Kirby Swatek's Research Group

Topic: 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.


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.

Swatek Lab
Swatek Lab


Jessica Rowe | PhD Student
Matthew Simmons | Technician
Iona Wallace | PhD Student

Selected Publications

  • Wallace I, Baek K, Prabu JR, Vollrath R, Gronau SV, Schulman BA, Swatek KN (2023) Insights into the ISG15 transfer cascade by the UBE1L activating enzyme Nature Communications  14 1-13 doi:10.1038/s41467-023-43711-3 PMID: 38042859
  • Frauenstein A, Ebner S, Hansen FM, Sinha A, Phulphagar K, Swatek KN, Hornburg D, Mann M, Meissner F (2021) Identification of covalent modifications regulating immune signaling complex composition and phenotype Molecular Systems Biology  doi:10.15252/msb.202010125 PMID: 34318608
  • Visser LJ, Aloise C*, Swatek KN*, Medina GN*, Olek KM*, Rabouw HH, de Groot RJ, Langereis MA, de los Santos T, Komander D, Skern T, Kuppeveld FJM (2020) Dissecting distinct proteolytic activities of FMDV Lpro implicates cleavage and degradation of RLR signaling proteins, not its deISGylase/DUB activity, in type I interferon suppression Plos Pathogens  doi:10.1371/journal.ppat.1008702 PMID: 32667958
  • Alix E, Godlee C, Cerny O, Blundell S, Tocci R, Matthews S, Liu M, Pruneda JN, Swatek KN, Komander D, Sleap T, and Holden DW (2020) The tumor suppressor TMEM127 is a NEDD4-family E3 ligase adaptor required by a Salmonella effector to ubiquitinate and degrade MHC class II molecules Cell Host and Microbe 28 54-68 doi:10.1016/j.chom.2020.04.024 PMID: 32526160
  • Ordureau A, Paulo JA, Zhang J, An H, Swatek KN, Cannon JR, Wan Q, Komander D, and Harper JW (2020) Global landscape and dynamics of parkin and USP30-dependent ubiquitylomes in iNeurons during mitophagic signaling Molecular Cell 77 1124-1142 doi:10.1016/j.molcel.2019.11.013 PMID: 32142685
  • Swatek KN, Usher JL, Kueck AF, Gladkova C, Mevissen TET, Pruneda JN, Skern T, and Komander D (2019) Insights into ubiquitin chain architecture using Ub-clipping Nature 572 533–537 doi:10.1038/s41586-019-1482-y PMID: 31413367
  • Damgaard RB, Elliott PR, Swatek KN, Maher ER, Stepensky P, Elpeleg O, Komander D, and Berkun Y (2019) OTULIN deficiency in ORAS causes cell type specific LUBAC degradation, dysregulated TNF signaling and cell death EMBO Molecular Medicine 11 doi:10.15252/emmm.201809324 PMID: 30804083
  • Pruneda JN, Bastidas RJ, Bertsoulaki E, Swatek KN, Santhanam B, Clauge MJ, Valdivia RH, Urbe S, and Komander D (2018) A Chlamydia effector combining deubiquitination and acetylation activities induces Golgi fragmentation Nature Microbiology 3 1377-1384 doi:10.1038/s41564-018-0271-y PMID: 30397340
  • Swatek KN, Aumayr M, Pruneda JN, Visser LJ, Berryman S, Kueck AF, Geurink PP, Ovaa H, van Kuppeveld FJM, Tuthill TJ, Skern T, Komander D (2018) Irreversible inactivation of ISG15 by a viral leader protease enables alternative infection detection strategies Proc Natl Acad Sci U S A  115 2371-2376 doi:10.1073/pnas.1710617115 PMID: 29463763
  • Annibaldi A, John SW*, Berghe TV*, Swatek KN*, Ruan J, Wu H, Liccardi G, Bianchi K, Komander D, Choi SM, Coille SV, Vandenabeele P, Bertin J, Silke J, and Meier P (2018) Ubiquitin-mediated regulation of RIPK1 kinase activity, independent of IKK and MK2 Molecular Cell 69 566-580 doi:10.1016/j.molcel.2018.01.027 PMID: 29452637
  • Michel MA, Swatek KN, Hospenthal MK, and Komander D (2017) Ubiquitin linkage-specific affimers reveal new insights into K6-linked ubiquitin signaling Molecular Cell 68 233-246 doi:10.1016/j.molcel.2017.08.020 PMID: 28943312