Project: Going bananas for sex
Gametocyte maturation and development is critical for survival within the host and disease transmission. Inhibition of this development would ablate disease transmission. This transformation sees an amoeboid shaped asexual stage parasite morph into a banana shaped sexual stage parasite, which is essential to disease transmission. Despite the importance of this stage of the parasite we understand very little about its unique biology. This unique shape is driven by the assembly of a membrane complex termed the inner membrane complex and the elaboration of a dense microtubule cytoskeleton that drives the unique gametocyte shape. In this project we are interested in determining the cellular and molecular players driving this shape change and how this influences survival within the host and mosquito transmission.
Our laboratory investigates the cellular mechanisms underpinning malaria parasite transmission and disease. We investigate the novel banana shaped sexual stages of Plasmodium falciparum, focused on understanding their unique biology and how this contributes to transmission. We are interested in developing and testing drugs and vaccines that may block transmission of the parasite from infected humans to Anopheles mosquitos.
Our research is aimed at understanding the unique biology of the malaria parasite Plasmodium falciparum, with a particular focus on virulence and transmission.
We are investigating:
- How parasites renovate their RBC home to drive virulence and transmission.
- How the parasite makes the banana shaped sexual blood stage gametocyte.
- How this shape helps them survive in the host and be efficiently transmitted.
- How parasites behave inside the human host in vivo.
- How effective specific drugs and vaccines are at blocking transmission of gametocytes from infected humans to Anopheles mosquitos.
In these projects, we will use CRISPR gene editing to create transgenic malaria parasites, which we will study by combing proteomics, molecular and cellular biology techniques with super resolution microscopy to define the molecular players driving gametocyte development and transmission. This in vitro work will be complimented by ex vivo examination of samples from experimental human malaria infection studies, which are focused on identifying and confirming the activity of candidate transmission blocking drugs and vaccines.
A combined in vitro and in vivo approach to understanding how gametocytes mature will inform the development of effective means of combating this debilitating disease.