Understanding how lysosomal regulation confers resistance to yeast killer toxin

FUNDING: 10 weeks (full time, 37 hrs per week, £12 per hour, £450 consumables, McQueen-Mason studentship funding)
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Dr. Amy Milburn, Biology, York

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A/B toxins (e.g. from tetanus, cholera, and diphtheria) are responsible for millions of deaths annually. However, the mechanisms of toxin sensitivity and how cells defend against toxin is poorly understood. The budding yeast A/B toxin, K28 ‘killer’ toxin, inhibits growth of susceptible yeast strains. K28 shows many similarities to clinically relevant A/B toxins. The MacDonald group recently discovered the K28 defence factor, Ktd1, which is required for toxin resistance. However, there is currently no mechanistic understanding of Ktd1 function. K28 toxin sensitivity is typically measured using a low sensitivity lawn-based growth assay. We have recently developed a highly sensitive 96-well plate assay and used it to implicate lysosomal genes in toxin resistance. The student will screen a library of relevant lysosomal deletion mutants for K28 toxin sensitivity, using our high-throughput assay and then ascertain trafficking and localisation of GFP-tagged Ktd1 in mutants with altered K28 sensitivity using super-resolution microscopy. The student will be trained in relevant assays and in bioinformatic tools to visualise and organise data and begin mechanistic dissection of any identified factors. Students will be expected to present their findings orally at a research day in York in September 2024.