Dr Kirby Swatek

Principal Investigator

MRC PPU, School of Life Sciences

Kirby Swatek

Contact

Email

[email protected]

Phone

+44 (0)1382 385844

Websites

Swatek Lab

Biography

Kirby is originally from St. Louis, Missouri, USA. In 2007, he graduated with a BS (Hons) in Biochemistry from the University of Missouri. In 2013, he completed his PhD in the same institute under the guidance of Jay Thelen. Here his PhD research focused on applying state-of-the-art proteomics and mass spectrometry techniques to unravel the phosphorylation networks of Arabidopsis seed development.

After completing his PhD, Kirby joined David Komander's lab at the MRC Laboratory of Molecular Biology in Cambridge, UK, to study the complexity of the ubiquitin system. Here he developed innovative proteomic approaches to identify and understand the architecture of polyubiquitin chains, which provided critical insights into how these complex signals function in cells. In 2018, he joined Brenda Schulman's Department at the Max Planck Institute of Biochemistry in Munich, Germany, to pursue his interests in structural biology of multiprotein complexes of the Ub/Ubl system. Kirby started his research group in the MRC Protein Phosphorylation and Ubiquitylation Unit at the beginning of 2022.

Research

Ubiquitin-like signalling in the immune system

In response to viral infection, cells launch sophisticated defence mechanisms to combat the invading pathogen. The antiviral state is one mechanism that results from global changes in gene expression and extensive remodelling to the landscape of post-translational modifications. Ubiquitin (Ub) and ubiquitin-like protein (Ubl) modifications are crucial signals in this defence response, and therefore, the misregulation of these signalling pathways can have dire consequences, namely increased disease severity.

A central player of the antiviral state is a ubiquitin-like protein, ISG15, which marks thousands of proteins in response to viral infection. To evade this defence response, many viruses suppress ISG15 signalling by removing these modifications with viral proteases. However, despite their abundance and clear viral evasion strategies, the roles of ISG15 modifications remain surprisingly enigmatic. We are fascinated by ISG15's role in the antiviral state and excited to study this underexplored area of innate immune signalling. The long-term goal of the Swatek lab is to visualize the ISG15 system and understand the roles of these modifications in the antiviral state.

Current research focus:

  1. Structural analysis of the writers, readers, and erasers of the ISG15 system
  2. Immunomodulatory functions of ISG15
  3. Viral manipulation of the ISG15 pathway
  4. State-of-the-art method development to study Ub/Ubl modifications

Our research has already revealed fascinating new insights into Ub/Ubl biology and exposed unexpected viral evasion strategies. These discoveries have prompted us to rethink the arms race during pathogenesis, including how the host defends against viruses and how viruses escape the host defence systems. We believe our findings have only scratched the surface and that many unexpected and exciting discoveries are still to come, some of which may lead to the development of new therapeutics.

Values

We are committed to building a lab culture that actively promotes equality, diversity, and inclusion to make progress in science. This commitment will foster a creative and supportive environment that encourages individuals to think freely, express themselves openly, and exchange ideas with mutual respect. We welcome applicants from underrepresented and disadvantaged backgrounds. If you are interested in joining the team, please get in touch.

View full research profile and publications

Awards

Award Year
Major Personal Funding Awards / Lister Research Prize 2023

Stories