B Lloyd-Lewis

This fully funded PhD project at the University of Bristol, offered through the SWBio DTP, investigates the signalling mechanisms that regulate lysosomal membrane integrity and quality control. Lysosomes are vital organelles responsible for degrading cellular cargo and play key roles in nutrient sensing, growth signalling, and stress responses. Disruption of lysosomal membrane integrity can lead to the release of hydrolases, triggering cellular stress, inflammation, and cell death, and is implicated in diseases such as neurodegeneration and cancer. The project focuses on the role of Signal Transducer and Activator of Transcription 3 (STAT3) as a regulator of lysosomal function. STAT3 activation can induce lysosomal membrane permeability and programmed cell death (LM-PCD), but the underlying molecular mechanisms and the intersection with lysosomal quality control pathways like lysophagy remain unclear. The successful candidate will use multidisciplinary approaches, including advanced in vitro and in vivo models, fluorescence confocal and electron microscopy, biochemistry, proteomics, and computational biology, to explore how STAT3 signalling affects lysosomal membrane permeability and quality control. Project objectives include characterising lysosomes in STAT3 wild-type and knockout cells, exploring links between STAT3 signalling and lysophagy, and identifying changes to the lysosomal membrane during STAT3-induced LM-PCD. The project will provide training in a wide range of cutting-edge techniques and prepare the student for a career in academia or industry. The SWBio DTP supports students from diverse backgrounds and offers flexibility for those with caring responsibilities or other personal circumstances. The studentship is open to UK and international applicants, with up to 30% of places available for international students. Funding covers a four-year stipend (£20,780 for 2025/26), full tuition fees, research costs, and additional support for fieldwork, conferences, and placements. The application deadline is December 3, 2025. For more information and to apply, visit the SWBio DTP website or contact the project supervisor.