Immune cells continuously patrol the body to maintain health. Central to this process is their ability to sense environmental cues and respond appropriately. When T cells engage antigen-presenting cells (APCs), they simultaneously encounter numerous stimulatory, co-stimulatory, inhibitory, and adhesive signals at specialised contact sites known as immune synapses. Growing evidence suggests that the nanoscale spatial organisation of these molecular cues plays a critical role in determining how T cells interpret and integrate information.
The nanoscale architecture of the immune synapse, including how receptors and their ligands cluster, segregate, and reorganise in space and time, varies substantially depending on the combination of signals present. Because signalling output appears to depend as much on this spatial organisation as on ligand identity itself, the same receptor may generate distinct downstream responses depending on the nanoscale context in which it is engaged. Understanding immune signalling therefore requires not only identifying the molecular components involved but also determining how these components are wired into functional signalling circuits.
This project will directly address this challenge by combining a synthetic antigen-presenting cell platform with state-of-the-art nanoscale molecular mapping technologies. Engineered APCs displaying bioorthogonal click-biology handles will be used to present precisely defined combinations of peptide-MHC complexes, co-stimulatory receptors, co-inhibitory receptors, and integrin ligands at controlled surface densities. These programmable cells will provide an unprecedented ability to manipulate the composition and organisation of immune synapses. Using a combination of super-resolution imaging and photocatalytic proximity-labelling approaches, the student will generate detailed molecular maps of synapse architecture and determine how distinct combinations of extracellular cues are translated into intracellular signalling outcomes.
The project consists of three integrated objectives. First, the student will establish and validate the synthetic APC platform, optimising ligand display and benchmarking super-resolution photocatalytic proximity-labelling methods. Second, they will apply these technologies to generate time-, distance-, and ligand-resolved maps of immune synapse organisation. Finally, biochemical and functional assays will be used to determine how specific synaptic architectures influence downstream signalling pathways and T-cell activation.
The student will receive multidisciplinary training spanning chemical biology, immunology, advanced microscopy, proteomics, and quantitative data analysis. Supervision from world-leading institutes across the School of Natural Sciences and the Lydia Becker Institute of Immunology and Inflammation will provide expertise within chemistry, cell biology/biochemistry and immunology, creating a highly interdisciplinary training environment, while benefiting from the University's broader postgraduate researcher training programmes and cross-faculty research networks.
Beyond advancing our fundamental understanding of immune-cell communication, this work has significant translational potential. The findings will inform the rational design of synthetic APCs for cellular therapies and guide the selection of co-stimulatory and checkpoint-ligand combinations in CAR-T and other immunotherapies. By establishing how ligand composition shapes immune synapse architecture and function, this project will help transform immune engineering from an empirical process into a mechanism-guided design discipline.
This project is expected to start in September 2027.
https://aarontrowbridge1.wixsite.com/trowbridgegroup
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 Biochemistry or Chemistry. Research experience in Chemical Biology is desirable.
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.
