Meet the 2024 Microbiology Society Prize Medal Winner, Professor David Holden

03 April 2024

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Each year the Microbiology Society awards the Microbiology Society Prize Medal to an outstanding microbiologist who is a global leader in their field and whose work has had a far-reaching impact beyond the field of microbiology. 
Ahead of the Prize Medal 2024 lecture early career member, Ellie Foster, interviewed Professor David Holden to learn more about his career and how it feels to win a Microbiology Society prize.

How did you feel when you found out you won the Prize Medal?

Surprised and delighted. I gave my first presentation – a short talk – at a Microbiology Society meeting when I was a PhD student, and I have been a member of the Society for most of my career.  I very much appreciate the Society’s work and its journals, and I feel honoured to be awarded the prize.

What will you be talking about in your Prize Medal Lecture at Annual Conference 2024?

I have always loved genetic screens. That has been my thing and they have been a big part of my career, so I will be talking about three screens, and how they have shaped my approaches and what we have discovered as a result.

One of your career highlights to date was the development of the signature tagged mutagenesis technique. How do you think this has impacted your career and influenced future research?

That was in 1995, so it was quite a few years ago! It was transformational for me – it made me realise I could do original science, but I have to say it took a long time to get to that point. It involved a lot of failures and many long hours of thought and reflection on what I was doing.

I ended up being lucky, as the application of the barcoding technique to Salmonella really developed a pot of biological gold, which was the SPI-2 Type III secretion system that we, and many others, have been studying ever since.

What is the most interesting fact about Salmonella you have discovered during your career?

There are many. It has such amazing and sophisticated biology for such a little bug. For many millions of years, it has been responding to selective pressure in mammals and as a result, it has evolved fascinating biochemical mechanisms, enabling it to grow in host tissues whilst suppressing innate and adaptive immune functions.

A big surprise to me was that very potent activities that can change the physiology of cells can be caused by small, non-enzymatic Salmonella proteins which are injected into the host cell via the type III secretion systems.

Where do you see the field heading and where do you hope your research will lead in the next decade?

No idea! It is a tough one to predict. Obviously, I hope there will be a more complete understanding of bacterial virulence. In the case of Salmonella, we now know most pieces of the puzzle, such as many of the biochemical activities of the proteins required to mediate virulence. However, how they all fit together in time and space and how they are coordinated are yet to be determined. That will happen and it will be a huge scientific advance – not just for the field of microbiology.

What is the biggest challenge in the field right now?

Making sense of huge data sets generated by high throughput technologies and keeping up with the progress in the field I would say are some of the many challenges. When I started working on Salmonella 30 years ago, the key literature consisted of a handful of papers. It was nothing like the sea of papers today. Finding and navigating your way through that now is a daunting challenge.

Review articles can help a lot with this, but they do not capture everything and they are no substitute for reading the primary literature.

How important do you think mentors are for the success of an individual’s carer? How have mentors guided and supported you?

Mentors can (and should be) incredibly useful. I have to say, I did not have a mentor in my PhD and postdoc years because it wasn’t fashionable back then to have mentors. I think to have somebody who would have encouraged and guided me would have been a huge support. It would have allowed me to go through difficult periods with a more positive outlook. But again, on the other hand, maybe I would have been less self-reliant.

Science is particularly prone to disappointment when it comes to results – that is the nature of the game. It can be disheartening, particularly if it goes on for a long time. However, sometimes that happens, and you have to trust yourself. To have somebody there saying do not be too concerned about it, we all go through it, can be hugely beneficial.

Who would you say has had a major influence on you during your career?

All the way through my career, people have influenced me. They have not been mentors, but I have looked to them, and they have inspired me.

I suppose going back to the beginning, my father was a geneticist and he early on showed me how genetics was so powerful and so beautiful at the same time. Those two things really stuck with me, and I think it subconsciously aligned me towards a career in that direction.

Other people who have made a big impression on me include Barbara McClintock – she discovered transposable elements and was arguably the first person to show gene regulation. At the time, she was misunderstood, and she did not get the credit she deserved until much later when she won a Nobel Prize for the discovery of transposable elements. She was an amazing woman and a brilliant scientist. There was much more to her than the science – it was her character that also had an impression on me.

Stan Falkow was one of the true pioneers of cellular microbiology and is considered by many to be the father of the field. When we published the barcoding paper and found the SPI-2 system, he was extraordinarily gracious and welcomed me to the field (because we had been working on fungi previously). This was our first paper on Salmonella, and I was an outsider to that field. He welcomed me, and he became a good collaborator and a friend.

And finally, the great science philosopher Karl Popper. He is always there in the background, looking over your shoulder and keeping you honest and sceptical about everything.

What were your early career aspirations? How have they changed as you have progressed through your career?

As a PhD student and postdoc, all I ever wanted was to get a permanent job as a scientist or as a lecturer. Anywhere! I did not care! For several years, that was my aim. I was worried if I was employable as a scientist and that is the honest truth. I had a lot of self-doubt and misgivings about my own ability, but for many years that was my sole aim.

As I grew as a scientist, I wanted to be able to show that I could do good science. I wanted to be able to discover things that were interesting and hopefully useful at some point.

I didn’t have a huge amount of ambition beyond wanting to have the freedom to direct my own research. I will never forget walking into my own lab on the first day when I was at the Royal Postgraduate Medical School, at Hammersmith Hospital. I had got this job as a Lecturer, and I had my own lab! I could walk into the lab and do what I wanted. That was amazing, it really got my heart racing. And I thought - what a privilege to be a scientist! All the heartache, anxiety and sleepless nights were worth it in the end to get to that point.

What advice would you give to an aspiring microbiologist?

It’s a tough job leading an academic research group. The thing that concerns me a lot is that so many things get in the way of doing science. By science, I mean from chatting to people over coffee about research, ideas, just stuff that comes into your head, both inside and outside your field of interest. That very informal environment is where ideas get generated. Plus doing experiments, grant and paper writing, supervising, reading. All these things are part of the job of doing science. But it becomes difficult when there’s so much other stuff that gets in the way (administration, bureaucracy, regulatory hoops that you have to jump through). All of these things can make the job very daunting and frustrating.

So, one thing is that you have to love it. You almost have to be obsessed by it. If you are waking up in the morning and you cannot wait to get into the lab to find out what the result of your experiment is, that is a very good sign. It shows that you are inherently curious, and you are going to enjoy it, so you can put up with all the impositions on your time.

It sounds a bit trite, but I think reading and thinking are two of the most precious commodities that you can have as a young scientist. So, my advice would be to make sure they get plenty of your time.

Overall, how would you describe your career?

I have been extraordinarily lucky throughout my career. We were lucky in discovering the SPI-2 system in the genome of Salmonella. That was just a stroke of great good fortune. But luck has also come from the people I have worked with. I have had the pleasure of working with some truly inspiring scientists, remarkable people really, consistently, right from the very beginning and who have been an absolute joy to work with. So, they deserve a huge amount of credit for the work we (mainly they) have done. There is no question about it, I would not be here talking with you and accepting this award if it weren’t for them.