Description
Title: "Genetic screens in a malaria parasite reveal the unusual reproductive biology of a divergent eukaryote"
Speaker: Oliver Billker, PhD
Laboratory for Molecular Infection Medicine and Department of Molecular Biology, Umeå University, Sweden
Date: Friday, May 10, 2024
Time: 12-1 pm
Location: Hybrid seminar in Hill 132 and Virtually Via Zoom
Questions? Please contact Michael Black at blackmic@upenn.edu if you have questions.
Abstract:
Malaria is caused by protozoan parasites of the genus Plasmodium, which is transmitted between hosts by a mosquito vector, causing more than half a million deaths annually, with 70% of deaths occurring in African children under the age of seven. Malaria parasites are divergent eukaryotes with a complex life cycle, whose asexual replication in erythrocytes is responsible for disease, but whose transmis-sion by mosquitoes depends entirely on sexual reproduction.
In a tractable rodent model, we have scaled up the targeted disruption of parasite genes to the point of enabling genome scale genetic screens at different life cycle stages. This has revealed how gene essentiality has evolved differently in different parts of the genome. It has also allowed us map how parasite metabolism is reor-ganized as the parasite moves between different hosts and tissues, exposing changing drug vulnerabilities throughout the life cycle.
Sexual reproduction is essential for malaria parasites to infect mosquitoes, and our screens identify hundreds of parasite genes involved in the process. An analysis of fertility genes leads us to propose potential targets for transmission blocking inter-ventions among some of the unique aspects of parasite sex. It also reveals unex-pected, conserved aspects of developmental regulation, sperm biogenesis and gamete fusion that may represent ancestral mechanisms present already close to the last eukaryotic common ancestor.