Fully Funded PhD: Multifunctional Chemical Probes for Molecular Mapping of Cellular and Subcellular Protein Networks

Understanding the interactions between proteins and their neighbours within an unperturbed biological environment is a significant technical issue in drug discovery and fundamental disease research. Recent investigations into disease progression and patient variability have shown that in addition to accumulative genetic and epigenetic changes, variation and modulation of cellular protein networks plays a key role in the disease phenotype. Current methods developed to study these changes have significant limitations, especially in patient relevant material.

This project will create a first of its kind fully chemical spatiotemporal labelling technology to identify protein networks, without the need for genetic alteration. This novel approach will allow proteins to be studied in unperturbed patient samples and to map alterations to the subcellular networks upon disease progression and response to therapeutic intervention. This project will utilise established spatially targeting probe modalities developed by Prof. Watkinson along with novel protein labelling technologies recently developed in Dr Lewis and Dr Britten’s laboratories in a cross-disciplinary project involving chemical synthesis and chemical biology to develop a clinically accessible technology for proteomic analysis.

Project aims and objectives

The aim of this research is to develop novel chemical spatiotemporal labelling technology to identify protein networks within specific cellular organelles. Underpinning this aim are 4 objectives:

1. To undertake a critical literature review relating to cell organelle targeting fluorescent probes and the current limitations of protein labelling technology.
2. To undertake the design, synthesis and optimisation of the activation wavelength of small molecule fluorescent proximity probes.
3. To investigate the spatial control of protein labelling probes through chemical design and synthesis.
4. To investigate the spatiotemporal proximity labelling of the optimised probe toolbox in a range of cellular organelles.