Structural Parasitology

INFECTIOUS DISEASES / Parasitic Diseases

Research Interests

Crystallography, Aminoacyl-tRNA synthetases, Inhibitor discovery

Description of Research

The laboratory takes a multi-disciplinary approach towards understanding malaria parasite proteins. The Group aims to highlight the principles that govern biological functions of key parasite proteins. Towards this end, we rely extensively on bioinformatics, biochemistry, cell biology, molecular biology, parasitology and protein crystallography. Using multi-disciplinary approaches, we have been successful at elucidating structure-function relationships for several crucial parasite proteins, and we hope that these analyses will guide therapeutic developments against malaria. We are interested in dissecting the protein translation machinery within the parasite. Specifically, our focus is on (1) aminoacyl-tRNA synthetases and (2) D-amino acid tRNA deacylase. Several specialized parasite proteins perform DNA compaction and we are working on two such proteins called Nucleosome Assembly Proteins (Pf-NAPz). These two proteins interact with other essential parasite proteins like histones to assemble and disassemble nucleosomes. P. falciparum NAPz are important for cellular activities like DNA repair, DNA recombination and transcription. We have identified a role for PfNAPz in histone transport and nucleocytoplasmic shuttling.  The other major interest in the lab is on structure-based inhibitor discovery through in silico screening of various small molecule libraries against aminoacyl-tRNA synthetases. Several compounds are being tested for parasite inhibition and to assist in rational drug design.

Studies from the Group have recently carried out structural analyses of the malaria parasite aminoacyl-tRNA synthetases which provides new avenues for antimalarial drug discovery. (Chhibber-Goel et al., Protein Sci 2021).

Recent Publications