Understanding the molecular mechanisms of periplasmic chaperones to underpin the discovery of novel antimicrobial targets in gram-negative pathogens

Antibiotic resistance is projected to cause 10 million deaths per year by 2050, with gram-negative pathogens comprising 9 of the 12 bacteria that pose the greatest threat (World Health Organisation). The outer membrane (OM) of gram-negative bacteria is essential for bacterial growth and virulence and is an ideal, but underexplored, target for next-generation antimicrobials. 

OM proteins (OMPs) are essential components of the OM. OMPs are synthesised in the cytoplasm and bound by chaperones to protect them from aggregation before reaching the OM. Perturbing OMP:chaperone interactions reduces viability/virulence and induces cell stress responses. This makes OMP:chaperone interactions excellent potential targets for antibacterial molecules.

 Here we will uncover how OMPs bind the chaperone SurA and determine if small-molecules that bind SurA interfere with its function and reduce virulence/viability. We will exploit state-of-the-art structural mass spectrometry and proteomics, single molecule Förster resonance energy transfer (smFRET), and molecular biology techniques to elucidate the molecular mechanism of OMP recognition by SurA. Further, we will identify molecules that bind OMP recognition sites on SurA, and test their ability to restrict cell growth. The outcomes will be a new fundamental understanding of chaperone:client interactions and the identification of novel strategies that may combat multi-drug resistant bacterial infections.

Eligibility: 

You should hold a first degree equivalent to at least a UK upper-second class honours degree or a MSc degree in a relevant subject.

Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The Faculty of Biological Sciences minimum requirements in IELTS and TOEFL tests are:

• British Council IELTS - score of 6.0 overall, with no element less than 5.5
• TOEFL iBT - overall score of 87 with the listening and reading element no less than 20, writing element no less than 21 and the speaking element no less than 22.

How to apply:

To apply for this project applicants should complete an online application form and attach the following documentation to support their application. 

• a full academic CV
• degree certificate and transcripts of marks
• Evidence that you meet the University's minimum English language requirements (if applicable).

To help us identify that you are applying for this studentship please ensure you provide the following information on your application form;

• Select PhD in Biological Sciences as your programme of study
• When asked for source of funding please make it clear that you are applying for a "White Rose BBSRC DTP Studentship"
• Give the full project title and name the supervisors listed in this advert. You can be considered for up to 3 projects in total.

If you have any further queries regarding this opportunity, please contact [Email Address Removed]