Home | Site Map | Contact Us | Hindi Version
About Us Services Research Publications Group Leaders RTI Act Awards & Honours Careers Web Mail
 
Dr. Prem S. Kaushal
Research
Group
Publications
 
Home >> Structural Biology
Structural Biology
Research Interests

1. Protein synthesis in Plasmodium falciparum

Plasmodium falciparum (Pf) is an intracellular obligate human parasite that causes the most lethal form of malaria. Thus, malaria imposes an enormous burden on global human health. Owing to the emergence of parasite resistance to front-line drugs, there is an urgent need to find new antimalarial drug targets and improve the efficacy of presently used drugs.

The plasmodium parasite has three genomes present in the nucleus, mitochondria and apicoplast with its own transcriptional and translational machinery. Thus P. falciparum possesses three active protein synthesis sites: (i) the cytoplasmic ribosome, responsible for the vast majority of protein synthesis; (ii) the mitochondrial ribosome, responsible for synthesizing three proteins, cytochrome b and two subunits of cytochrome oxidase; and (iii) the ribosome residing inside a non-photosynthetic plastid, termed the apicoplast. The apicoplast ribosome synthesizes 18 ribosomal proteins, an elongation factor Tu (EF-Tu), subunits of its RNA-polymerase, a CIpC-like protease, and the SufB protein, a component of the Fe-S cluster assembly The Pf apicoplast translational machinery possesses several unique features including the composition of its ribosome, which contains a lesser number of ribosomal proteins (16 in the small ribosomal subunit [SSU], and 21 in the large ribosomal subunit [LSU]), as compared to the bacterial ribosome (21 in SSU and 34 in LSU). In addition, the translation factors carry apicoplast specific insertions and extensions ranges from 8 to 115 amino acid long. The apicoplast protein translation machinery is an attractive anti-malarial drug target because of its prokaryotic origin and its crucial importance in the survival of the parasite.

My lab's interest is to applying an integrated structural biology approach to illustrate the architecture of the Pf apicoplast ribosome and molecular mechanism of interactions between the Pf apicoplast ribosome and its translational factors, and molecular details of interactions of existing drugs.

2.Mechanism of dormancy ini Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) is the causative agent of one of the most deadly bacterial diseases, tuberculosis (Tb). Tb remains a major health threat for the human race. In 2015 alone, Tb-related diseases have killed nearly 1.5 million peoples worldwide, including about 0.3 million people in India. The Mtb has emerged with multi-drug resistant (MDR-Tb) and extensive-drug resistant (XDR-Tb) strains towards currently used drugs.

MTb possesses a unique mechanism to establish a latent tuberculosis infection (LTBI), the dormancy state, capable of its long persistence in the host, even in the presence of functional host immune response. An estimated one third of the world.s population has LTBI and eradication of tubercle bacilli in latent lesion by current drugs has proved to be inefficient. The molecular mechanisms of Mtb entry into dormancy and its maintains of dormancy state remain vaguely known. The dormancy survival regulon (DosR regulon) encodes nearly 48 genes that appear to play crucial roles in dormancy.

My lab's goal is to better understand the life cycle of the Mtb pathogen in its dormancy sate, by illustrating the role of all 48 genes that are expressed during pathogen's dormancy.

Research techniques

1. X-ray crystallography

2.Cryo- electron microscopy

3.Molecular modelling and docking

4.Molecular dynamic simulations

5.Ribosome and protein biochemistry

Contact Information
Email: kaushal<at>cdfd.org.in
Phone: +91-40-24749414
Fax: +91-40-24749448
Last updated on: Tuesday, 30th May, 2017

Copyright @ 2008 CDFD.