Academic Research

Building upon the identification of promising hit compounds from a cellular screen, this project aims to characterize their mechanistic action and downstream consequences on sphingolipid biology in Toxoplasma gondii.
Initial hits, which disrupt parasite growth and sphingolipid homeostasis without host cell toxicity, provide a crucial starting point for validating the sphingolipid biosynthesis and transport pathway as druggable target(s).

The first objective is to determine the precise enzymatic targets of these candidates. We will enrich key parasite enzymes, including serine palmitoyltransferase and ceramide synthase, from recombinant parasite lysates. Using fluorescently-tagged substrates, we will conduct in vitro enzyme assays to quantify the inhibitory efficacy and potency (IC50) of each hit.
Subsequently, we will investigate the functional repercussions of inhibition on intracellular lipid synthesis and trafficking. We hypothesize that depleting sphingolipid pools or transport disrupts critical organelles. We will establish a Bioluminescence Resonance Energy Transfer (BRET) system to monitor lipid-protein interactions.

Briefly, this project will delineate the molecular targets of novel anti-Toxoplasma compounds and illuminate the disruptions in lipid dynamics. 

Ph.D. students

The project is suitable for a doctoral scholar with experience in molecular parasitology, cell biology, and biochemistry.