Life Sciences & Biotechnology
Title : | Functional characterization of Plasmodium falciparum exported proteins and associated phosphorylation events. |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Parasitology and Molecular Biology |
Principal Investigator : | Dr. Ankit Gupta, All India Institute of Medical Sciences, Raebareli, Uttar Pradesh |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | guptaankitbiochem07@gmail.com |
Details
Executive Summary : | Parasites traffic various proteins in the host compartment to create a suitable habitat for their multiplication and escape from host immunity. The level of phosphorylation in the infected erythrocyte is significantly increased upon parasite invasion. The study hypothesizes that exported Ser/Thr kinases phosphorylate these proteins, which are linked to key functions such as nutrient transport and cytoadhesion. The available data on phosphorylation of RhopH complex proteins will be revalidated through a reverse genetics approach, answering the debate between PSAC and NPP theory of nutrient transport across the host erythrocyte membrane. Three putative P. falciparum exported proteins (PF3D7_0718100, FEST kinase; PF3D7_1121900, STPK; PF3D7_1149100, PfExP) will be prioritized based on available data and significant hits/unique peptides obtained through LC/MS-MS analysis of infected erythrocyte membrane fraction. The kinase domain of FEST kinase, complete STPK, and PfExP proteins will be expressed as recombinant proteins, and their functional characterization will be carried out. The endogenous gene encoding these proteins will be disrupted using CRISPR-Cas9, and transgenic parasites will be generated for conditional knockdown of these proteins. The growth rate and functional characterization of these phosphodeficient transgenic parasites will be compared with wild-type parasites. |
Total Budget (INR): | 50,93,880 |
Organizations involved