Meet the 2024 Microbiology Society Marjory Stephenson Prize Winner, Professor Maggie Smith
01 April 2024
The Marjory Stephenson Prize is the principal prize of the Microbiology Society, awarded for an outstanding contribution of current importance in microbiology.
Ahead of the Marjory Stephenson Lecture Dr Razan Abbara interviewed Professor Maggie Smith to learn more about her career and how it feels to win a Microbiology Society prize.
Congratulations on winning the Marjory Stephenson Prize! How do you feel about being one of the 20 microbiologists who have received this Prize and what does it mean to you?
I felt honoured, humbled, and terrified. All those things!
What made you feel terrified?
Giving the Prize Lecture is going to be quite terrifying because the pressure is quite immense. However, I am mostly honoured and humbled being next in line to previous winners, all of whom are interstellar in what they have achieved.
What made you choose to work on antibiotics specifically in your PhD and your research after?
I am a curious person and I like to ask questions. When I finished my undergraduate degree, I was very curious about how macromolecules get across membranes. One of my lecturers in Leeds was an inspiration as he talked about how transport proteins escort molecules across membranes.
Then I came across this PhD position in Bristol, where they were studying how antibiotic efflux occurs – a mechanism that confers resistance. But I really wanted to know why bacteria take up antibiotics that are going to kill them in the first place - and in a process that uses energy to do so. That really tickled my curiosity and I really wanted to know the answer, so I went to Bristol to do that project.
After I finished my PhD, the exciting field in microbiology was the emergence of molecular biology, such as cloning. My PhD was in biochemistry, but I wanted to learn these new techniques in Molecular Biology, so I switched fields.
I went to Leeds to do a post-doc with the late Professor Simon Baumberg and learned some molecular genetic techniques by working on a regulatory system in Bacillus. When I finished that post-doc, I was lucky enough to get a semi-independent post in Glasgow with Professor Iain Hunter, and he worked on Streptomyces.
In my earlier environments, both in Bristol and in Leeds, they both had projects going on around me on Streptomyces bacteria, so I could see that Streptomyces are important organisms because they produce antibiotics. I have never thought about that before. I thought this opportunity in Glasgow was perfect. I am going to work on Streptomyces, which is a difficult organism to work on, and I liked the challenge. I thought it was great and I could choose my own project. All the people around me worked on antibiotic biosynthesis, which is incredibly important. However, I did not have the skills to find my own project in that area at that time, and being awkward, I wanted to find something that I could call my own. I chose to work on a phage regulatory system. Phages are very useful as resources for tools for molecular biology, so I started working on bacteriophages of Streptomyces.
Why did you choose to become a lecturer?
I had the opportunity to work in industry, and the most tempting was to work on Bacillus thuringiensis and the crystal toxins. However, the idea of being told what to do did not sit well with me. I needed the academic freedom to ask questions - to be curious and do my own research. It was needing that freedom to work on whatever I found most interesting.
You experienced a stopgap because of the work on fC31 phage of Streptomyces sp. What did you learn from this and what can early career researchers get from having unplanned stopgaps?
In my case, learning about fC31 was the way to learn about Streptomyces. I had envisaged that at some point I was going to work on antibiotic biosynthesis because that is what most people do when they work on Streptomyces. I thought in the future I would have the skills to be able to work on antibiotic biosynthesis and I never really got there. It was not that I did not learn the skills, I just found the entire process of phage replication in this organism to be interesting, so we had the opportunity to work on a novel biological system that became my entire career. So, it was not really a stopgap at all. All the various aspects that we worked on just led to new biology.
A stopgap for anybody is a way that you can start to learn something new and transfer your career to a new area. In fact, I had to learn some new fields, and the people around me had to learn. If you continue working on the same things, using the same techniques, you will lose your curiosity that drove you in the first place. New projects, new areas, new fields are stimulating and a challenge, but can also be hard.
Since you worked on serine integrase as a genetic engineering tool for finding new antibiotics, do you think finding new antibiotics is the solution to antimicrobial resistance (AMR)?
Partly! I think it is complicated. Yes, we need new antibiotics, but I think the situation is a little bit more nuanced than that. We need to take care of the antibiotics we have now, and we need to understand the evolution of AMR better than we do. I think we need to be aware of when we are putting selective pressure on the bacterial population that is causing pathology. We also need to be much more aware of why these resistant bacteria emerge. We need to invest in new antibiotics, and we cannot leave them to the market forces because fewer pharmaceutical companies are putting investment into new molecules. We need to take advantage of new processes like artificial intelligence for designing new molecules – an area which is very promising. We need to think much harder about infection control and what is happening in the environment. As I said, it is complicated!
What do you think about using CRISPR-CAS as a tool to combat antimicrobial resistance (AMR)?
It is a phenomenal tool. Very clever people have exploited CRISPR-CAS in such a way to make it very versatile and somebody may come up with a way of using CRISPR to combat AMR – they may already have done so. But as I see it bacteria are incredibly good at acquiring genes and mutating genes, and they become antibiotic resistant much faster than we can use a tool like CRISPR.
Since I am not an expert in CRISPR, I am not sure how it can be sufficiently efficient against AMR. However, if you combine CRISPR with phage and phage therapy, then it might work. Phage therapy is a way of using bacteriophage to kill bacteria or to make them less evolutionary fit. Maybe a combination of CRISPR with phage will be an efficient way to deliver such a tool. But phage is already quite good at killing bacteria. There is an exciting symposium at the meeting in Edinburgh talking about that, and I am looking forward to finding out whether anybody has combined phage therapy with CRISPR, or whether phage therapy becomes a routine therapy against AMR.
Which is the most promising in your opinion, protein glycosylation or CRISPR-CAS?
The reason we pursued protein glycosylation was partly because we were driven by understanding the phage life cycle. The phage needs that pathway to have a successful infection. But we also noticed that the mutants that could not support infection also grew slowly, and they were hypersensitive to antibiotics, so clearly there is a fitness cost of becoming resistant to the phage.
We were interested to see if it would be possible to create molecules that inhibit the protein glycosylation pathway in some way, so the bacteria would become desensitised to antibiotics. In Streptomyces coelicolor there is a vancomycin resistance pathway and the whole pathway is undermined completely by the mutations in the protein glycosylation pathway. Vancomycin is one of the best antibiotics against gram-positives. If we can find out the mechanism behind undermining this pathway, then maybe we can create chemicals that could copy that, and we could use them alongside vancomycin in the same way that we use penicillin analogues such as augmentin.
It was Women in Science Day on 11 February 2024. How do you feel about being a woman in science?
I have been thinking about this question a lot before you asked. I have been thinking about whether there is still a problem in science. I have to say first, all scientists are very broad-minded, and very fair. Scientists are generally egalitarian, non-racist, non-prejudiced in any way against any kind of person or their beliefs. Being open-minded is in the nature of scientists. That is what has driven me all the time. Although I have had instances where I felt a little bit side-lined or uncomfortable, they are very rare. I think I have been lucky that I have not suffered obvious unfairness.
Do you have any advice that helped you when you were an early career researcher?
You need to be curious, observant, ask questions, and then you need to focus. You need to focus on papers. Your priority is to go to delivering papers. That is the piece of advice I wish I had when I was a young lecturer. Focusing on the story that delivers the paper is incredibly important because that means that you do not waste your time, and the time in the lab is very precious, as we know from COVID. Do not waste your time doing little side projects that are not going anywhere.
Having a mentor is important as well, somebody to be honest with you about where your skills are, to find out for you what you are really interested in. It is only then that you are going to work your hardest and focus your mind. So, CURIOSITY AND FOCUS!
