Yogesh Kulathu's Research Group

An important role for the ubiquitin system is in the quality control and degradation 
of misfolded and damaged proteins, a process central to maintaining proteostasis. Ubiquitylation also has important non-degradative roles in signalling pathways. One of the ways ubiquitylation is able to mediate such a diverse array of functions is because a range of different ubiquitin signals can be formed. How does the cellular machinery distinguish between different ubiquitin signals to orchestrate a specific response? And what regulatory mechanisms ensure that ubiquitin signals are tightly regulated?

Our lab is interested in understanding (i) how ubiquitylation regulates protein degradation and proteostasis, and (ii) how ubiquitin signalling regulates T-lymphocyte biology and immune responses. To address these fundamental questions, we combine structural, biochemical and genetic approaches to uncover and understand the underlying pathways and mechanisms.

Our research has provided insights into the assembly and recognition of different ubiquitin signals. We recently discovered novel regulators of protein degradation that are highly conserved in evolution. Failure to degrade proteins in a timely manner is the underlying cause 
of diseases such as cancer and neurodegeneration. By studying
 how ubiquitylation regulates protein degradation and proteostasis we hope to better understand the molecular causes of disease that we can exploit for the development of effective therapeutic strategies.

Clockwise from back left: Yogesh Kulathu, Soo Youn Choi, Dominika Kwasna, Matthew McFarland, Joshua Peter, Syed Arif Abdul Rehman, Stephen Matthews, Lee Armstrong, Luuk van den Bekerom,  Sven M Lange, Magdalena Gorka
Clockwise from back left: Yogesh Kulathu, Soo Youn Choi, Dominika Kwasna, Matthew McFarland, Joshua Peter, Syed Arif Abdul Rehman, Stephen Matthews, Lee Armstrong, Luuk van den Bekerom, Sven M Lange, Magdalena Gorka

People

Aimiliani Konstantinou | Visiting 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
Anna Pérez i Ràfols | Postdoctoral Researcher
Joshua Peter | PhD Student
Linnan Shen | Senior Research Technician

Selected Publications

  • Leznicki P and Kulathu Y. (2017) Mechanisms of regulation and diversification of Deubiquitylating enzyme function J Cell Sci doi:10 1242/jcs.201855
  • 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
  • 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
  • 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
  • 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
  • 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