Precise Nanomedicines guided by Super-Resolution Imaging

T-cells are essential for human immunity, playing a central role in pathogen elimination and tumour surveillance. When they recognise a toxic substance, via the receptors on their surface, a cascade of chemical reactions instructs the cells on how to behave. T cells rely on several factors to shape immune responses, including ligand-receptor affinity, on- and off-rates of the interaction and number and local density of receptors expressed on the cell surface. Outstanding questions remain on how these mechanisms work, and on how researchers can harness this knowledge to engineer effective nanomaterials that can re-direct T cells towards disease causing cells.

During this project the candidate will leverage the capabilities of highly multiplexed (tens of targets), ultra-resolved (<5 nm) and quantitative (integer counting of molecules) 3D fluorescence imaging to provide positive feedback for the design of nanomaterials for T cell-based immunotherapies.

This project comprises three major interwoven efforts: (1) Identify the functionally relevant spatial organisation of key cell surface proteins implicated in T cell immunotherapies down to the single-protein level; (2) Develop tools to quantitatively characterise in 3D the molecular distribution of functional groups on the surface of nanomaterials; (3) Fabricate novel patterned nanomaterials designed to maximise the spatial presentation of ligands to T cell surface proteins and visualise ligand-receptor interactions.

The project will be carried out jointly between Dr. Sabrina Simoncelli's and Prof. Giuseppe Battaglia's labs and it involves cross-disciplinary work including advanced optical microscopy (using start-of-the-art 3D super-resolution imaging techniques) and chemical (synthesis of nanomaterials) and computational approaches (including advanced image analysis using machine learning).

In terms of the EPSRC strategy and portfolio the proposal aligns well with current EPSRC themes of Healthcare Technologies and Physical Sciences. Furthermore, the scientific goals of this project are in line with the ambitions laid out by EPSRC within Productive Nation Outcome P1 and Healthy Nation Outcome H4: Develop future therapeutic technologies.