Institute of Microbial Technology,
Sector 39 A, Chandigarh 160036
Telephone : +91-172-2636680 (Extn. 3249) ;  
Fax   : +91-172-2690585
Email  : kanak@imtech.res.in

Our group is mainly involved in fundamental and applied studies on microbial hemoglobins and clot-dissolving proteins. Our research is mainly directed to understand structure function aspects, molecular mechanism of protein-protein interactions and genetic regulation of these microbial proteins to understand their cellular functions and develop new derivatives for therapeutic usage and biotechnological applications.

Hemoglobins are generally considered oxygen binding and storage proteins. Our research interest is focused on understanding the role of hemoglobins present in microbial world. Studies conducted in our laboratory have unraveled several novel functions of microbial hemoglobins in cellular metabolism including their role in facilitation of cellular respiration, electron transport, modulation of redox state of cells and stress management demonstrating diversity in their cellular functions. Our current research aims to understand how distinct structural organization, conformation of heme pockets and cellular localization of microbial hemoglobins modulate their interactions with different cellular partners and allow them to perform multiple cellular functions. Our recent studies on novel hemoglobins of Mycobacterium tuberculosis have provided some new insights into the functions of hemoglobins in cellular metabolism and pathogencity of tubercle bacillus that include role of hemoglobins in nitric oxide detoxification through a unique mechanism, and facilitation of cellular respiration in conjunction with terminal oxidases. These findings along with our other studies provided vital clues for the crucial involvement of oxygen binding proteins in intracellular survival and pathogenicity of tubercle bacillus. Our current studies are directed towards understanding the role of different hemoglobins of Mycobacterium tuberculosis at molecular level to explore their distinct functions during pathogenic and latent phase.

Another area of interest in our laboratory is to understand molecular mechanisms of function of microbial clot-dissolving agents taking Staphylokinase as model protein. These studies are focused on understanding the molecular mechanism of substrate specificity change introduced in human plasminogen by staphylokinase interactions. A high yielding recombinant strain and a novel expression system has been developed in our laboratory for the large-scale production and purification of recombinant stapylokinase and this process has been transferred to a pharmaceutical company for further development for commercial production. Current focus of our laboratory is to enhance the pharmacological benefits of Staphylokinase by developing new derivatives for site-specific modification to increase its plasma half-life, thermal stability and lower immune reactivity.

• Fellow of National Academy of Sciences
  
  
• Elected member of Guha Research Council
  
  
• Awarded DST (India)-NSF(USA) sponsored bilateral INDO-US research grant  (1999-2003)
  
  
• Awarded DST (India)-NSF(USA) sponsored bilateral INDO-US research grant (2004-2008)
  
  
• Awarded International European Commission research grant on health (2008-2011)
  
  
• Technology transferred/licensed to Stride Arcolabs  for the production of recombinant Staphylokinase

List of selected Publications:

• Lama, A., Pawaria, S., Bidon-Chanol, A., Anand, A., Arya, S., Marcelo, M., Dario, E., Javier, F. and Dikshit, K. L*. (2009)  Role of Pre-A motif in nitric-oxide scavenging of hemoglobin, HbN, of Mycobacterium tuberculosis.J. Biol. Chem. 284:14457-14468.
  
  
• Pawaria, S., Lama, A., Raje, M. and Dikshit, K. L*. (2008) Responses of Mycobacterium tuberculosis hemoglobin promoters to in vitro and in vivo growth conditions. Appl. Environ. Microbiol., 74; 3512-3522.
  
  
• Pawaria, S., Rajamohan, G., Gambhir, V., Lama, A., Varshney, G. C. and Dikshit, K. L* (2007) Intracellular growth and survival of Salmonella enterica serovar Typhimurium carrying truncated hemoglobins of Mycobacterium tuberculosis. Microb Pathog.  42, 119-128.
  
  
• Lama, A., Pawaria, S., and Dikshit, K. L* (2006) Oxygen binding and NO Scavenging properties of truncated hemoglobin, HbN,of Mycobacterium smegmatis.  FEBS Lett. ;580:4031-4041.
  
  
• Dahiya, M., Rajamohan, G and Dikshit, K. L* (2005) Enhanced plasminogen activation by staphylokinase in the presence of streptokinase beta/betagamma domains:  plasminogen kringles play a role. FEBS Lett. 579: 1565-72.
  
  
• Rajamohan G., Dahiya M., Mande, S.C. and Dikshit, K. L.* (2002) Function of 90-loop  90-loop (Thr90-Glu100) region of staphylokinase in plasminogen activation probed through site-directed mutagenesis and loop deletion.    Biochem. J. 365: 379-389.
  
  
• Pathania, R., Navani, N., Gardner, A. M., Gardner, P. R. and Dikshit, K. L.* (2002) Nitric oxide scavenging and detoxification by the Mycobacterium  tuberculosis  haemoglobin, HbN in Escherichia coli. Mol  Microbiol. 45: 1303-1314.
  
  
• Pathania, R., Navani, N. K., Rajamohan G., and Dikshit, K. L* (2002) Mycobacterium tuberculosis hemoglobin HbO associates with membranes and  stimulates cellular  respiration of recombinant Escherichia coli.  J. Biol Chem.  277 ; 15293-302.
  
  
• Kaur, R., Pathania, R, Sharma, V, Mande, S. C. and Dikshit, K. L*. (2002) Chimeric Vitreoscilla hemoglobin (VHb) carrying a flavoreductase  domain relieves nitrosative  stress in Escherichia coli : new insight into the functional role of VHb  Appl. Environ. Microbiol. 68, 152-160.
  
  
• Ramandeep, Hwang, H. Y., Raje, M., Kim, K. J., Stark, B. C., Dikshit, K. L*.Webster, D. A. (2001) Vitreoscilla hemoglobin. Intracellular localization and binding to membranes. J. Biol Chem. 276: 24781-9.
  
  

Patents:

• Dikshit, K. L. , Vyas, V. V. Vyas, Mahajan, R., Kaur, J., Pratap, J. Nihlani, D. and Sahni G  “ A process for the preparation of extracellular streptokinase and itsanalog”  (1727/DEL94/ 183828 ).
  
  
• VVyas, V. V., Rajamohan G., Kaur Ramandeep and Dikshit K. L. “ An improved process for the production of intracellular recombinant streptokinase”(US Patent No. 7189557 dated 13/03 / 2007)
  
  
• Rajamohan G., Dahiya M, Pathania, R. and Dikshit, K. L. “ A novel process for Oxygen dependent production of recombinant Staphylokinase “(NF 268 /02/ US patent  pending/ 0268NF2002/ZA grantted)
  
  
• Satish Singh and Kanak L. Dikshit “ Modified staphylokinases and their PEG (Polyethylene Glycol) conjugated forms” (provisional patent application filed; Ref. 0171 NF 2008)

Senior Research Fellow

• Mr. Arvind Ananad
• Miss Swati Arya

Research Fellow

• Mr. Sanjay Gupta
• Mr. Satish Singh
• Mr. Sandip Singh
• Miss Deepti Sethi

Senior Technical Assistant

• Mr. Muthu Krishnan

Project Assistant

• Miss Renu Goel
• Miss Simarbir Kaur
• Miss Preeti Raju