The malaria parasite Plasmodium falciparum undergoes a remarkable transformation that allows asexual stage multiplication in a human host and sexual reproduction in a mosquito vector. Gametocyte maturation represents a ‘bottle neck’ in the parasite’s development; inhibition of this process 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.
The McCarthy laboratory is interested in understanding the unique biology of the malaria parasite Plasmodium falciparum, with a particular focus on virulence and transmission. In our studies we use a combination of clinical and lab-based research to holistically investigate mechanisms of malaria disease and transmission. We use molecular and cellular biology tools such as CRISPR gene editing, proteomics, transcript analysis and super resolution microscopy to define the molecular players driving gametocyte development and transmission.
This in vitro work is complimented by the 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. This combined in vitro and in vivo approach to understanding how gametocytes mature will help speed up the development of new drugs and vaccines to combat this debilitating disease.