Enviromental triggers of gametocyte induction in malaria parasites

In recent years global efforts to control malaria have stalled as the upper limit of vector control appears to have been reached. Coupled with the emergence of drug resistance, there is a significant risk that the gains in malaria control achieved in the past decades may be reversed. Targeting malaria transmission is a key strategy that can reduce both malaria cases and limit the spread of drug resistance. Critical to malaria transmission is the process of sexual commitment resulting in the production of gametocytes. The Marti and Preiser groups have independently identified host derived signals that are sensed by the malaria parasite resulting in changes in sexual commitment rates. While the Marti group has focused on metabolic sensing the Preiser group has identified host immune responses as potential signals. Strikingly, we have some preliminary evidence that there is a convergence of these different signals that ultimately trigger gametocyte induction. To achieve this, already generated parasite lines will be used that have critical disruptions in potential regulatory proteins identified by the two labs and compare their ability to respond to different environmental signals. Downstream analysis will focus on quantifying cellular/transcriptional responses and evaluate the overall impact on gametocyte development. The proposed work if successful will provide critical preliminary data that can form the basis for a much larger collaboration going forward. Moreover, standardization of protocols between the two labs will ensure that future data generated is more easily comparable. In addition, understanding how the parasite is able to sense host signals will provide not only important fundamental insights about parasite biology but would be of value for intervention studies focusing on transmission blocking approaches.

Project details

Basic Science

Apr 2024 — Jul 2024

$11,268

Switzerland