Our research involves functional genomics of malaria parasites using the rodent malaria model Plasmodium berghei. This work evolves around the generation of genetically modified parasites in which target genes are disrupted, tagged or mutated, providing important information on the expression, function and redundancy of gene products. We were the first in the UK to successfully establish the gene targeting technology in P. bergheiand have since applied the technology to investigate the function of many different Plasmodium genes. We have over 24yrs experience of working with this parasite model in the mouse and mosquito stages and we possess a comprehensive set of specific reagents, molecular tools, and biological protocols to facilitate this work. We successfully pioneered protein tagging with green fluorescent protein and mCherry red fluorescent protein in P. berghei, allowing studies of protein subcellular trafficking and interaction in living cells. 

Our active and longstanding research programme has two main components:

(1) The role of the subpellicular network (SPN) in malaria parasite development and infectivity. The SPN is a cortical cytoskeletal structure of apicomplexan parasites that is involved in morphogenesis, viscoelasticity and motility of apicomplexan zoites. We were the first to identify a family of unique intermediate proteins termed alveolins that are major components of the SPN, and we have shown that many have essential functions throughout the Plasmodiumlife cycle. Our current focus is on determining the molecular mechanisms by which alveolins facilitate SPN targeting, filament formation, tensile strength and locomotion.

(2) The role of the crystalloid organelle in sporogonic development of malaria parasites. The crystalloid is an enigmatic organelle found uniquely in the ookinete and young oocyst life cycle stages of malaria parasites. We were the first to identify a family of LCCL lectin domain adhesive-like proteins (LAPs) that reside in the crystalloid and demonstrate their essential roles in crystalloid biogenesis. These studies have revealed that the crystalloid is critically involved in sporogony. Our current focus is on elucidating the molecular mechanisms by which the crystalloid facilitates sporogonic development and sporozoite transmission.