How can we measure the fleeting molecular neighbourhoods that control signalling inside living cells?
Proximity-labelling methods provide a powerful way to address this problem by converting spatial proximity into a permanent chemical tag that can subsequently be detected by imaging or proteomics. However, current approaches face an important trade-off: the reactive chemistry needed to generate a measurable signal can perturb sensitive biological systems, while the spatial reach of labelling is difficult to control. This project will develop a new generation of chemically engineered proximity probes that act as tuneable molecular sensors of local cellular environments.
The student will design and synthesise new probe molecules whose chemical and physical properties are systematically varied to control their behaviour during proximity labelling. Combining synthetic chemistry with biochemical and cellular experiments, the project will establish how molecular structure determines key sensing properties including labelling efficiency, biological compatibility and spatial precision. Preliminary work from the supervisory team supports the feasibility of this concept while leaving substantial scope for fundamental discovery and technology development.
The project will progress through three linked stages. First, the student will create and characterise a focused library of new proximity-labelling probes and establish relationships between chemical structure and probe behaviour. Second, promising probes will be evaluated in living cells using biochemical assays, advanced fluorescence imaging and super-resolution microscopy to determine how accurately and efficiently they report local molecular neighbourhoods. Finally, selected probes will be applied to biologically challenging systems in which conventional proximity labelling can itself perturb the processes being studied. Proteomic analysis will be used selectively to identify the molecular networks revealed by the new sensing platform.
This PhD lies at the interface of chemistry and biomedical science and will be jointly supervised across complementary research environments. The student will receive broad training spanning synthetic organic chemistry, chemical biology, cell culture, biochemistry, quantitative imaging, proteomics and data analysis, with opportunities to work across both laboratories and specialist research facilities. The supervisory team has an established record of collaboration and co-supervision at the chemistry-biology interface, providing an integrated environment in which the student can develop genuine interdisciplinary independence.
The long-term goal is to establish chemical design principles that allow proximity-labelling probes to be matched to the biological question being asked. By making probe chemistry a controllable sensing parameter, this project aims to expand the range of molecular environments that can be studied in living cells and provide new tools for understanding dynamic cellular organisation in health and disease.
This project is expected to start in September 2027.
Before you apply: You should contact the project supervisors to learn more about the project and discuss whether it may be suitable for you.
How to apply:
To be considered for this project, you must submit a formal application through our online application portal. If you already have an applicant account, use this link to open an application for FSE PhD President's Doctoral Scholarship. If you do not yet have an applicant account, follow the account setup instructions. Once your account is set up, use this link to open an application for this programme.
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: Applicants are expected to hold (or be about to obtain) a minimum upper second-class undergraduate honours degree (or equivalent) in Chemistry, Pharmacy or related areas. Research experience in organic synthesis and/or cell biology is desirable.
FSE_PDS
Funding Notes
Funding covers tuition fees, an annual stipend at the UKRI minimum rate (currently £21,805 per year) plus £1,000/annum enhancement, and a research training support grant of up to £20,000 for the full 4-year programme.
