RSB Directors Seminar - Blood and guts: malaria parasite entry and transmission

Malaria remains one of the world's deadliest parasitic diseases, affecting millions of people worldwide. Malaria parasites are transmitted from person to person through the bite of an infected female Anopheles mosquito. They are exquisitely adapted for survival within the human and mosquito host. Malaria parasites enter human red blood cells to grow and replicate. Within the mosquito, malaria parasites undergo fertilisation and further development into sporozoites which are transmitted to humans through a mosquito bite.

In this seminar, I will cover our work on understanding mechanisms of malaria parasite entry and fertilisation and the development of novel interventions to stop infection and transmission of the malaria parasites.  I will present an overview of host-pathogen interactions that govern entry of malaria parasites into human red blood cells. I will focus on how Plasmodium vivax has hijacked Transferrin Receptor 1 to preferentially enter reticulocytes, which are young red blood cells.  Our results establish a structural framework for understanding how P. vivax reticulocyte-binding protein engages Transferrin Receptor 1, which is an essential housekeeping protein for iron uptake, and the molecular mechanism of inhibitory antibodies that block parasite entry, providing important information for the design of novel vaccine candidates against P. vivax. I will conclude with our new projects on using nanobodies to block malaria parasite transmission in mosquitoes.

Professor Wai-Hong Tham received her PhD from Princeton University. She is currently Joint Head of the Infectious Diseases and Immune Defence Division and co-Chair of the Biologics Initiative at the Walter and Eliza Hall Institute. She has made fundamental discoveries in novel host-pathogen interactions and examined their molecular and structural mechanisms to drive rational design of new therapies against infectious diseases for malaria and COVID-19. Her work intersects with the fields of structural biology, immuno-epidemiology and molecular parasitology. For her contribution to understanding malaria parasite invasion, she has received the 2020 International Award Biochemistry Society, 2019 and 2011 Eureka Prize for Infectious Diseases Research (team prize), the 2017 David Syme Research Prize and the 2018 Burnet Prize. In 2020, she led a highly collaborative program between medical research institutes and industry to develop antibody-based therapies against COVID-19.