Genetically Predisposed Individuals

I am a basic biochemist and interested in events that takes place in cancer biology at the molecular level. I found interesting that RNA biology and its under lying events plays a crucial role in the afore mentioned. My primary goal is to understand the basic and fundamental mechanisms of protein synthesis and determine how these mechanisms contribute to both normal and disease states, in particular, Celiac Disease and cancer. The major mechanism to regulate protein synthesis is at the step of initiation. Initiating translation of a messenger RNA requires recruiting the ribosome to the mRNA and positioning it at the initiator codon (AUG). The major mechanism for these processes is called the cap/scanning model whereby the cap-binding protein binds the very 5' end of the mRNA, the 7 methyl guanosine triphosphateand recruits the translational machinery including the 40S ribosome. The ribosome, in turn, migrates or scans along the 5' leader until it encounters an AUG in a proper context. An alternative and less well understood mechanism is the recruitment of the ribosome by the 5' leader.

These regions downstream of the cap structure are called internal ribosomal entry sites (IRESes). IRESes have been best studied under various clinical conditions and in a subset of viruses including poliovirus and Hepatitis C. To date, only a small percentage of eukaryotic mRNAs have been shown to contain an IRES and the mechanism and function of these eukaryotic IRESes is not well understood. It is proposed that conditions that inhibit or down-regulate cap-dependent translation maintain or up-regulate IRES-dependent translation. These same conditions contribute to cancer. My ultimate research goal is to identify IRESes in mRNAs that code for proteins that are essential for the etiology that contribute to carcinogenesis (Aurora A Kinase). In addition, i am interested in examining the regulation (or mis-regulation) of the above IRESes in part by identifying intracellular signaling pathways that potentially lead to the post-translational modification of specific RNA-binding proteins in culture as well as the creation of transgenic animals which can be well used for my research as well as for the future generation. Celiac disease (CD) is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically predisposed individuals. Before activating the immune system, gluten peptides are transferred by the epithelial barrier to the mucosal lamina propria, where they are deamidated by intestinal tissue transglutaminase

2. When it comes to celiac disease in India the research is mainly focused on clinical rather than the pharmacological. Many journals have been published but most of them have reported the clinical case studies. These is no retrospective study published till date and the number of subjects affected or the underlying facts behind has not yet to be brought to the lime light for the benefits of the public.