Defining the molecular mechanisms of A/B toxin attack and defense using single-molecule bioimaging

Protein toxins serve as weapons in evolutionary conflicts across biological systems. A number of toxins in the "A/B family" (e.g. tetanus, cholera, anthrax, shiga and diphtheria toxins) cause millions of deaths annually. An example is budding yeast K28 'killer' toxin which is a useful model of clinically relevant A/B toxins. However, the mechanisms of A/B toxin sensitivity and how cells defend against toxin is poorly understood. To investigate these mechanisms, you will develop novel single-molecule bioimaging tools using biophysics in the group of Mark Leake applied to yeast cell strains you will help develop in the MacDonald group which recently discovered the K28 defence factor, Ktd1 (Andreev et al., PNAS 2023). You will help to explore the hypothesis that endosomally localised Ktd1 works to sequester K28 toxin as it enters cells and directs toxin to the lysosome for degradation.