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Chemical and Synthetic Biology Discovering apoptotic cell death inducers and dissecting apoptosis using a chemical biology approach: The project aims to discover tumor cells selective apoptotic cell death inducing agents and understand the differential regulation of cell death in normal and cancer cells using a chemical biology approach. Diverse small molecule libraries will be made using synthetic and combinatorial chemistry techniques and screened in cultured cells for apoptosis induction. Using probe reagents prepared from the apoptosis inducers, cellular target identification and mode of action of the bioactive molecules will be investigated using a combination of biochemical, genomics and organic chemistry techniques.Principal Investigator: RK Sunil Singh
Developing cell death inducing siRNAs as anticancer agents: The overall goal of this project is to identify apoptosis inducing small interfering RNAs and develop them as potential anticancer agents. Small interfering RNAs targeting anti-apoptotic genes such as IAPs, Bcl-2, etc. will be designed validated and those capable of inducing apoptosis in cultured cells & mouse tumor models will be identified. Apoptotic cell death inducing siRNAs will then be chemically modified in order to increase potency and nuclease stability for use in vivo. This study will help to identify and develop anticancer siRNAs for potential therapeutic applications. Principal Investigator: RK Sunil Singh
Designing, Synthesis and evaluation of anti-infective agents: The aim of this project is to design novel inhibitors against Mycobacterium tuberculosis to tackle the MDR TB as well as newly developed XDR TB. This project includes the synthesis, designing, molecular modeling and their evaluation against a panel of sensitive, multidrug resistant and extensive drug resistant strains and latent Mycobacterium tuberculosis. We intend to understand the molecular mechanism of resistance development as well as to know how Mycobacteria manipulate the host cellular machinery to weaken the host immune system (in close collaboration of Prof. Jyoti Chattopadhyaya/Uppsala University). The interaction of tuberculosis with the AIDS promoting Human Immunodeficiency Virus is a fatal mix. In the lethal conjunction, tuberculosis increases the morbidity of HIV sufferers, reducing their life expectancy, while the spread of HIV itself favors the propagation of many opportunistic infections like TB, malaria etc. About one-third of the world’s population carries latent tuberculosis infection (where Mycobacterium tuberculosis bacteria lie dormant in the body without causing disease). But, in the absence of HIV, only about 5% of them will ever progress to active disease stage. Keeping this deadly combination as a centre of this project we intend to address this problem by antisense and si-RNA approach. This project will involve identification of targets in HIV genome through whole genome wide search and developing a series of modified nucleotides which will have better selectivity, stability and ease for delivery to the cell.(Target the HIV/AIDS by siRNA approach is designed and conceptualized by Prof. Jyoti Chattopadhyaya/Uppsala University). Principal Investigator: Ram S Upadhayaya
Building a microbial chemical factory: Interest is to metabolically engineer the photosynthetic bacteria, Rhodopseudomonas palustris, to utilize methane as a sole carbon source for the production of usable hydrogen, plant monoterpenoids and vitamins. Principal Investigator: Sudeshna Kar
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