[School of Natural Sciences PhD Scholarships] Sending a message down a golden thread

About the project

About the Project Background: Transmembrane receptors in cell membranes, like G-protein coupled receptors (GPCRs), relay chemical messages into cells in a process called “signal transduction”. With approx. 35% of approved drugs targeting GPCRs,[1] understanding how these important proteins function is a key goal for biomimetic chemistry. Furthermore, engineering synthetic molecules that can mimic GPCRs could make cells externally controllable using unnatural stimuli; “short-circuiting” natural signalling pathways. Aims: This multidisciplinary PhD project, which links organic chemistry to biology, will develop synthetic molecules able to transmit signals across phospholipid bilayers.[2] These signals will switch gold(I)-catalysed reactions on or off. The synthetic molecules (receptors) will comprise a gold(I) complex attached to a [2]pseudorotaxane core, a structural motif that has a molecular “thread” passing through a molecular “ring”. After insertion of the [2]pseudorotaxane receptors into bilayer membranes, enzymatic modification of the exterior part of each [2]pseudorotaxane receptor will move the thread through the ring. This motion will in turn either activate or deactivate the gold(I) catalyst, which is located on the other side of the membrane. Approach: The project will build on ongoing work. It will start with the chemical synthesis of catalytically active [2]pseudorotaxanes and control compounds. The ability of supramolecular interactions and catalysis to initiate motion in prototype [2]pseudorotaxane systems will be quantified in organic solvents, with this knowledge used to understand analogous behaviour in cell mimics (vesicles). Initially the production of fluorescent products in solution and inside vesicles will be measured. Then the best performing systems will be studied in the membranes of living cells, with external stimuli switching on/off the catalytic production of messenger molecules. Outcomes: A key outcome would be the first example in cells of molecular thread motion through a molecular ring. Furthermore, should this movement alter cell behaviour, cells will have been made externally controllable using unnatural chemical stimuli. Receiving, communicating, and transforming molecular information into a catalytic output will be an underpinning technology for molecular robotics. The candidate: This project would suit an applicant with core knowledge/skills in chemical synthesis and supramolecular chemistry. An understanding of how to analyse catalytic reactions is desirable. An interest in biological systems will be needed, although no prior experience of cell culture techniques is required. This project is expected to start in September 2027. Before you apply: We strongly recommend that you contact the supervisors for this project before you apply. How to apply: To be considered for this project you must complete a formal application through our online application portal. If you already have an applicant account this link will directly open an application for PhD School of Natural Sciences Scholarships . If you don’t already have an applicant account, please follow the instructions here . When applying, please specify the full title and supervisor/s of the project, details of your previous study, and names and contact details of two referees. You must also upload a Supporting Statement describing your motivation to apply to the project, your CV and transcripts of awarded and in-progress university qualifications . Please note late or incomplete applications will not be considered. Equality, diversity and inclusion are fundamental to the success of The University of Manchester and central to all our activities. A diverse research community strengthens creativity, productivity and quality, while increasing the societal and economic impact of our work. We welcome applicants from all career paths, backgrounds and sections of the community, regardless of age, disability, ethnicity, gender, gender expression, sexual orientation or transgender status. We welcome applications from candidates returning to study after a career break or experience in other roles. Flexible study arrangements may be available, including part-time study at 50%, 60% or 80%, subject to the requirements of the project and funder. Eligibility: The standard academic entry requirement for this PhD is an upper second-class (2:1) honours degree (or international equivalent) in Chemistry OR any upper-second class (2:1) honours degree and a Master’s degree at merit (or international equivalent) in Chemistry. Previous research experience in supramolecular chemistry, cell culture and/or organic synthesis is desirable. This project will remain open until filled. If your application is submitted by 1 st November 2026, you can expect a decision by 18 th December 2026. If your application is submitted by 15 th January 2027, you can expect a decision by 30 th March 2027. Self or externally funded students can also be considered for this project. FSESoNS

Research areas