Prostate cancer is the second most diagnosed cancer in men worldwide and remains a major cause of cancer mortality. Loss of BRCA2, a protein essential for DNA repair, is associated with aggressive disease and can confer sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. Although genomic testing can identify BRCA2 alterations, there is currently no reliable antibody-based method for detecting functional BRCA2 protein loss in tumour tissue. This limits spatial analysis of BRCA2 expression and does not enable selecting patients for precision treatment. This project will develop molecularly imprinted polymer nanoparticles (nanoMIPs) as stable, reproducible synthetic alternatives to antibodies for sensing BRCA2 loss in prostate cancer tissue.
The objectives are to: (1) generate high-affinity nanoMIPs against defined BRCA2 regions; (2) develop labelled nanoMIP systems for detecting BRCA2 in protein and cell-based assays; and (3) establish and validate a tissue-based assay that distinguishes BRCA2-mutant from wild-type prostate cancers.
The student will use computational peptide-structure prediction and molecular docking to guide monomer selection before producing nanoMIPs by solid-phase synthesis. Nanoparticle size, morphology and chemistry will be evaluated using dynamic light scattering, electron microscopy and infrared spectroscopy. Binding affinity and selectivity will be measured using surface plasmon resonance and isothermal titration calorimetry. Lead materials will be functionalised with biotin or fluorescent reporters and assessed using Western blotting, flow cytometry, confocal microscopy and BRCA2-knockdown cell models. Finally, the student will optimise an immunohistochemistry-compatible workflow and evaluate lead nanoMIPs using molecularly characterised BRCA2-mutant and wild-type prostate cancer tissues from the Manchester Cancer Research Centre Biobank, benchmarking assay performance against genomic status.
Anticipated outcomes include a validated prototype assay for functional BRCA2 deficiency, new understanding of how epitope selection and polymer composition affect recognition of a large, structurally complex protein, and a translational dataset supporting further clinical and commercial development. The approach will ultimately improve patient stratification for PARP inhibitor treatment and link protein expression to patient outcome.
This cross-faculty project integrates materials engineering and computational modelling in the Faculty of Science and Engineering with cancer biology, genomics, pathology and clinical expertise in the Faculty of Biology, Medicine and Health. Professor Peeters will lead training in nanoMIP design, characterisation and translation; Dr Dawson will assist with development of computational workflows; Professor Bristow will provide expertise in BRCA2 biology and genomics; and Mr Sachdeva will contribute clinical prostate cancer, patient input and PARP-inhibitor trial expertise. Dr Pankaj Singla (Peeters group) and Claire Hart (Sachdeva/Bristow group) will provide day-to-day laboratory support. Structured placements across the four research environments, regular joint supervision, group meetings, journal clubs and Manchester-wide researcher-development programmes will create an integrated PGR training environment. The student will also receive training in experimental design, statistics, research governance, scientific communication, patient involvement (via the Christie Hospital) and responsible innovation.
The project directly advances the Sensing the World theme by connecting biological recognition and physical sensing with quantitative interpretation and clinical decision-making. It establishes a new way of working across faculties to address a complex global health challenge while training a doctoral researcher to translate discoveries between engineering and clinical practice.
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 Chemical Engineering, Bioengineering, Biology or Chemistry. Research experience in polymer science, cancer biology or biosensing 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.
