Antibody-drug conjugates (ADCs) offer a powerful strategy for the cell-selective delivery of therapeutics. Despite this approach used primarily in oncology applications, off target toxicity associated with delivery of cytotoxic payloads to non-cancerous cells and tissues is a current limitation with existing ADC designs. Whilst a number of factors can influence off target toxicity, ranging from antigen-antibody binding affinity, cell uptake mechanisms as well as the rate of release of the corresponding payload, understanding how to optimise designs to reduce systemic toxicity is vital. 

Project objective

This goal of this PhD project is to understand how the attachment chemistry (or warhead, W), linker groups (L) and drug payload (P), termed WLPs, influences cell surface target engagement, uptake and drug release as part of an ADC. You will develop synthetic routes to selectively attach WLPs to antibodies. This will be achieved by establishing a synthetic workflow to prepare ADCs which modulate the number of cytotoxic payloads as well as the type of linkers used to connect the antibody and payload.

You will then explore how these new ADC designs influences cell recognition, uptake and drug release. This will be achieved using cutting edge instrumentation based at Strathclyde. A Bruker Biosensors helix-cyto instrument will be used to explore how the binding kinetics of antigen-antibody interactions influence binding and subsequent uptake in target versus off-target cell lines, whereas in-cell NMR spectroscopy will define uptake properties of these ADCs. Collectively, this studentship will traverse synthetic chemistry, biophysical analysis and biological evaluation next-generation ADCs over the 3.5 year programme of research.

Academic environment

This project is a joint interdisciplinary collaboration between the Burley and Chamberlain laboratories situated within Pure and Applied Chemistry (PAC) and the Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), and industrial supervision from Dr Matthew Gray (GSK).

This project is ideally suited if you have a keen interest to apply your synthetic chemistry skills across the chemistry-biology interface aided cutting-edge bioanalytical tools. You are expected to possess at least an upper second-class degree (or equivalent) in Chemistry or Biochemistry backgrounds. You will receive training on a wide range of technical skills including and not limited to solution and solid phase synthesis, cell culture, cell and molecular biology, and in-cell NMR techniques all based within the University of Strathclyde.