Type IV pili are major adhesins of many bacterial organisms. Adhesion by these structures is usually mediate by adhesin proteins located at the tip of a pilus than can extend a significant distance from the bacterial surface. The PilC proteins are proposed to be the major adhesins associated with the Type IV pili of Neisseria species and each strain encodes two of these proteins, PilC1 and PilC2. Surprisingly, these large (~110-kD) proteins are subject to high frequency ON/OFF switching due to polyC tracts present within the reading frames. These proteins exhibit divergence in central portions of the genes both within and between strains indicating that the ligands for these proteins may be divergent between the two proteins and between strains. An alternate view is that amino acid differences are driven by immune escape.
The overall aim of this project is to association structural differences in these proteins with functional differences. The project will combine comparative genomics, structural techniques and biological assays to test for associations between structure and function. Due to the large sizes of these proteins, it is proposed to utilise CRYO-EM to assess structural features and to look at interactions between the proteins and the Type IV pilus. The critical hypotheses are 1) that the PilC1 and PilC2 proteins have differing ligands due to differences in the ligand-binding pocket; 2) the PilC proteins exhibit antigenic variation in surface-exposed loops between strains; 3) phase variation enables switches in tissue tropism and immune escape.
Supervision will be provided by Prof Chris Bayliss, a specialist in the genomics of bacterial pathogens, and Prof Russell Wallis, a specialist in structural analyses of proteins.
We are looking for individuals who are interested in combining genetics and bioinformatics with structural analyses of proteins. Training will be provided to bridge gaps in each of these areas. We anticipate that this programme will produce a researcher who has the perfect combination of genetic and structural expertise for tackling the under-explored area of applying structure-function studies to utilised to infectious disease problems.
The Midlands Integrative Biosciences (Doctoral) Training Partnership (MIBTP) is a BBSRC funded doctoral training partnership between University of Warwick, University of Birmingham, University of Leicester, Aston University and Harper Adams University. The universities are separate entities, but there is large and growing cooperation between partners. We recognise that interdisciplinarity underpins most significant research and that critical mass is vital to ensure impact globally.
Entry requirements:
- Those who have a 1st or a 2.1 undergraduate degree in a relevant field are eligible.
- Evidence of quantitative training is required. For example, AS or A level Maths, IB Standard or Higher Maths, or university level maths/statistics course.
- Those who have a 2.2 and an additional Masters degree in a relevant field may be eligible.
- Those who have a 2.2 and at least three years post-graduate experience in a relevant field may be eligible.
- Those with degrees abroad (perhaps as well as postgraduate experience) may be eligible if their qualifications are deemed equivalent to any of the above.
For further information please contact [Email Address Removed]
Application advice:
To apply please refer the application instructions at
https://le.ac.uk/study/research-degrees/funded-opportunities/bbsrc-mibtp
You will need to apply for the PhD place at University of Leicester and also submit your online application notification to MIBTP. Links for both are on the above web page.
Project / Funding Enquiries: For further information please contact [Email Address Removed]
Application enquiries to [Email Address Removed]
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