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.
1. X-ray crystallography
2.Cryo- electron microscopy
3.Molecular modelling and docking
4.Molecular dynamic simulations
5.Ribosome and protein biochemistry