Overview
Escherichia coli serves as the workhorse of the global biopharmaceutical industry, used to produce everything from insulin to antibody therapies. However, this "microbial factory" has a major flaw: it struggles to export complex proteins out of the cell. Instead, valuable medicines often get stuck inside the bacteria, forming "traffic jams" (or namely inclusion bodies) that damage the cell and require expensive, wasteful purification steps to recover. Due to these limitations, current manufacturing methods are inefficient, with up to 40% of costs tied to purifying trapped proteins.
About this opportunity
This PhD project aims to address this bottleneck by engineering “Smart” secretion systems. Instead of forcing the cell to produce protein until it bursts, you will design genetic circuits that act like intelligent traffic control—driving more efficient protein secretion and sensing extracellular changes to automatically adjust production to maintain smooth, continuous secretion. By enabling E. coli to secrete recombinant proteins directly into the culture media, your research could drastically lower the cost of making life-saving biologic products and industrial enzymes, making them more accessible and sustainable.
This is a multidisciplinary project combining Synthetic Biology, Machine Learning (AI), and Industrial Biotechnology. You will:
· Design with AI: Use state-of-the-art machine learning models to generate thousands of novel “signal peptides” optimised to guide proteins out of the cell.
· Build Genetic Circuits: Engineer a “pressure valve” feedback loop using CRISPRi. This system will sense stress in the cell’s export pathway and autonomously throttle gene expression to prevent clogging.
· Test & Scale: Validate your tools by producing high-value therapeutics, in collaboration with our industrial partner, Croda. You will test the generated strains in scale-up bioreactors to prove they can outperform current industrial standards.
You will join the BBSRC CODE-M Doctoral Training Programme, a unique partnership between the University of Liverpool, the University of Manchester, and major industry partners. You will receive:
· Hands-on Training: Master gene editing (CRISPR), microscopic imaging, multi-omics analysis, and automated “bio-foundry” robotics.
· AI Skills: Learn to apply machine learning to biological design, a highly sought-after skill in modern biotech.
· Industry Experience: Working closely with Croda will gain insight into real-world biomanufacturing and scale your discoveries from the lab bench to the bioreactor.
Applicants are expected to hold (or about to obtain) a minimum upper second-class undergraduate honours degree (or equivalent) in molecular biology, microbiology, genetics, biotechnology. Research experience in genetic modification of E. coli is desirable.