Dissecting the emergence of complexity in living bacteria, one molecule at a time

Studying the emergence of complexity in living cells is challenging. Bacterial sporulation however, presents a fantastic model system for doing so. Using exciting state-of-the-art microscopy and genetics techniques we can now follow the emergence of cellular complexity one molecule at a time as it actually happens in living cells. To survive starvation and/or stress, bacteria such as Bacillus and Clostridia abandon growth and follow a pathway of cell differentiation to form a metabolically dormant spore. These spores are resistant to heat, chemical stresses and antibiotic treatment and, as a result, spores of pathogens such as B. cereus and C. difficile are associated with food poisoning and hospital acquired infection respectively. Sporulation begins when the rod-shaped bacterial cell divides asymmetrically giving rise to genetically identical daughter cells with different fates. Different sets of genes are expressed in the larger mother cell and the smaller forespore. The mother cell then engulfs the forespore, and in the nurturing environment of the mother cell cytoplasm, protein layers are deposited around the forespore as it matures into a resistant spore. Finally, in an act of sacrifice, the mother cell lyses releasing the mature spore which can survive indefinitely and germinate when favourable conditions for growth are restored.

Spore formation presents a treasure trove in molecular cell biology featuring starvation sensing and signal integration, polar cell division, differential gene expression, phagocytosis and programmed cell death. For many years, AJW has been investigating structure-function relationships in these proteins using techniques of protein biochemistry and crystallography and the student will gain exposure to, and training in, these techniques. The central and distinct focus, here, will be the determination of structures of complexes in live sporulating cells. Using advanced microscopes designed and built in the laboratory of MCL, the student will observe individual complexes in living bacterial cells and determine their composition and stoichiometry as well as the dynamics of their assembly and disassembly. In order to carry out these studies, the student will use genetic engineering methods to generate strains expressing target proteins fused to fluorescent reporter proteins. Specifically, we are interested in (i) a protein phosphatase that activates compartment specific gene expression in the forepore (ii) complexes of membrane proteins that facilitate the movement of the mother cell membrane around the forespore membrane during cell engulfment and (iii) a protein that mediates the fusion of the engulfing membranes at the completion of engulfment.

Shortlisting will take place as soon as possible after the closing date and successful applicants will be notified promptly. Shortlisted applicants will be invited for an interview to take place at the University of York on Friday 12 May. Candidates will be asked to give a short presentation prior to their interview by an academic panel. All research students follow our innovative Doctoral Training in Chemistry (iDTC): cohort-based training to support the development of scientific, transferable and employability skills

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