Dr. Alka Rao

Biography

Current focus of our Lab is: 1) Exploring the Making of Glycoproteins in Microbes. Glycosylation of proteins in bacteria has been categorically rejected for decades owing to the fact that the usual seat of glycosylation of proteins in eukaryote is lumen of endoplasmic reticulum (ER) and golgi body, the two structures that are absent in prokaryotes. Also as a matter of fact glycosylation was never observed before in common lab strains of microbes like E. coli, B. subtilis etc. But lately, a good number of experimental evidences have established the fact that prokaryotes indeed are able to synthesize glycoproteins and has given rise to a nascent discipline of study termed “bacterial glycoproteomics”. Infact, the glycome and its subset glycoproteome are indeed far more complex than the genome or proteome of a cell. Our lab’s primary interest is in investigating the spread, horizons and versatility of protein glycosylation in bacteria across the domain eubacteria, eventually to discern the role of bacterial glycans in the general cell biology as well as in deciphering its importance in increasingly more evident interaction between host defenses and bacterial virulence factors. 2) Studies on the Mycobacterium tuberculosis Homologs of Conserved Hypothetical Proteins forming Basic Survivasome of the Pathogen. The high throughput mutagenesis/ microarray studies and comparative genomics have led to the identification of a basic “survivasome” of M. tuberculosis genetic repertoire involved in the pathogenesis and survival of the bacterium. M. tuberculosis, an obligate pathogen with a mid size genome has a large complement approximately 35% of its total annotated protein coding ORFs found as essential. Further within these essential genes a notable fraction codes for (approximately 25%) hypothetical proteins with annotations like hypothetical/ conserved hypothetical, probable and putative etc. As long as there are multiples of conserved proteins of unknown function present with a definite and established role in survival and/or pathogenesis of the organism, the debate of a ‘complete’ understanding of the organisms as biological system will remain elusive. Therefore another interest of our lab is in identifying and studying these absolutely unexplored essential yet hypothetical, genes in order to decipher the molecular mechanisms of survival and pathogenesis of M. tuberculosis. 3) Synthesis and selection of de novo proteins/ peptide binders against essential proteins/ putative drug targets of pathogenic bacteria Another focus of our lab is to build up a base collection of potential antimicrobial binder protein/ peptides against targeted enzymes/ proteins of pathogenic bacteria like Mycobacterium tuberculosis with the help of combinatorial library generation techniques and a bacterial two hybrid system and /or phage display system. Such a collection can then provide a set of lead points for advanced research in the areas of drug designing and therapeutics against various pathogenic bacteria. Selected list of Publications and Patents: Alka Rao, Geeta Ram, Adesh Kumar Saini, Reena Vohra, Krishan Kumar, Yogendra Singh and Anand Ranganathan (2007) Synthesis and selection of de novo proteins that bind and impede cellular functions of an essential mycobacterial protein. Applied and Environmental Microbiology, 73: 1320–1331 ISSN: 0099-2240 (Print) ISSN: 1098-5336 (Online) Alka Rao, Sidharth Chopra, Geeta Ram, Ankit Gupta and Anand Ranganathan (2005) Application of the “Codon-shuffling” method. The Journal of Biological Chemistry, 280: 23605–23614 ISSN: 0021-9258 (Print) ISSN: 1083-351X (Online) Alka Rao and Anand Ranganathan (2004) Interaction studies on proteins encoded by the phthiocerol dimycocerosate locus of Mycobacterium tuberculosis. Molecular Genetics and Genomics, 272: 571-579 ISSN: 1617-4615 (print) ISSN: 1617-4623 (Online)

Research Interest

Directed evolution of Proteins/ enzymes, De novo design of combinatorial protein/ peptide libraries