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My route into science was less traditional than most. I joined Ingenza straight from high school in January 2012, choosing to take on a modern apprenticeship rather than starting a full-time degree. This work-based learning approach was a more appealing educational pathway for me, giving me the opportunity to gain practical expertise alongside theoretical knowledge. In the eight years since I joined Ingenza, I’ve worked in several different sections, learning about chemistry, protein purification and pathway engineering, eventually settling in the molecular biology department and starting to work on antimicrobial peptides (AMPs). Recently, I was awarded funding from the 1851 Royal Commission to support my PhD research, which is quite an honour and a very exciting prospect. The built-in partnership between academic investigation and industrial application promoted by the Industrial Fellowship programme is ideal.
Recently, I was awarded funding from the 1851 Royal Commission to support my PhD research, which is quite an honour and a very exciting prospect.
I’m scheduled to take up my fellowship in October 2020 and plan to continue working on AMPs, with support from Professor Mat Upton at the University of Plymouth. AMPs are generally small peptides that lyse many cell types without distinguishing between human and microbial cells. Unfortunately, this makes them unsuitable to use as medicines, as they would have adverse side-effects on patients, however, epidermicin, discovered by Professor Upton, is an exception. It displays selectivity for Gram-positive microbes such as MRSA and, crucially, shows very little haemolytic activity. Why this should be is not yet fully understood, but it is a promising discovery for the development of therapeutic AMPs. The biggest hurdle for using epidermicin as an anti-MRSA treatment is the cost of its manufacture, which was deemed prohibitively high. Working with Professor Upton, Max Ryadnov of the National Physical Laboratories, and Martyn Winn of the Science and Technologies Facilities Council, we were able to find out more about the peptide’s mechanism of action, and define a highly scalable, cost-efficient manufacturing platform to provide material for preclinical testing. The aim now is to apply the methods, expertise and production strategy from epidermicin to the discovery of more exciting AMPs that can be used to treat new and emerging superbugs and expand our biopharmaceutical repertoire even further. For example, the fellowship will allow me to investigate antibody fragment technology to create a bespoke purification platform for AMPs, helping to speed up and standardise the production pipeline for these exciting biomolecules.
The aim now is to apply the methods, expertise and production strategy from epidermicin to the discovery of more exciting AMPs that can be used to treat new and emerging superbugs and expand our biopharmaceutical repertoire even further.
Another aim of the overall project is to work on the high throughput screening of variant peptides, which are made up of the 20 natural amino acid building blocks, to see how changing their sequence affects their antimicrobial activity. The idea is to see which of the variants – all with different amino acid sequences and, therefore, chemical properties – show a novel or improved response against difficult-to-treat pathogens that have developed resistance. However, testing every peptide is simply impossible, as there are so many ways to combine the 20 natural amino acids – even for a very simple five amino acid peptide, there are 3.2 million unique sequences!
It’s important to learn as much as possible from the small number of peptides that we can test, and the best way to do this is using machine learning. The data we collect from screening will include both successful and unsuccessful peptides. This type of data is complex and has many variables, making it difficult for a human to spot patterns. This is where computer algorithms come in, as they can be developed to spot patterns undetectable by the human eye, which can then be used to interpret how changing the amino acid sequence of AMPs can make them more active towards specific pathogens.
From a personal development point of view, the fellowship will allow me to carry out more pioneering research, and to learn new techniques such as bioinformatics and machine learning. It will also give me the opportunity to develop other softer skills such as written and oral communication, which are vital in effectively communicating science and making research accessible for all. It is extremely encouraging to know that the experts at the Royal Commission can see the potential value in this research programme and I’m excited to start!