Understanding how force is sensed in cells by the Piezo1 mechanosensitive channel

One full scholarship is available at the Leeds Institute of Cardiovascular and Metabolic Medicine. This scholarship is open to UK applicants and covers fees plus maintenance. This fully funded PhD place provides an exciting opportunity to pursue postgraduate research in the field of mechanosensitive ion channels.

<p>The ability of many organisms to sense mechanical forces generated e.g., by the heart is of vital importance for many of their functions e.g., control of blood pressure and respiration. For this reason, proteins that sense mechanical forces have an important role in human health. This project asks the fundamental question; how force is sensed by proteins found in the cell membrane. Despite some recent advances, it is still unknown how such proteins functions in diverse cellular environments and how they sense mechanical force.</p> <p>We recently showed that changes in the cytosolic region of a very important ion channel, the PIEZO1 ion channel is critical for its activation. In this project, we will use computational methodologies integrated with lab-bases studies to develop in-depth and molecular understanding of how PIEZO1 channel acts on mechanical force. In particular, the student will use molecular dynamics simulations to determine the conformational changes required within PIEZO1 channel for activation and how specific lipids regulate its activation. The models derived from the computer simulations will be evaluated/refined experimentally, using electrophysiology.</p> <p>The outcome of this study will reveal the activation mechanism of PIEZO1 in unparalleled molecular detail and it will show how the composition of the cell membrane has a regulatory effect in PIEZO1 function. Mutations on PIEZO1 have been shown to result in lymphatic dysplasia in humans, anemias, and potentially other abnormal conditions including heart failure. Therefore, understanding the function of PIEZO1 channel in molecular detail is critical as it can inform structure-based drug discovery for Piezo-related diseases.</p> <p>This position would suit a student with a biology, biochemistry, chemistry or physics background, or a combination of these. The student will be a part of a multidisciplinary team that already studies Piezo channels and has extensive experience on using advanced computational and lab-based approaches to study these channels.</p>

<p>To apply for this scholarship opportunity, applicants should complete an <a href="https://medicinehealth.leeds.ac.uk/faculty-graduate-school/doc/apply-2">online application form</a> and attach the following documentation to support your application. </p> <ul> <li>A full academic CV</li> <li>Degree certificate and transcripts of marks (or marks so far if still studying)</li> <li>Evidence that you meet the programme’s minimum English language requirements (if applicable)</li> </ul> <p>To help us identify that you are applying for this scholarship project please ensure you provide the following information on your application form;</p> <ul> <li>Select PhD in Medicine as your planned programme of study</li> <li>Give the full project title and name the supervisors listed in this advert</li> <li>For source of funding please state that you are applying for a LICAMM PhD Studentship</li> </ul> <p>If English is not your first language, you must provide evidence that you meet the University's minimum English language requirements (below).</p> <p><em>As an international research-intensive university, we welcome students from all walks of life and from across the world. We foster an inclusive environment where all can flourish and prosper, and we are proud of our strong commitment to student education. Across all Faculties we are dedicated to diversifying our community and we welcome the unique contributions that individuals can bring, and particularly encourage applications from, but not limited to Black, Asian, people who belong to a minority ethnic community, people who identify as LGBT+ and people with disabilities. Applicants will always be selected based on merit and ability.</em></p>

Applicants to this scholarship in the School of Medicine should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. A Master's degree is desirable but not essential.

The minimum English language entry requirement for postgraduate research study in the Faculty of Medicine and Health is an IELTS of 6.5 overall with at least 6.0 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid.

<p>We are offering 1 full-time PHD scholarship in the School of Medicine for one UK candidate, covering a maintenance grant matching UKRI maintenance stipend (£19,237 for 2024/25) and UK tuition fees for three years, subject to satisfactory progress. The award will be made for one year in the first instance and renewable for a further period of up to two years, subject to satisfactory academic progress.</p> <h6>Other Conditions</h6> <ul> <li> <p>Applicants must not have already been awarded or be currently studying for a doctoral degree</p> </li> <li> <p>Awards must be taken up by 1^st April 2025</p> </li> <li> <p>Applicants must live within a reasonable distance of the University of Leeds whilst in receipt of this scholarship</p> </li> </ul>

<p>For further information about the admissions process please contact the FMH PGR Admissions Team: <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a></p>