Transcription is a complex process. It is regulated at various stages by several important proteins that interact with the DNA or RNA Polymerase (RNAP)the key enzyme/protein in transcription. Key to this regulation are RNAP and regulatory protein complexes. Malfunction of these complexes is frequently implicated in diseases such as cancer, autoimmune disease, cardio vascular disease, diabetes, infectious disease etc. In order to understand the basis of these malfunctions, we have to study these macromolecules and the interacting partners at the molecular level. By studying their structure at the molecular level, we will be able to gain knowledge about their interaction and the mechanism that leads to their function or malfunction. Structural biology methods are excellent tools to accurately understand the structural information that will define the interactions and functional mechanisms of their component protein or their subunits. Single particle cryo electron microscopy and Protein crystallography along with other biophysical techniques are excellent tools to study these molecular machines the proteins. By combining structural information of different functional states, together with other biochemical and/or biophysical data, we aim to get a detailed snap-shot of the function of these proteins during its functional state, that will reveal their intricate mechanisms.
Our lab is currently focusing on structural studies of protein complexes involved in Mycobacterium tuberculosis and DNA damage repair in both prokaryotes and eukaryotes. The RNAP, the central player in transcription is an important target for novel antibiotics. We aim to fully understand the mechanisms by which transcription is regulated. Towards this we use two principle techniques viz., Protein Crystallography(PX) and Cryo Electron microscopy(CryoEM) along with bioinformatics and range of other biophysical (DLS, MALS, CD, ITC, SPR, Fluorescence Spectroscopy), biochemical and molecular biology techniques.
Our Natesh Structural Molecular Biology laboratory (NSMB) Lab is located in the School of Biology, Indian Institute of Science Education and Research Thiruvananthapuram.