Dr. Timir Tripathi

Molecular and Structural Biophysics Laboratory

Current Research Interests

Characterization of liver fluke proteins for structure-based drug discovery

Our laboratory is working on the molecular and structural characterization of parasitic proteins of chemotherapeutic importance using state of the art techniques. These studies are intended to develop novel drugs/vaccines with therapeutic potential against the parasitic trematode- liver flukes. Apart from this, the work will contribute to a better understanding of the drug resistance mechanisms and novel insights into potential remedial approaches. Our long-term aspiration is to develop protein-based chemotherapeutic interventions to eradicate human sufferings, and develop therapeutics that are affordable to the developing world.

We use 2 different protein systems for our work.

1. The thiol based redox-active protein system.

2. Aminoacyl tRNA synthetases.

 

mRNA export and RNA Polymerase biology 

The export of mRNA from the cell nucleus is one of the pillars of the gene expression pathway in eukaryotes. We approach basic questions in mRNA export by studying the major mRNA export factor, Mex67 in yeast and Tap/NXF1 in mammalian cells. To study the interactions of Mex67/Tap with other export factors and nuclear pore components, we use high-resolution imaging and biochemical and biophysical techniques. 

RNAPII is thought to be central to different aspect of transcription and posttranscriptional events. The  goal of our other project is to understand the RNAPII based gene regulation. We implement two different strategies to investigate the distribution of transcription complexes and expect to get new proteins with yet unassigned function. We aim to identify several proteins which may help in regulating different stage of transcription, mRNA export and other cellular activities. Regulation of transcription is one of the most important steps that control cell growth and differentiation. Understanding the extent of gene regulation at the epigenetic level would help address and control the abnormal cellular behaviour in cancer and other diseases and will eventually contribute towards more targeted treatment strategies.

Role of solution variables in amyloidogenesis

Interest in amyloidogenesis has exploded in recent years, as scientists recognize the role of amyloid protein aggregates in neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Assembly of proteins or peptides into mature amyloid fibrils is a multistep process initiated by conformational changes, during which intermediate aggregation states such as oligomers, protofibrils, and filaments are sampled. Because of its relevance to mechanism of disease, the paths traversed during fibrillogenesis, the kinetics of the process, and the solution variables affecting the fibrillation are of considerable interest. Even though significant advances have been made to understand the intermediates formed during fibrillogenesis, still a number of question remains to be answered, like- What intermediates are observed? What are their size, structural, and morphological characteristics? What is the rate at which fibrillogenesis proceed? What solution parameters regulate the formation of fibrils? and so on. The major objective of the this work is to study in depth about the importance of physiological and quasi-physiological variables on the process of Amyloid fibrillation.