Utilizing biochemical and functional genomic approaches to uncover key host invasion receptors in plasmodium vivax

The National Institute of Allergy and Infectious Diseases awarded the President and Fellows of Harvard College, operating through Harvard T.H. Chan School of Public Health, $149,163 on September 27, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855, Assistance Listing designation F31AI197660).

The award funds identification of essential reticulocyte host receptors for Plasmodium vivax invasion using biochemical and functional genomic approaches. The research employs CRISPR/Cas9-based manipulation of red blood cell membrane proteins to uncover ligand-receptor interactions that the parasite uses to invade host cells. While the Duffy antigen receptor for chemokines (DARC) was the first identified essential receptor, Plasmodium vivax uses multiple invasion pathways that remain poorly understood. This work aims to identify those additional essential interactions to inform development of therapeutic interventions and vaccine candidates beyond the current major vaccine candidate, PvDBP.

Performance runs through August 31, 2029, with work conducted in Boston, Massachusetts.

Abstract

Malaria parasites infect red blood cells (rbcs), within which they proliferate to cause disease in a continuous cycle of invasion, growth, and egress from one host RBC to another. Free merozoite forms of the parasite use ligand-receptor interactions to invade rbcs within which they grow and proliferate. Plasmodium vivax, a major parasite species that causes malaria in humans, exclusively invades reticulocytes, the youngest of rbcs, through specific ligand-receptor interactions. The duffy antigen receptor for chemokines (darc), a blood group antigen on the RBC surface, was the first identified essential receptor for p. Vivax and is bound by the parasite invasion protein p. Vivax duffy binding protein (pvdbp). Pvdbp is now a major vaccine candidate, but IT is known that p. Vivax uses multiple receptors to invade host cells, known as invasion pathways, that are poorly understood. Here, i propose to identify essential reticulocyte host receptors for p. Vivax invasion using biochemical and functional studies. This work is based on the crispr/CAS9-based manipulation of RBC membrane proteins. The identification of essential ligand-receptor interactions for p. Vivax invasion is crucial for informing the development of therapeutic interventions.