Dissecting the role and the molecular mechanism of action for the PfSR25 during asexual and sexual blood stages of P.falciparum.

• Grant number: 25/04088-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2025
• End date: June 30, 2027
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Célia Regina da Silva Garcia
• Grantee: Abhinab Mohanty
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Malaria remains a leading cause of death globally, with millions of cases reported each year. The causative organism - Plasmodium sp., is becoming increasingly difficult to control due to its complex biology and growing drug resistance to clinical antimalarial regimen. Innovative approaches are required combating the spread of malaria by targeting specific proteins in the parasite. The G-protein coupled receptor PfSR25 presents itself as a candidate offering new solutions. PfSR25 is believed to play a crucial role in sensing potassium and regulating calcium signaling, both of which are essential for the parasite's intraerythrocytic invasive ability.The project aims at conducting a comprehensive localization study of PfSR25 in both normal and stress conditions using fluorescence microscopy and quantitative PCR to assess its gene expression and regulatory dynamics. Differential antimalarial susceptibility will be validated through flowcytometry and heme speciation analysis. Calcium dynamics in wild-type and PfSR25 knockout strains will be assessed to elucidate PfSR25's function as an ion sensor. Additionally, co-immunoprecipitation and phosphoproteomics will identify PfSR25's molecular partners and the impact of potassium shifts on protein phosphorylation. Understanding PfSR25's localization, interaction partners, and response to antimalarials will provide critical insights into its mechanistic role and potential for therapeutic targeting, contributing to the global fight against malaria.