RAJESH S. GOKHALE, Ph.D.

      Chemical Biology Group

National Institute of Immunology

           Aruna Asaf Ali Marg

             New Delhi 560 012

               rsg@nii.res.in

              +91-11-26703761

 


Rajesh S. GokhaleScientist, National Institute of Immunology

Faculty Member (Honorary), Jawaharlal Nehru Centre for Advanced Scientific Research

HHMI International Research Scholar

 

M.Sc., 1990, Indian Institute of Technology, Bombay, Mumbai

Ph.D., 1996, Indian Institute of Science, Bangalore

Postdoctoral Fellow, 1996-1999, Stanford University, USA

 

Wellcome Trust Senior Research Fellowship in Biomedical Science 2001-2006

B. M. Birla Science Prize, 2003

Swarnajayanti Fellowship, 2006-2011

 


My research group is interested to address problems related to metabolic diversity and complexity.  In this multidisciplinary program engaged at the interface of chemistry, biochemistry, and structural and molecular biology, we are elucidating the biochemical pathways leading to the assembly of various metabolites.  Our studies, in general, should identify mechanisms that facilitate generation of metabolic repertoire in nature by using limited set of genes.

 

Chemical Biology of Mycobacterium Tuberculosis

 

The microbial genome sequencing projects have revealed an unanticipated variety of metabolic and cellular capabilities.  It is therefore not surprising that microbes can successfully adapt to different habitats successfully.  M. tuberculosis has been a successful pathogen and the key to its success lies in its ability to reside and proliferate inside host macrophage despite the antimicrobial properties of these cells.  Pathogenic mycobacteria are endowed with remarkable cell envelope of fascinating molecular architecture.  Along with complex lipids and polysaccharides, mycobacterial cell envelope is associated with numerous proteins that influence cellular structure and its interactions with host cells.  Despite considerable progress in characterization of the major cellular components of M. tuberculosis, there is little information on the nature of proteins associated with the cell envelope.  Since the cell envelope constitutes the key interface between pathogen and host, the cell wall-associated proteins and lipids are presumable key determinants of pathogenesis and immunogenicity.  There is mounting evidence that despite the lack of significant genetic heterogeneity between strains of M. tuberculosis, the variable expression leading to phenotypic heterogeneity contributes towards virulence and persistence of this major killer of humankind.  We are interested in dissecting the molecular mechanisms that generate functional diversity through “enzymatic crosstalk" that will provide insight into mechanisms employed by pathogens to generate metabolite diversity.

Functional Significane of Polyketide Synthases in Dictyostelium Disscodium

 

Dictyostelium genome has revealed a very large number of genes homologous to polyketide synthases (PKSs).  Although the functional significance of these genes is not known, some of the metabolites that could be biosynthesized by PKSs have been characterized and their role in differentiation has been demonstrated.  The advances in the understanding of the biochemical basis for the programming of the polyketide biosynthesis provide an impetus and opportunity to dissect the roles of these enzymes from these versatile soil amoebae.

Dissecting Biochemical Mechanisms of the Melanocyte and Melanin Disappearnce in Vitiligo

 

The advances in neural crest cell culture and the availability of human genome sequence presents a tantalizing opportunity to carry out a multi-disciplinary study to dissect the integrated roles of different causal factors involved in the genesis of vitiligo.  Moreover, the manifestation of this disease on the skin surface provides a relatively easy access to affected cells/tissues.  In this study we are investigating into the biochemical mechanisms underlying melanin and melanocyte disappearance in vitiligo by combination of hypothesis-driven and exploratory research.

 

Significant Publications (Since 2003)

 

1.        Krithika R., Marathe U., Saxena P., Ansari M.Z., Mohanty D., Gokhale R.S. (2006) A genetic locus required for iron acquisition in Mycobacterium tuberculosis.  Proc Natl Acad Sci U S A. 103(7):2069-74.

2.        Arora P., Vats A., Saxena P., Mohanty D., Gokhale R.S. (2005) Promiscuous fatty acyl-CoA ligases produce acyl-CoA and acyl-SNAC precursors for polyketide biosynthesis. J. Am. Chem. Soc. 127(26):9388-9.

3.        Trivedi O.A., Arora P., Vats A., Ansari M.Z., Tickoo R., Sridharan V., Mohanty D., Gokhale, R.S. (2005) Dissecting the mechanism and assembly of a complex virulence mycobacterial lipid. Mol Cell 17(5):631-43.

4.        Sankarnarayanan R.*, Saxena P., Marathe U.B., Gokhale R.S.*, Shanmugam V. M., Rukmini R. (2004) A novel substrate binding tunnel in mycobacterial type III polyketide synthase reveals structural basis for generating diverse metabolites. Nat Struct Mol Biol. 11(9):894-900. (* represents corresponding authors).

5.        Trivedi O.A., Arora P., Sridharan V., Tickoo R., Mohanty D., Gokhale, R.S. (2004) Enzymic activation and transfer of fatty acids as acyl-adenylates in mycobacteria. Nature 428 (6981), 441-445.

6.        Saxena P., Yadav G., Mohanty D., Gokhale R.S. (2003): A New Family of Type III Polyketide Synthases in Mycobacterium tuberculosis. J. Biol. Chem. 278(45), 44780-44790.

Present Group Members