Structural Biology (NCCS)
1.Structural studies on proteins of M. tuberculosis
We have focused our research on M. tuberculosis for the reason that it affects most part of the poor world, and that understanding of the disease has remained inadequate despite enhanced scientific efforts. Our attempt is to determine three-dimensional structures of its proteins, and correlate the properties to the bacterial physiology and pathology, wherever possible. Our laboratory, thereofre, has been actively participating in the International Tuberculosis Structural Genomics Consortium, currently coordinated by Prof. Jim Sacchettini, Texax A& M University.
2.Structure and function studies on M. tuberculosis heat shock proteins
We have been interested in the overall properties of the M. tuberculosis Heat Shock Proteins, not that these are likely to be different than those of other well-studied prokaryotes. However, recent literature suggests that the HSPs play an important role in the pathogenesis of M. tuberculosis, and therefore our interest in this family of proteins. Our focus till now has been on the Hsp10 (GroES or Cpn10), the two Hsp60s (GroEL1/ Cpn60.1 and GroEL2/ Cpn60.2) and Hsp70 (DnaK). We have also initiated studies towards biophysical and structural characterization of the two major heat shock repressors: HspR and HrcA.
3.Structure and function studies on redox enzymes of M. tuberculosis
Redox processes play an important role in the physiology of M. tuberculosis. Since, M. tuberculosis spend substantial amount of time in the phagosomal milieu of host macrophages, it is believed that modulation of the redox reactions might help M. tuberculosis survive the hostile environment therein. We are interested in the structure and biochemical characterization of redox reactions in M.tuberculosis, with the hope that this will offer useful insights into the natural resistance of mycobacteria towards oxidative killing. Towards achieving this objective, we have undertaken studies on M. tuberculosis thioredoxins, alkylhydroperoxidases, inositol-1-phosphate synthase NrdH.
4. Large scale analysis of protein:protein interactions networks
Cellular functions are determined by intricate interactions among many components of cells. Proteins being the dominant molecules of life, interactions among all the cellular proteins direct many of the cellular responses. We have recently become interested in the analysis of genome-wide protein:protein interactions. Our interest primarily is in applying graph theory to protein:protein interactions and attempt to understand how cells respond to external environmental signals.
5.Obtaining insights into biochemical functions of proteins using 3D structural knowledge
One of the paradigms that has evolved in modern biology states that the functional properties are conferred on proteins by virtue of their overall shape and conformation. In the post-genomics era, when sequences are becoming rapidly available, the gap between the availability of sequences and understanding their functions is ever-widening. It is in this context we are attempting to analyse structures of proteins so that they can be assigned biochemical functions based on their 3D conformation.
Fields of interest
Contact infoAddress: Lab-2 (A-Bldg) National Centre for Cell Science (NCCS) Pune University Campus Ganeshkhind
Postal code: 411007
Telephone: +91 20 25708238
Fax: +91 20 25692259
- Hegde SR, Pal K, Mande SC
Differential enrichment of regulatory motifs in the composite network of protein-protein and gene regulatory interactions
BMC Syst Biol. 2014 Feb 27;8:26
- Phulera S, Mande SC
The crystal structure of Mycobacterium tuberculosis NrdH at 0.87 Å suggests a possible mode of its activity
Biochemistry. 2013 Jun 11;52(23):4056-65
- Hegde SR, Rajasingh H, Das C, Mande SS, Mande SC
Understanding communication signals during mycobacterial latency through predicted genome-wide protein interactions and boolean modeling
PLoS One. 2012;7(3):e33893
- Jailkhani N, Ravichandran S, Hegde SR, Siddiqui Z, Mande SC, Rao KV
Delineation of key regulatory elements identifies points of vulnerability in the mitogen-activated signaling network
Genome Res. 2011 Dec;21(12):2067-81
- Kumar P, Joshi DC, Akif M, Akhter Y, Hasnain SE, Mande SC
Mapping conformational transitions in cyclic AMP receptor protein: crystal structure and normal-mode analysis of Mycobacterium tuberculosis apo-cAMP receptor protein
Biophys J. 2010 Jan 20;98(2):305-14