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Biennial Report 2005-2007 - Saha Institute of Nuclear Physics

Biennial Report 2005-2007 - Saha Institute of Nuclear Physics

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Biophysical Sciences 205<strong>of</strong> the plasma proteins with different percentages <strong>of</strong> ammonium sulfate to preferentially depleteserum albumin and subsequently visualize more spots in the proteomic pr<strong>of</strong>iles.Sutapa <strong>Saha</strong>, Dipankar Bhattacharya, Subrata Banerjee, Debashis Banerjee†, Sharmila Chandra†,Abhijit ChakrabartiSG6.1.1.17 Leukemia: a defect in “growing up”We are involved in understanding the role <strong>of</strong> cell cycle proliferation, the self renewal pathwaysin controlling differentiation or“growing up” <strong>of</strong> human hematopoietic stem cells. We have earlierdeveloped a mini EBV vector which carries small interfering RNA(siRNA) for the BCR-ABL geneinvolved in chronic myeloid leukemia. This vector has now been further engineered to transfervarious cell cycle genes and cell signalling molecules into hematopoietic stem cells (CD34+) grownin vitro. The role <strong>of</strong> the immune system in controlling such aberrant proliferation is being studiedin leukemia and various other cancers. Transcriptional regulation <strong>of</strong> HLA class I gene by variousmiRNA and human EBV genes are being investigated in mesenchymal-epithelial transition <strong>of</strong> cancerand its invasiveness.Amitava Sengupta, Subrata BanerjeeSG6.1.2 Macromolecular Crystallography6.1.2.1 A high resolution crystal structure <strong>of</strong> cyclophilin from Leishmania donovani:Elucidation <strong>of</strong> its interactions with drugs and proteinsThe crystal structure <strong>of</strong> cyclophilin from Leishmania donovani (LdCyp) has been determined andrefined at 1.97 esolution to a crystallographic R factor <strong>of</strong> 0.178 (Rfree = 0.197). The structure wassolved by molecular replacement using cyclophilin from Trypanosoma cruzi as the search model.LdCyp exhibits complete structural conservation <strong>of</strong> the cyclosporin-binding site with respect to thehomologous human protein, as anticipated from LdCyp-cyclosporin binding studies. Comparisonswith other cyclophilins show deviations primarily in the loop regions. The solvent structure encompassingthe molecule has also been analyzed in some detail. The coordinates <strong>of</strong> this high resolutionstructure were used to build homology models <strong>of</strong> different mutants to elucidate its interaction with

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