APICOLIPIDADAPT

Apicomplexa parasites are intracellular pathogens responsible for major human diseases such as malaria and toxoplasmosis. The absence of efficient vaccine, resistance and toxicity to existing treatments, all argue for the identification of new drug targets. 

Renewal of the therapeutic arsenal against Apicomplexa depends on deciphering the metabolic pathways that sustain parasite survival within the host and its physiological environment. Throughout their life cycle, Apicomplexa require large amount of nutrients, especially lipids for propagation and survival. We have recently uncovered that apicomplexan parasites and more particularly Toxoplasma parasites are capable of sensing and adapting to the fluctuating nutritional conditions provided by the human host. However, how the parasites orchestrate metabolic adaptation upon environmental changes in its host is currently unknown. 

To answer this we performed genome-wide CRISPR genetic screens in Toxoplasma gondii under changing host nutritional conditions, and identified the putative key players in these mechanisms: We have identified a central transcriptional regulator and key lipid effectors candidates, putatively fulfilling these essential functions. We aim to determine their function for nutrient acquisition and metabolic adaptation to host nutritional conditions using lipidomics, fluxomics, and transcriptomics approaches in Toxoplasma, during the acute and chronic phase of the disease.