Scott Landfear

The Landfear laboratory studies the biological functions of membrane transport proteins in parasitic protozoa including Leishmania, African trypanosomes, and malaria.  Because these parasites live within either mammalian or insect hosts during their entire life cycles, they are dependent upon uptake of a plethora of essential nutrients from their hosts for survival.  Uptake is mediated by integral membrane proteins designated transporters, carriers, or permeases.  Our research focuses on transporters that play especially important roles in the life cycles of these parasites, particularly in the infectious stages.  These studies employ a synthesis of molecular biology, biochemistry, genetics, cell biology, and pharmacology. 

Transporters for the sugar glucose play important roles in the biochemistry of many cells, since glucose is a key nutrient for both energy and biosynthesis.  The glucose transporters of Leishmania, trypanosomes, and malaria are essential for life in the mammalian host.  We have identified 3 distinct glucose transporter isoforms in Leishmania and studied their different functions and subcellular locations.  Deletion of the 3 glucose transporter genes is lethal to the infectious stage of the life cycle but not to the stage that lives within the insect vector, and we are determining why glucose uptake is essential for the infectious stage.  We are also developing a high throughput screen to identify small molecule inhibitors of Leishmania, trypanosome, and malaria glucose transporters that could represent leads for development of anti-parasitic drugs.

Purines are also essential nutrients that parasites need to salvage from their hosts.  We are studying purine transporters in Leishmania and trypanosomes and attempting to determine which of these transporters are essential for parasite viability.  Current evidence suggests that one of the purine transporters may be specialized to function in the infectious stage of the Leishmania parasite that lives inside host macrophages and that one of the trypanosome transporters may localize to intracellular membranes of the parasite rather than to its surface membrane. 

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