Functional characterization of a novel peptidoglycan binding domain conserved in Gram-positive nosocomial pathogens

This project will represent a fantastic opportunity for a PhD student to have training across several disciplines including molecular biology, biochemistry, biophysics, structural biology and cell biology. It will also embrace state-of-the-art super resolution microscopy technologies developed at the University of Sheffield. The novel fluorescent probes developed in the context of this work will enable to explore peptidoglycan topology, a question that has remained intractable so far. Combined with the latest single-molecule imaging technologies available at the university of Sheffield, this work is therefore expecting to push the boundaries of scientific discovery and lead to major breakthrough in the field.
The PhD student will benefit from a stimulating interdisciplinary expertise provided by two supervisors from different disciplines (S. Mesnage is a microbial geneticist with strong background in cell wall biochemistry; M. Williamson is a biophysicist expert in protein structure). The successful candidate will be trained in several complementary approaches: (i) molecular biology and biochemistry for protein engineering; (ii) HPLC and mass spectrometry for bacterial cell wall analysis; (iii) Surface Plasmon Resonance, microcalorimety (Differential Scanning Calorimetry and Isothermal Titration Calorimetry) and NMR for protein-PG interactions, and (iv) super-resolution fluorescence microscopy to study the subcellular localization of proteins.
The training of the PhD student will also involve a close interaction with the team of Dr Simon Jones (department of Chemistry, University of Sheffield), who is currently developing synthetic schemes to produce peptidoglycan fragments.