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Name:
Dr. Pradip Kumar Chakraborti
Expertise:
Molecular Biology and Biochemistry, Molecular Microbiology.

Contact Address:

Work

Institute of Microbial Technology,

Sector 39A, Chandigarh 160 036, India

Phone:

(+91) 172- 2690751 (direct)                                                                      

(+91) 172- 2636680, extn. 3241                                                             

Fax: (+91) 172- 2690585

Email: pradip@imtech.res.in

 

Home

House no. 1005 (Ground Floor),

Sector 39A, Chandigarh 160 036, India.

Phone: (+91) 172 2695488.

Mobile: (+91) 9815863975


Write-up of research and development interests/focus, past and present goals:

Therapeutic intervention of tuberculosis has become a complex phenomenon because of the development of drug resistant strains of the causative agent, Mycobacterium tuberculosis, and unusual life style of this bacterium within the host.  To overcome the situation, we need to have new/novel drug intervention strategies.  Therefore, molecular mechanisms underlying these phenomena and their interrelationship, if any, can provide insight for developing new therapeutic strategies.  The prime focus of my lab is to know the mechanism of drug resistance  and the biology of this microorganism with special emphasis on regulatory/secretory protein(s) involved in the process of signal transduction.  Besides this, we have also concentrated towards identification/characterization of essential gene(s) in this bacterium.  Thus, our long-term goal is to utilize the results of basic research towards identifying new drug target(s), which may lead towards development of novel antimycobacterial agents.

Besides work with mycobacteria, we were successful in developing a heterologous expression system for androgen receptors in yeast (Saccharomyces cerevisiae), which could be utilized as a rapid, easy and sensitive screen for identifying novel androgen agonists. The need for short half life androgens in clinical settings to combat wasting in patients with AIDS and other chronic diseases like cancer is well documented and it is in this context our work is of considerable significance.  Furthermore, we have shown that this yeast-based system could be utilized for detection of mutation in the steroid receptor gene that impairs normal receptor function. Therefore, such a function-based assay has several potential advantages over existing methods for detecting mutations that cannot distinguish between polymorphisms and missense mutations. Another facet of our work has been to address the cross talk between different signalling pathways in steroid hormone regulated gene expression.  Our results clearly indicated for the first time that the steroid-dependent activation of rat androgen receptor by the modulators of kinase-phosphatase pathways could be recapitulated in yeast.  Therefore, recapitulating this phenomenon in yeast would definitely provide an efficient means for genetic analysis of the cross-talk between modulators of protein phosphorylation and steroid receptors for a better understanding, especially in clinical settings, like androgen resistance, prostate cancer etc.


Significant recognition: Awards, fellowships, international funding of distinction, technologies transferred/licensed etc.:

  • Research Associate (Postdoctoral) awarded by CSIR, New Delhi, India.

  • Visiting Associate in the Fogarty International Programme, NIH, Bethesda, USA.

  • National Biosciences Award for Career Development (DBT, Govt. of India, New Delhi).

  • Fellow, National Academy of Sciences, India.

  • Member, Guha Research Conference.

  • Member, American Society of Biochemistry and Molecular Biology, USA.

  • Life member, Society of Biological Chemists, India.

Selected list of Publications and Patents:

  • Banerjee SK, Bhatt K, Rana S, Misra P and Chakraborti PK.  Involvement of an efflux system in mediating high level of fluoroquinolone resistance in Mycobacterium smegmatis. Biochem Biophys Res Commun, 226: 362 - 368, 1996.

  • Banerjee SK, Misra P, Bhatt K, Mande S,  and Chakraborti PK.  Identification of an ABC transporter gene that exhibits m-RNA level overexpression in fluoroquinolone resistant Mycobacterium smegmatis.  FEBS Letters, 425: 151 - 156, 1998.

  • Rana S, Bisht D and Chakraborti PK.  Activation of rat androgen receptor by androgenic ligands is unaffected by anti-androgens in Saccharomyces cerevisiae.  Gene, 209: 247 - 254, 1998.

  • Chakraborti PK , Banerjee SK, Bhatt K,  Misra P and Rana S.  Mechanism of drug resistance: a novel role of phosphate specific transporter.  In ‘Drug resistance: mechanism and management’ (Singhal RL and Sood OP eds.), pp. 22 - 25, Communicore (Ranbaxy Science Foundation), 1998.

  • Rana S, Bisht D and Chakraborti PK.  Synergistic activation of yeast expressed rat androgen receptor by modulators of protein kinase A.  J Mol Biol, 286: 669 - 681, 1999.

  • Chakraborti PK , Bhatt K, Banerjee SK, Misra P.  Role of ABC importer in mycobacterial drug resistance. Bioscience Reports, 19: 293-300, 1999.

  • Banerjee SK, Bhatt K, Misra P and Chakraborti PK.  Involvement of a natural transport system in the process of efflux mediated drug resistance in Mycobacterium smegmatis.  Molecular and General Genetics, 262: 949 - 956, 2000.

  • Bhatt K, Banerjee SK, and Chakraborti PK. Evidence that phosphate specific transporter is amplified in a fluoroquinolone resistant Mycobacterium smegmatis.  Eur J Biochem, 267: 4028 - 4032, 2000.

  • Sarin J, Aggarwal S, Chaba R, Varshney G and Chakraborti PK.  B subunit of phosphate specific transporter from Mycobacterium tuberculosis is a thermostable ATPase.  J Biol Chem, 276: 44590 -44597, 2001.

  • Chaba R, Raje M, and Chakraborti PK.  Evidence that an eukaryotic type serine/threonine protein kinasefrom Mycobacteriumtuberculosis regulates morphological changes associated with cell division.  Eur J Biochem, 269: 1078 - 1085, 2002.

  • Sarin J, Raghava GPS and Chakraborti PK.  Intrinsic contributions of polar amino acid residues towards thermal stability of an ABC-ATPase of mesophilic origin.  Protein Sci, 12: 2118 - 2120, 2003.

  • Tiwari S, Radha Kishan KV, Chakrabarti T and Chakraborti PK.  Amino acid residues involved in autophosphorylation and phosphotransfer activities are distinct in nucleoside diphosphate kinase from Mycobacterium tuberculosis.  J Biol Chem, 279: 43595-43603, 2004.

  • Gupta S, Chakraborti PK, Sarkar D.  Nucleotide-induced conformational change in the catalytic subunit of the phosphate-specific transporter from M. tuberculosis: Implications for the ATPase structure.  Biochim Biophys Acta, 1750: 112-121, 2005.

  • Kumar P, Verma A, Saini AK, Chopra P, Chakraborti PK, Singh Y, Chowdhury S.  Nucleoside diphosphate kinase from Mycobacterium tuberculosis cleaves single strand DNA within the human c-myc promoter in an enzyme-catalyzed reaction.  Nucleic Acids Res,  33:2007-2714. 2005.

  • Saxena R and Chakraborti PK.  The carboxy-terminal end of the peptide deformylase from Mycobacterium tuberculosis is indispensable for its enzymatic activity.  Biochem Biophys Res Commun,  332 :418-25, 2005.

  • Saxena R and Chakraborti PK.  Identification of regions involved in enzymatic stability of peptide deformylase of Mycobacterium tuberculosis.  J. Bacteriol,  187:8216-8220, 2005.

  • Thakur M and Chakraborti PK.  GTPase activity of mycobacterial FtsZ is impaired due to its trans-phosphorylation by the eukaryotic-type Ser/Thr kinase, PknA.  J Biol Chem. 281:40107-40113, 2006.

  • Thakur M, Chaba R, Mondal AK and Chakraborti PK.  Inter-domain interaction reconstitutes the functionality of PknA, a eukaryotic-type Ser/Thr kinase from Mycobacterium tuberculosis. J Biol Chem, 283:8023-8033, 2008.

  • Thakur M and Chakraborti PK. Ability of PknA, a mycobacterial eukaryotic-type serine/threonine kinase to transphosphorylate MurD, a ligase involved in the process of peptidoglycan biosynthesis. Biochem J, 415: 27-33, 2008.

  • Saxena R, Kanudia P, Datt M, Dar HH, Karthikeyan S, Singh B and Chakraborti PK. Three consecutive arginines are important for the mycobacterial peptide deformylase enzyme activity. J Biol Chem, 283: 23754–23764, 2008.

    Patent:

  • Simons SS, Jr., Chakraborti PK, Garabedian MJ and Yamamoto KR.  US patent no. 5,215,916 (granted on June 1, 1993).

  • Saxena Rahul and Chakraborti PK.  Patent application filed (India: 1763 DEL 200, August 2, 2006; PCT: PCT/IB2007/002144, July 27, 2007; US: 11/888,610, August 1, 2007).

Present group members:

  • Haider H. Dar
  • Pavitra Kanudia
  • Payal Mittal
  • Sandeep Ravala.
  • Sanjay Kumar
  • Ghansham S. Yadav
  • Jankey Prasad
  • Garuv Sharma
  • Kanchan Kumar

Past group members:

  • Dr. Seema Rana
  • Dr. Kamlesh Bhatt
  • Dr. Sanjiban Banerjee
  • Dr. Jyoti Sarin
  • Dr. Rachna Chaba
  • Dr. Sangeeta Tiwari
  • Dr. Rahul Saxena
  • Dr. Vijayabharthi Srinivasan
  • Dr. Meghna Thakur
Postdoctoral research:
  • Drs..Parimal Misra
  • Deepa Bisht
  • Sita Aggarwal
  • Swapna Thomas
  • Jyotsna Kumari
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