PhD: Molecular mechanisms modulating host epithelial integrity in response to bacterial adhesion

Bacterial adhesion is one of the first and most crucial steps during the interaction between bacteria and host organisms. This makes it an exciting topic to investigate in the context of infectious disease, and a potential target of novel drugs targeting bacterial virulence.
We recently identified Multivalent Adhesion Molecules (MAMs) as a new and wide-spread family of bacterial adhesins mediating host-pathogen interactions (Krachler et al, PNAS 2011). We are developing novel anti-infectives, which are bacteriomimetic materials based on MAMs, to competitively inhibit pathogen attachment and thus attenuate infections. We discovered that the multivalent binding of Vibrio parahaemolyticus MAM to the host lipid phosphatidic acid leads to activation of the small GTPase RhoA and actin rearrangements, resulting in enhanced paracellular permeability of intestinal epithelium (Lim et al, PLOS Pathog 2014). We hypothesize that MAMs found in commensals differ in their ability to bind host lipids, and thus in the way they affect host signaling.

Using a range of state-of-the-art molecular techniques, including protein and lipid biochemistry, microbial genetics, infection models and high resolution imaging, this project will study how pathogens and commensals use MAMs to interact with their host, and how these signals are integrated in a polymicrobial community. These findings will be directly applied to engineer adhesion inhibition materials with improved efficacy, while avoiding side-effects.

If you are a highly motivated individual and keen to work with us, we look forward to hearing from you. An excellent first degree is essential, and should ideally be in life sciences although we are interested from anyone who thinks they could make a valuable contribution to our work. To learn more details about our research and to discuss the direction of potential projects, please contact Dr Anne Marie Krachler (a.krachler@bham.ac.uk) and include your current CV and a brief statement of your research interests

The School of Biosciences offers a number of UK Research Council (e.g. BBSRC, NERC) PhD studentships each year. Fully funded research council studentships are normally only available to UK nationals (or EU nationals resident in the UK) but part-funded studentships may be available to EU applicants resident outside of the UK. The deadline for applications for research council studentships is 31 January each year.

Each year we also have a number of fully funded Darwin Trust Scholarships. These are provided by the Darwin Trust of Edinburgh and are for non-UK students wishing to undertake a PhD in the general area of Molecular Microbiology. The deadline for this scheme is also 31 January each year.
 

Funding Notes

All applicants should indicate in their applications how they intend to fund their studies. We have a thriving community of international PhD students and encourage applications at any time from students able to find their own funding or who wish to apply for their own funding (e.g. Commonwealth Scholarship, Islamic Development Bank).

The postgraduate funding database provides further information on funding opportunities available http://www.birmingham.ac.uk/postgraduate/funding/FundingFilter.aspx and further information is also available on the School of Biosciences website http://www.birmingham.ac.uk/schools/biosciences/courses/postgraduate/phd.aspx