Earlier this month, our Chair Professor Sir John Iredale and Director Dr Sally Burtles visited 2023 Lister Fellow Kirby Swatek at his home institution, the University of Dundee. `They were pleased to present him with the Lister Prize and hear a seminar on his research.
Kirby is Principal Investigator at the university’s MRC Protein Phosphorylation and Ubiquitylation Unit, based within the School of Life Sciences. He shared some thoughts with us on the visit and how the Lister Prize has enabled his research so far.
Q: Can you tell us more about the Prize Visit?
A: The day was quite easy-going, with plenty of time to catch up with John and Sally, show them around the institute, and introduce them to my lab and colleagues. The seminar was an excellent opportunity to update them on my research, future directions, and the research projects funded by the Lister Institute. I was thrilled to see so many of my colleagues in attendance at the seminar, which I think is a testament to the supportive atmosphere of the MRC Protein Phosphorylation and Ubiquitylation Unit and School of Life Sciences at the University of Dundee.
Q: How did it feel to formally receive the Lister Prize?
A: John’s remarks during the award presentation ceremony were extremely supportive of my research and career development. It was interesting to hear him speak about the rich history of the Lister Institute and the many distinguished scientists that have been associated with the organisation over the years. All these factors made me appreciate what a tremendous honour it is to receive a Lister Prize.
Q: What are you and your lab team currently working on?
A: My team is focused on understanding the biology of a ubiquitin-like protein called interferon-stimulated gene 15, or ISG15. ISG15 has emerged as a key player in the innate immune response due to its high level of expression following viral infections, attachment to hundreds of substrates, and ability to control multiple aspects of immune signalling.
Moreover, many viruses, including SARS-CoV2, target ISG15 to interfere with its ability to carry out immune functions. What’s surprising to me, however, is that we still know very little about the molecular details of this pathway or the “nuts and bolts” of how ISG15 protects the host cell. I always tell my students that our current understanding of ISG15 lacks mechanistic insights, and we can contribute to the field by filling in this knowledge gap. Rewardingly, my lab has already made a tremendous amount of progress in understanding the details of this crucial immune signalling pathway.
John’s remarks during the award presentation ceremony were extremely supportive of my research and career development. It was interesting to hear him speak about the rich history of the Lister Institute and the many distinguished scientists that have been associated with the organisation over the years.
Q: How has the Lister Prize funding enabled your work to date?
A: The funding has been critical in enabling us to establish a new line of research. Almost everyone in my team is focused on understanding the host defence pathways. However, what’s missing is projects on understanding how pathogens break down these defence barriers. This information is an essential piece of the puzzle to understanding how pathogens succeed in infecting cells and causing disease. With the support from the Lister Award, we have started to build this research area in my lab.
Since we’ve already developed a ton of exciting tools and reagents on the host signalling pathways, this new research area on pathogen immune evasion strategies is complementary and synergistic with our ongoing efforts. Specifically, we have initiated projects to study an unusual mechanism by which some pathogens evade ubiquitin and ubiquitin-like signalling by encoding proteases that damage these modifiers so they can no longer be attached to substrates. We refer to this unusual activity as “inactivation” of ubiquitin and ubiquitin-like proteins.
Q: What are your future plans for the funding?
A: We are excited to understand the extent to which ubiquitin and ubiquitin-like inactivation occurs in biology. Only a few pathogens have currently been reported to encode these unusual proteases, and interestingly, all of these studies have come from independent labs in different research fields, suggesting that we have only begun to scratch the surface and that other pathogens may deploy similar strategies to inactivate these defence signals. The Lister Prize is enabling us to explore this underexplored area of biology on multiple fronts, which I believe holds significant potential to reveal several important and unexpected discoveries related to infection and immunity.
The Lister Prize is enabling us to explore [an] underexplored area of biology on multiple fronts, which I believe holds significant potential to reveal several important and unexpected discoveries related to infection and immunity.
Q: How did you first learn about the Lister Prize? What motivated you to apply?
A: The first time I heard about the Lister Prize was shortly after I started my postdoc at the MRC Laboratory of Molecular Biology (LMB), when my former advisor, David Komander, gave his Lister Prize Lecture. In fact, I think this was the first seminar I attended at the LMB. In addition to the seminar being a wonderful introduction to the lab’s research, I specifically remember being impressed by how supportive the Lister Institute’s former Chair Sir Alex Markham was of David’s research and career development. I think it was this positive experience that played a key role in motivating me to apply for the award.
Q: How would you advise someone considering applying for a Lister Prize?
A: Do not hesitate. The application process is extremely straightforward. It took me about a week or two to put together my application, and since it was on a research topic that I’m extremely passionate about, the writing was relatively pain-free.
Learn more about Kirby’s research at the Swatek Lab
