Investigating the conformational landscape of mechanosensitive ion channels by Molecular Dynamics, PELDOR and CryoEM

Membranes can sense mechanical forces, which is essential as it could indicate that they are about to burst due to high internal cell hydrostatic pressure. This is however avoided thanks to channel proteins such as mechanosensitive channels which can act as pressure relieve valves. Similar proteins are also important for the sensations of touch and proprioception in humans (Nobel Prize in Medicine/Physiology 2021). Yet our understanding of the mechanism of mechanosensation is lacking. How are mechanical forces, via lipid tethering, curve the membrane and pulling on the protein structure to open the channel? Can we lock this mechanism, using mutations or specific lipids, at various intermediate stages? We can follow it in “real time” using fast (ms-μs) techniques.

This project will utilize state-of-the-art Molecular dynamic simulations, PELDOR spectroscopy, and CryoEM to identify specific lipid and drug regulators for bacterial and human mechanosensitive channels. Overall, this will provide new information about the role of binding partners and physical membrane parameters in regulating mechanosensitive ion channel structure and function. Elucidation of the molecular mechanism of mechanosensation is an important step in the quest to develop drug-like molecules that target this essential process in bacteria and humans to tackle human disease.

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]