Malaria remains one of the world’s deadliest parasitic diseases. Our team’s research has made fundamental discoveries in novel host-pathogen interactions and examined their molecular and structural mechanisms to drive rational design of new therapies against malaria.
The Tham lab studies parasite adhesins required for entry into human red cells, parasite surface proteins that bind to human complement proteins for immune evasion and novel parasite proteins involved in fertilisation in the mosquito.
Our work intersects with the fields of structural biology, nanobody technology, immuno-epidemiology and molecular parasitology. The overarching aim is to rationally design and generate new inhibitors or antibodies that block these interactions and stop recurrent malaria infection in humans and block transmission from mosquitoes.
To understand mechanisms of malaria parasite entry and fertilisation for the development of novel interventions to stop infection and transmission of the malaria parasites.
Surface-associated proteins play critical roles in the Plasmodium parasite life cycle and are major targets for vaccine development. The 6-cysteine (6-cys) protein family is expressed in stage-specific manner throughout the parasite life cycle and conserved across Plasmodium species, but the precise function of many family members is still unknown.
The main aims of this project are to dissect the roles of 6-cys family during the parasite life cycle. We have nanobodies against several 6-cys proteins to examine the cellular localization, to identify interacting partners and neutralizing antibodies against parasite blood stage invasion and transmission studies.
Being an obligate intracellular parasite, malaria parasites have to invade red blood cells in order to survive within the human host. One essential step within invasion is the recognition of human red blood cells by malaria parasites, a process involving an intimate interaction between parasite adhesins and red blood cells receptors. This project will identify novel parasite adhesins involved in red blood cell recognition and how they function in the dynamic process of entry. We can exploit this information to rationally design inhibitors or antibodies to prevent malaria parasite invasion into human red blood cells.
Our lab is interested in identifying novel parasite adhesins involved in red blood cell recognition and how they function in the dynamic process of parasite entry.
This project will involve characterisation of human monoclonal antibodies to identify neutralising antibodies that effectively inhibit parasite invasion. We will use a wide range of biochemical, structural and molecular techniques to characterise the mechanism of inhibition. We can exploit this crucial information to rationally design a potential vaccine to prevent malaria parasite invasion into human red blood cells.
Nanobodies are single domain antibodies isolated from camelids or cartilaginous fish. They are the smallest naturally derived antigen-binding fragment and only one-tenth the size of conventional antibodies. Nanobodies are used as therapeutics and research tools due to their small size, high antigen binding affinity, solubility and increased stability across temperature and pH.
This project will involve characterization of nanobodies against malaria proteins to identify antibodies that effectively inhibit parasite fertilisation and subsequent transmission from mosquito to human. We will use a wide range of biochemical, structural and molecular techniques to characterize the mechanism of inhibition. The results from this project identify new potential therapeutics to block transmission.