Yogesh Kulathu's Research Group

Kulathu Lab Website | Biography


Ubiquitin signalling mechanisms

Our laboratory is interested in understanding how signal transduction is mediated in cells by the posttranslational modification of proteins. A primary focus of the lab is the ubiquitin system where the attachment of ubiquitin can alter the function and fate of the modified protein. By using a multidisciplinary approach, we aim to get mechanistic insights into how fundamental cellular processes are modulated by ubiquitylation to maintain cellular homeostasis. Of late, we have also expanded our research into the poorly studied ubiquitin-like modifer UFM1 which is essential for protein biogenesis and endoplasmic reticulum homeostasis. We aim at getting detailed biochemical and molecular insights into these processes by focussing on the enzymes that add the modification, modules that recognize and decode the modification, and proteases which remove them.

At present, we have 3 focus areas of research in the lab:

  1. How do different ubiquitin signals couple to different signalling outcomes and how is ubiquitylation regulated by Deubiquitinases (DUBs)?
  2. How are proteins modified with UFM1 and how does this modification maintain ER homeostasis?
  3. How are the IRAK kinases activated and regulated in innate immune signalling?

See here for more details

From left: Top: Gaurav Anand, Linnan Chen, Rohan Thakur, Alicia Cordova Perez, Anna Perez I Rafols, Pritha Dasgupta, Helge Magnussen, Steve Matthews, Loges Krshnan. Bottom: Matt McFarland, Yogesh Kulathu, Vincent Brouwer, Ian Kelsall
From left: Top: Gaurav Anand, Linnan Chen, Rohan Thakur, Alicia Cordova Perez, Anna Perez I Rafols, Pritha Dasgupta, Helge Magnussen, Steve Matthews, Loges Krshnan. Bottom: Matt McFarland, Yogesh Kulathu, Vincent Brouwer, Ian Kelsall

People

Rohan Thakur | PhD Student
Pritha Dasgupta | PhD Student
Aiden Newell | Undergraduate Honours Student
Grace Harrison | PhD Student
Gaurav Anand | Postdoctoral Researcher
Ian Kelsall | Postdoctoral Researcher
Dr Logesvaran Krshnan | Postdoctoral Researcher
Helge Magnussen | Postdoctoral Researcher
Stephen Matthews | Senior Research Associate
Matthew McFarland | Postdoctoral Researcher
Rachel O'Dea | Postdoctoral Researcher
Anna Pérez i Ràfols | Postdoctoral Researcher
Linnan Shen | Senior Research Technician

Selected Publications

Google Scholar | PubMed

  • Lange SM , McFarland MR , Lamoliatte F , Kwaśna D , Shen L , Wallace I , Cole I , Armstrong LA , Knebel A , Johnson C , De Cesare V , Kulathu Y (2023) Comprehensive approach to study branched ubiquitin chains reveals roles for K48-K63 branches in VCP/p97-related processes   doi:10.1101/2023.01.10.523363
  • Millrine D, Peter JJ, Kulathu Y (2023) A guide to UFMylation, an emerging posttranslational modification FEBS Journal  doi:10.1111/febs.16730 PMID: 36680403
  • Peter JJ, Magnussen HM, DaRosa PA, Millrine D, Matthews SP, Lamoliatte F, Sundaramoorthy R, Kopito R and Kulathu Y (2022) Non canonical scaffold-type ligase complex mediates protein UFMylation EMBO Journal 41 e111015 doi:10.15252/embj.2022111015 PMID: 36121123
  • Millrine D, Cummings T, Matthews SP, Peter JJ, Magnussen HM, Lange SM, Macartney T, Lamoliatte F, Knebel A, Kulathu Y. (2022) Human UFSP1 is an active protease that regulates UFM1 maturation and UFMylation Cell Reports 40 doi:10.1016/j.celrep.2022.111168 PMID: 35926457
  • Lange SM, Armstrong L, Kulathu Y (2022) Deubiquitinases: from mechanisms to their inhibition by small molecules Molecular Cell 82 15-29 doi:10.1016/j.molcel.2021.10.027 PMID: 34813758
  • Syed Arif Abdul Rehman, Lee A. Armstrong, Sven M. Lange, Yosua Adi Kristariyanto, Tobias W. Grawert, Axel Knebel, Dmitri I. Svergun, Yogesh Kulathu (2021) Mechanism of activation and regulation of Deubiquitinase activity in MINDY1 and MINDY2 bioRxiv   doi:10.1101/2021.01.27.428544
  • Lange SM, Nelen MI, Cohen P, Kulathu Y (2021) Dimeric Structure of the Pseudokinase IRAK3 Suggests an Allosteric Mechanism for Negative Regulation Structure 29 1-14 PMID: 33238146
  • Armstrong, L. A., Lange, S. M., de Cesare, V., Matthews, S. P., Nirujogi, R. S., Cole, I., Hope, A., Cunningham, F., Toth, R., Mukherjee, R., Bojkova, D., Gruber, F., Gray, D., Wyatt, P. G., Cinatl, J., Dikic, I., Davies, P., & Kulathu, Y. (2021) Biochemical characterization of protease activity of Nsp3 from SARS-CoV-2 and its inhibition by nanobodies PLoS ONE 16 e0253364 doi:10.1371/journal.pone.0253364 PMID: 34270554
  • Leznicki P and Kulathu Y. (2017) Mechanisms of regulation and diversification of Deubiquitylating enzyme function J Cell Sci doi:10 1242/jcs.201855 PMID: 28476940
  • Kristariyanto, Y. A., Abdul Rehman, S. A., Weidlich, S., Knebel, A. and Kulathu, Y. (2017) A single MIU motif of MINDY-1 recognizes K48-linked polyubiquitin chains. EMBO Rep  18 392-402 PMID: 28082312
  • Abdul Rehman, S. A., Kristariyanto, Y. A., Choi, S. Y., Nkosi, P. J., Weidlich, S., Labib, K., Hofmann, K. and Kulathu, Y. (2016) MINDY-1 Is a Member of an Evolutionarily Conserved and Structurally Distinct New Family of Deubiquitinating Enzymes. Mol Cell 63 146-55 PMID: 27292798
  • Kristariyanto, Y. A., Abdul Rehman, S. A., Campbell, D. G., Morrice, N. A., Johnson, C., Toth, R., Kulathu, Y. (2015) K29-selective ubiquitin binding domain reveals structural basis of specificity and heterotypic nature of k29 polyubiquitin Mol Cell 58 83-94 PMID: 25752573
  • Kristariyanto, Y. A., Choi, S. Y., Rehman, S. A., Ritorto, M. S., Campbell, D. G., Morrice, N. A., Toth, R., Kulathu, Y. (2015) Assembly and structure of Lys33-linked polyubiquitin reveals distinct conformations Biochem J 467 345-352 PMID: 25723849
  • Dominika Kwasna, Syed Arif Abdul Rehman, Jayaprakash Natarajan, Stephen Matthews, Ross Madden, Virginia De Cesare, Simone Weidlich, Satpal Virdee, Ivan Ahel, Ian Gibbs-Seymour, Yogesh Kulathu (2018) Discovery and Characterization of ZUFSP/ZUP1, a Distinct Deubiquitinase Class Important for Genome Stability Mol Cell. 70(1) 150-164.e6 PMID: 29576527