Education: discovering the power of genetics

David has always had an interest in science since he was young but did not know exactly what career he wanted. All that he knew when he left school was that he really wanted to work with animals so landed up studying biology at university. Following his undergraduate degree, David did a master’s degree in zoology. For his master’s he became involved in looking at the population structure and breeding habits of seals. Because seals spend most of their life in the ocean, which makes them hard to observe, David’s research focused on investigating the genetic patterns found in samples previously collected by his supervisor. The genetic work proved highly rewarding for David because he says it allowed him to find things that he would otherwise not have found through field work. From then on David says he was hooked on genetics.

After completing his master’s degree, David undertook a doctorate looking at how genetics affects the fitness of a species. In particular he was interested in the impact of inbreeding, which, because it commonly causes ill-health and a reduction in fitness in most species, has major implications for how to handle the conservation of endangered species. His research focused on the banded mongoose. Because they often engage in incest due to their social structure, the banded mongoose were an ideal species for studying the evolution of inbreeding and fitness. David discovered that good care of offspring could often offset the negative impact of inbreeding in the mongoose and that the species adapted their breeding habits according to their environmental conditions.

Taking the stepping stone into industry

Once David had completed his doctorate, he began looking for opportunities where he could apply his genetics skills to help improve human health. To this end he began hunting for positions with biomedical and biotechnology companies. His first job was with DIOSynVax, a small biotechnology company spun out of Cambridge University to advance a multi-step vaccine technology developed by Professor Jonathan Heeney, Head of the Laboratory of Viral Zoonotics at the University of Cambridge. The advantage of the technology is that it provides a means to make vaccine candidates much faster and with much broader protection than traditional vaccines. Importantly it makes it possible to design vaccines against emerging diseases with potential to cause pandemics.

DIOSynVax uses computer modelling to analyse the structure and evolution of a virus and its relatives to create synthetic antigens, a type of protein from the virus that helps trigger an immune response. These are designed to induce the broadest protection possible and not cause unwanted harmful effects. A key piece of genetic code from the antigen is then inserted into a pre-developed vaccine delivery platform, which once administered to a person can train their immune system to recognise and block key regions of the virus which does not mutate. The end result is known as a synthetic antigen vaccine. One of the advantages of synthetic antigen vaccines is that once the manufacturing process has been established, it can be quickly and cheaply adapted to produce a different vaccine. All that is needed is to simply replace the viral antigen coding region in the delivery platform.

When David joined DioSynVAX, in September 2019, the company had only been up and running for two years so its team was still very small. What he particularly liked about the company was that its working environment was very similar to what he had experienced in academia and everyone enjoyed what they were doing. Many of those involved in the company in fact happened to be PhD students and postdoctoral researchers in Heeney’s laboratory.

DioSynVAX was also ideal because it offered David the chance to deploy his expertise in genetics as well as statistics and computer coding which he had taught himself during his doctorate. David was specifically hired to help design the synthetic antigens to insert into the company’s pre-developed vaccine delivery platform which is essentially a parcel of DNA.

A universal influenza vaccine

Among the first antigens David was asked to help design were for a universal influenza vaccine. Influenza, or flu, is a highly contagious respiratory infection caused by four types of influenza virus which typically strike in winter months. Able to cause severe illness or death, especially in very young children, the elderly and people with chronic medical conditions, influenza poses a major disease burden to the world every year and always threatens to spill over from animals into humans and create a pandemic. The World Health Organization estimates that 1 billion people get infected annually with influenza, resulting in 3-5 million cases of severe illness and up to 650,000 respiratory deaths.

Part of the problem is that influenza viruses are constantly changing, producing new strains which humans have no immunity against. This means that influenza vaccines need to be updated every year which is time-consuming. Also its effectiveness varies enormously from year to year because it is not always easy to predict which strains will be in circulation. One way round this is to create a universal influenza vaccine which can prime the immune system against a range of flu strains so that people would not need to be vaccinated each year.

A COVID-19 vaccine

David did not get very far with the universal flu vaccine because within months of starting DioSynVAX quickly switched its focus to producing a vaccine to help deal with the unfolding COVID-19 pandemic caused by the new SARS-CoV-2 virus. In late January 2020 David began contributing to the company’s development of synthetic antigens for a COVID-19 vaccine. Grateful to have the chance to make a real-difference to the world’s emergency, this work had many parallels with what he had been doing for the universal flu vaccine. But its importance felt much more pressing. It was also much more challenging because unlike flu, where there was a lot of previous data to draw on, very little was known about the SARS-CoV-2 virus.

David worked very closely alongside the wet laboratory scientists who are growing different vaccine candidates in plates. He also performed analysis on cells taken from mice that had been vaccinated to determine which part of the protein, or antigen, their immune system responded to. Although daunting, David really enjoyed the COVID-19 work because every day he and the team were discovering new things.

By December 2021 the company had successfully developed a COVID-19 vaccine suitable for testing in clinical trials. Designed to incorporate parts of the SARS-CoV-2 virus that are similar across different coronaviruses, it offered the potential of long-term protection from different coronaviruses and a stepping stone towards the development of a universal coronavirus vaccine. The vaccine also has the attraction that it can be manufactured and stabilised in powder form so does not need reliable cold-chain storage. In addition it can be delivered using a needle-free device and is cheap to produce. This makes it an ideal candidate for boosting vaccination in low and middle incomes.

Transitioning to working for a larger company

In September 2021 David moved to Vaccitech, another biotechnology company specialising in immunotherapies which include vaccines. Now known as Barinthus Biotherapeutics, the company was founded in 2016 on the back of a novel viral vector technology platform, known as ChAdOx1, developed and patented by Sarah Gilbert and Adrian Hill, two vaccine scientists based at the Jenner Institute, the University of Oxford. Taking two decades to create, their platform was specifically designed to trigger strong T cell responses against different antigens, including those found on viruses and cancer cells. The advantage of the platform is that it can be easily adapted for different diseases by changing the genetic instructions for the target antigen. With this platform the company had at its fingertips an ideal means for rapidly rolling out vaccines on an industrial scale to emerging pathogens likely to cause a pandemic. It could also be used to create cancer vaccines. Also known as immunotherapy, cancer vaccines are designed to prime the patient’s own immune system to recognise and destroy their tumour cells.

By the time that David joined the company, Vaccitech was expanding rapidly, helped by the funding it raised from the stock market to help it develop a universal flu vaccine. The company had also grabbed news headlines because AstraZeneca had licensed its platform to create a COVID-19 vaccine which began to be rolled out successfully from December 2020. For David the transition to Vaccitech took some adjustment because its workforce is much larger than in his previous workplace which meant it took him longer to get to know people. But he has enjoyed the challenge and finds it an exciting space to be in. Being part of a larger company also means he has the opportunity to learn skills from lots of different people.

David does a lot of his work at home, but two days a week he meets with the team working in the laboratory testing out the different vaccine candidates. They regularly report to him how fast each one was growing and then he carries out DNA sequencing on it to work out if its behaviour was affected by changes in their genomes. For him this is a perfect combination because it allows him the space to put his head down and focus while also having contact with people when needed. This prevents him from feeling isolated.

Excitement about bioinformatics

What David likes about being a bioinformatician is that he can apply his skills to so many different areas. He says that essentially bioinformatics is ‘just doing biology on a computer’ and ‘using programming to answer biological questions’. In his case, a lot of his time is spent reviewing literature and reading through papers to help identify possible targets for a disease and then using computer modelling to design a suitable antigen to incorporate into the vaccine platform. Once made, he then uses the computer to work out what is happening genetically in terms of the immune response to the antigens incorporated into vaccine candidates. David particularly enjoys the process of pulling together different bits of data to try and figure out how to resolve problems.

One of the attractions of bioinformatics for David is that all that he really needs for his work is a computer. This is extremely attractive for him as it means he can work anywhere, including at home. It also has the advantage that he does not require access to a laboratory to find out new things. All that he needs is to have an idea and then he can use programming to test it out. He is also really excited by the advances in DNA sequencing technology and AI which is opening up new possibilities for bioinformatics and biomedical breakthroughs.

Tips for people seeking a biomedical career

For anyone considering a career in the biomedical sector, David thinks that studying science at school and university can be very helpful. He also believes that having a good grasp of maths is highly beneficial as is having a knowledge of statistics. Another tip he would give is to get involved in lots of different types of projects because they provide opportunities to learn new skills. In his case he did a number of projects on the side while studying at university. This included developing a website which gave him the chance to learn computer coding. Largely self-taught, this skill proved invaluable to David’s master’s work and also for his job applications.

One of the biggest tips David would give to graduates wishing to get a job in industry is beginning to look through the types of jobs offered on platforms like LinkedIn. He advises doing this early before actually applying for jobs so that they can get a sense of the types of skills companies are looking for which they can then polish up before they submit an application. When they come to make the application, he advises graduates not only to cite their academic coursework, but also to highlight any side projects that they may have undertaken which can demonstrate what expertise they have in certain areas.

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This article was written by Dr Lara Marks based on an interview conducted with Dr David Wells on 30th June 2023.