Project details

The main aim of this project is to dissect the roles of 6-cysteine proteins, a family of important surface proteins in malaria parasite Plasmodium. To do this, we will use nanobodies, which are diminutive antibodies found in alpacas, llamas and camels. Nanobodies have been used as therapeutics and research tools due to their small size, high antigen binding affinity, solubility and increased stability across temperature and pH.  

We will characterise nanobodies against the malaria proteins to inhibit parasite invasion, transmission or growth across the whole malaria lifecycle. We will use a combination of gene-editing, biochemical and structural techniques to characterise the mechanism of nanobody inhibition. The results from this project will identify new potential vaccine candidates against malaria. 

Skills:

Phage display, protein purification, nanobody characterisation, protein-protein interactions, parasite culturing, CRISPR/Cas9, imaging 

References:

• Lyons, Front. Cell. Infect. Microbiol. 2022 (996).  
• Dietrich, FEMS microbes 2022 (3). 
• Dietrich, Biochem J. 2021 478(3):579-595. 

About our research group

Malaria remains one of the most widespread parasitic diseases in the world. More than 40 per cent of humans are under the risk of contracting this devastating disease caused by six species of Plasmodium parasites, of which Plasmodium falciparum is the deadliest.  

We want to understand how malaria parasites engage human receptors and interact with our immune system. We aim for a deeper understanding on the molecular mechanisms used by malaria parasites to infect humans and mosquitoes, and of parasite evasion strategies to circumvent human immune responses, so that we can use this pivotal information to develop novel therapeutics.  

References:

• Pymm and Adair, PNAS 2021 118(19) e2101918118 
• Chan, Nat Commun. 2021 12(1):1538. 
• Gruszczyk, Nature 2018 559(7712):135-139. 
• Gruszczyk, Science 2018 359(6371):48-55.