Biology

Dr. Suchi Goel
Centre for Infectious Disease and Research, IISc, Bangalore

Plasmodium falciparum is known as “the strongest force for evolutionary selection in the recent history of the human genome”. Until recently it was believed that severity in P. falciparum is a function of sequestration of malaria parasites in the microvasculature through PfEMP1 binding to receptors on host cell surface receptors (also called cytoadherence) or uninfected cells (also called rosetting). However, PfEMP1 antibody that effectively disrupts rosettes of blood group O is ineffective against blood group A parasitized RBC rosettes. Since, it was known that A blood group patients have more severe malaria, it was very important to find out molecular mechanism that was elusive for last 40 years. Our studies identified that rosetting in blood group A is different from group O. A novel family of parasite protein, RIFINs are transported to the surface of infected erythrocytes and preferentially bind to group A RBCs. Interestingly, the expression of RIFIN in parasites that do not prefer any specific blood group started preferring blood group A for rosetting and also formed bigger and tighter clumps/rosettes. Though RIFIN prefers blood group A for rosetting but could also bind to sialic acid on glycophorin A for rosetting when PfEMP1 is absent, suggesting that this family is capable of using multiple receptors. Thus we for the first time demonstrated that RIFINs play fundamental role in severe form of malaria. In future, I am interested in understanding diverse roles of this family that are important for survival of the parasite inside the host and also decode various host receptor-parasite ligand interactions that are central to severe malaria phenomena.