molecular interaction networks. At the genome level, we investigate (a) the interplay between nucleosome modification and genome organization, (b) mutations and their impact on genome and transcriptome evolution, (c) the genetic basis of natural behavioural variation and (d) bacterial transcription networks and genome evolution. To pursue these lines of research, we develop new computational methods that will make use of the publicly available large-scale datasets. These include sequence, structure, expression and molecular interaction data from several different model organisms ranging from bacteria to fungi to humans. We also exploit newly available data on natural variation, cancer genome sequence and gene expression and nucleosome modification data, and information from genetic screens linking genotype with phenotype. The problems that we work on in my group have the ultimate objective of being able to identify new regulatory principles and features of regulatory systems, to exploit our findings and the general principles that we describe in specific applications such as genetic engineering, and to better understand regulatory dysfunctions leading to human diseases.

RECOMB 2015 keynote talk: The contribution of intrinsically disordered regions to protein function, cellular complexity and human diseases
In the 1960s, Christian Anfinsen postulated that the unique three-dimensional structure of a protein is determined by its amino acid sequence. This work laid the foundation for the sequence-structure-function paradigm, i.e. the sequence of a protein determines its structure, and structure determines function. However, a class of polypeptide segments called Intrinsically Disordered Regions (IDRs) defies this postulate. In this lecture, I will first describe established and emerging ideas about how disordered regions contribute to protein function. I will then discuss molecular principles of how regulatory mechanisms such as alternative splicing and asymmetric mRNA localization of transcripts encoding disordered segments can increase the functional versatility of proteins. Finally, I will discuss how disordered regions contribute to human disease and the emergence of cellular complexity during organismal evolution.