Using baker’s yeast to develop reference viral antigens of SAR-CoV-2
Aligned with our mission to advance the understanding and impact of microbiology, the Society reached out to our community of microbiologists to share their experiences in responding to SARS-CoV-2. We aim to showcase the perspective of scientists during the COVID-19 pandemic and the variety of roles adopted to mitigate the global crisis.
This case study is written by Professor Ed Louis of the University of Leicester and Chief Scientific Officer of Phenotypeca Ltd, UK. Ed’s account highlights how collaboration between academia and industry can aid innovation, the challenges of establishing new working practices during lockdown and the joy of getting his hands dirty at the lab bench after many years.
How did you respond to SARS-CoV-2 during the COVID-19 pandemic?
In May 2019, I semi-retired from the University of Leicester and became Chief Scientific Officer of Phenotypeca Ltd. Phenotypeca is a biofoundry that combines synthetic biology and advanced breeding of diverse baker’s yeast to develop strains for heterologous protein production in particular vaccines and other therapeutics, with a mission to make these more affordable for all.
As the world became aware of SARS-CoV-2, and sequence and protein structure information became quickly available in early 2020, we realised that our platform for developing new, improved yeast production strains could be used to produce viral proteins for use as reference antigens and we started planning for this before lockdown. We applied for and were awarded funding for an Innovate UK “Business-led innovation in response to global disruption” to do this in partnership with the Jenner Institute, UK. We succeeded in expressing various parts of the spike protein and improved that expression through our breeding strategy. Although at the time the UK government’s efforts moved away from producing reference antigens for testing, this success underpinned further developments in improved yeast for use in vaccine formulation and therapeutics and we have been awarded several grants, including a Bill and Melinda Gates Foundation award for low cost vaccine development.
Was this response related to your work prior to the outbreak?
Just prior to the outbreak, the University of Leicester and Phenotypeca signed a collaborative agreement where strain development and breeding for the company would be done in my lab at the University. This was all based on my last 15 years of research in the genetic and phenotypic diversity of baker’s yeast, Saccharomyces cerevisiae, and so was directly related to both my recent research as well as the basis of the company’s research and development platform.
What were some of the challenges that you faced during this time?
There were of course the obvious challenges, the main ones being access to lab facilities and the ability to safely travel to and work in the lab. Because we had the rapid response award and the collaboration with the university, I was designated as a critical worker and could return to the lab earlier than many of my colleagues or indeed any of my lab members. As this was all new to everyone, there was a lot of work involved in planning, assessing suitability of the labs (ventilation, spacing, movement through, etc.), risk assessments, contingency planning, safety training (new procedures), tracking and reporting. This took months of behind the scenes work by many before the lab became accessible and the first researchers allowed back.
How did your experience throughout the response aid in your development?
I was very fortunate to be in the first group of researchers to return to the lab and worked essentially alone for a few months except for a few other critical workers in the building. Part of being in the first group to return was the assessment of the procedures put in place, to see if they were suitable for the return of the other members of the lab, all suffering from an inability to work on their PhD projects, as well as planning when individuals would return and where they would be. This had to be coordinated with other groups in the lab, on the same floor and in the building.
After many years, I was back at the bench doing what I love, but also doing something that could be important and was simultaneously helping the development of the company. This made me realise what I had been missing for decades as a Professor and Principal Investigator: being at the bench doing research with my own hands. Since then, I am continuing to retain time at the bench myself, and will continue until retirement, whenever that may be.
What can we learn about the importance of microbiology from the COVID-19 pandemic?
For me, the important lesson society learned from the pandemic is to trust science and scientists again. Microbiology is at the centre of this. It may be that governments in general are not always ‘following’ the science but people in general have become much more aware of hygiene issues with face masks, hand sanitisers, maintaining social distance, as well as the mechanics of aerosol movements, R-numbers, etc. I think people are now much more educated about viruses and epidemiology and this understanding will apply to microbiological issues in general and future pandemics/epidemics.
How did the Microbiology Society play a role in your response?
My colleagues in the Society, particularly those of the Virology Division, provided a fount of knowledge in times of uncertainty. The members are behind the science that should be followed. The Society was and is a leading example of following this science and helps in disseminating sound information to the population.
About the author
Ed Louis is a Professor of Genetics at the University of Leicester and Chief Scientific Officer of Phenotypeca Ltd. You can find out more about his research into the genetic and phenotypic diversity of baker’s yeast.