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 transmission 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 reorganised 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 new potential targets for transmission blocking interventions among some of the unique aspects of parasite sex. It also reveals unexpected, conserved aspects of developmental regulation, sperm biogenesis and gamete fusion that may represent ancestral mechanisms present already close to the last eukaryotic common ancestor.

Bio:
Having completed a PhD in parasitology at Imperial College London, Oliver Billker trained as a postdoc in bacterial pathogenesis at the Max-Planck-Institute for Infection Biology in Berlin. In 2002 he started his first lab at Imperial to study the cell biology of malaria parasites and their transmission by mosquitoes. His team later moved to the Wellcome Sanger Institute near Cambridge, UK, to develop genome scale genetic screening approaches in malaria parasites. In 2018 he joined Umeå University as Professor and was appointed Director of the Laboratory for Molecular Infection Medicine Sweden (MIMS), the Swedish node of the European Molecular Biology Laboratory, Europe’s intergovernmental flagship institute for the molecular life sciences. His research team now uses genomic approaches to investigate the sexual biology of malaria parasites and parasite-vector interactions, which is important to understand and eventually block the transmission of malaria by mosquitoes. Oliver Billker is a Wallenberg Scholar, EMBO Member and Fellow of the European Academy of Microbiology.