(BBSRC NWD) Cells on a leash: using bio-electrochemistry to pull on a [2]rotaxane thread

Communication across cell membranes is a crucial function that allows cells to respond to chemical messages in their external environment. These chemical messages bind to the exterior of proteins (receptors) that both span the membrane and have interior regions projecting into the cell. Binding causes these receptors to change shape along their length, with changes in the interior regions telling the cell to change its behaviour. This process is called “signal transduction”; sending information across membranes without physically transporting any substance through them. 

We aim to develop entirely new types of signal transduction that will allow cellular control using unnatural signals.[1],[2] This project will specifically focus on [2]rotaxane-based synthetic receptors able to make cells externally controllable by electro-mechanical stimuli. [2]Rotaxanes are interlocked molecules with a long molecular “thread” that passes through the centre of a molecular “ring”. In our design, the ring is fixed in the membrane centre, with the thread spanning the membrane from outside to inside. A unique bio-electrochemistry platform, the Electrochemical Leaf, will be used to “pull” on the external end of the thread and move it further away the membrane. The concomitant decrease in the length of thread projecting into the interior will lead to a measurable change in fluorescence. This pulling of the thread through the membrane will also cause a metal ion, which is attached to the interior end of the thread, to be displaced and released inside the cell. This metal ion will act as an internal message for the cell’s molecular machinery, leading to a measurable change in cellular behaviour. 

A key outcome from this project will be proof-of-concept: showing a molecular thread can move through a molecular ring embedded in the membranes of living cells. Furthermore, should this movement alter cell behaviour, it would be the first example of synthetic signal transduction in a living cell caused by motion of an artificial molecular device. 

The project will involve the chemical synthesis of [2]rotaxanes and analysis of their behaviour in different environments. They will then be interfaced with the Electrochemical Leaf and the ability of electrochemical inputs to cause thread motion will be assessed. After studying thread motion in liposomes, each [2]rotaxane system will be investigated in mouse cell membranes. 

Eligibility

Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science, engineering or technology. 

International applicants

We are only able to offer a limited number of full studentships to applicants outside the UK. Therefore, full studentships will only be awarded to exceptional quality international candidates due to the competitive nature of this scheme.

International applicants must ensure they meet the academic eligibility criteria (including English language) before applying. Visit our ‘Eligibility and entry requirements’ page to find out more about our English language requirements.

Before you Apply

Browse our BBSRC NWD in Bioscience projects and discover one you’re passionate about that matches your interests, ambitions and goals.

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

How to Apply

All applications should be made via our specific BBSRC NWDP in Bioscience online application form. This is a separate application process specifically for all candidates for this scheme. Applications should not be made through either university’s usual online application system.

You must submit your application form along with the required supporting documents by the deadline date. You can select up to two projects on one single application, noting the title of each project from the advert and the supervisor name. This can include two projects from one institution or a project from each institution. 

Before you complete your application you should prepare the following supporting documents:

·      CV

·      Personal statement

·      Degree certificates and transcripts (if your qualification is still pending, please ensure this is clear on your application form and you can send this to us at a later date)

·      Two references

·      Evidence of English language qualifications (if completed)

Complete the application form: https://forms.office.com/e/HVXALrVa0P

Once you have completed your application, you’ll receive a confirmation email and             you should reply to this email with all of your supporting documentation as soon as possible to: nwd-bbsrc.applications@manchester.ac.uk

Deadline: Friday, 31 January 2025, 5pm

Late or incomplete applications will not be considered.

If you need help with this stage of the process, or have any queries regarding your eligibility (such as if you achieved unexpectedly low degree results due to extenuating circumstances), please contact the Doctoral Admissions team for advice at fbmh.doctoralacademy.admissions@manchester.ac.uk.

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Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website.