During their life cycle, malaria parasites enter different milieus in both the vertebrate host and the mosquito vector. Parasites have to adapt to these changing conditions and it is therefore not surprising that they have evolved strategies to link developmental decisions to signals in their environment. This also holds true for the intra-erythrocytic stages of the parasites: While the red blood cell provides parasites with essential nutrients and shields the intruder from host immune responses, the intra-erythrocytic localisation seemingly isolates P. falciparum from the outside world. Despite this spatial separation, parasites are able to sense external signals, including the host-derived serum lipid lysophosphatidylcholine (lysoPC). Intriguingly, parasites are able to induce specific transcriptional programmes in response to changing lysoPC concentrations. This allows parasites to control essential processes, including growth, metabolism, cell cycle exit and the production of transmission stages in an adaptive manner. The apparent lack of canonical nutrient-sensing pathways in Plasmodium species, however, raises questions about how parasites are able to perceive nutritional stimuli and how these environmental signals are translated into appropriate downstream responses.
It is the aim of this project to identify and functionally characterise the molecular players involved in environmental sensing of malaria parasites. We are combining our expertise in P. falciparum cell culture with diverse reverse genetics approaches and phenotypic readouts to reach this aim.