Authors

K Spence²; N J Bryant¹; P B Walrad²;  ¹ University of York, UK;  ² University of York, Centre for Immunology and Infection, UK

Discussion

Autophagy is an important degradation system by which cells recycle unwanted or damaged cytoplasmic material. During times of stress and cellular differentiation this process is upregulated. Macroautophagy (the main autophagy pathway) begins with formation of a phagophore, a double membranous structure, that expands to engulf cellular components, becoming an autophagosome. This autophagosome then fuses with the lysosome to deliver its contents for degradation and subsequent recycling.

Many of the pathways and components involved in autophagy and membrane fusion events are highly conserved in eukaryotic organisms. Observations in yeast and mammalian systems could therefore provide insight into the roles and mechanisms of related proteins found in the medically-important Leishmania parasite.

Research will characterise the interactions of the Tlg2 t-SNARE protein and its partner SM protein Vps45 in Leishmania spp. and determine whether, as is observed in yeast, they play a role in autophagy. Autophagy has previously been shown to be critical for Leishmania differentiation into human-infectious forms. A better understanding of the molecular mechanisms underlying these processes could potentially prime development of therapeutic strategies to combat leishmaniasis.

Preliminary evidence from genetic experiments examining phenotypic outcomes relevant to lifecycle progression and infectivity of the parasites will be presented. Functional homology experiments will examine whether Leishmania-derived Tlg2 can rescue tlg2Δ mutant yeast and demonstrate conservation of autophagic pathways