Supervisor Project : Understanding the complexity of polyUb signaling in mitophagy and proteostasis.

Partner Lab


The MRC Protein Phosphorylation and Ubiquitylation Unit (PPU) at the University of Dundee is a world class research institute, in which researchers make use of cutting-edge technology to study cellular and molecular mechanisms that underpin a number of diseases such as neurological disorders, cancer and hypertension. Scientists at the MRC PPU tackle major long-term questions, with a focus on the regulation of eukaryotic cell biology and human disease by protein phosphorylation and ubiquitylation. The MRC PPU operates as a focal point between leading life scientists, pharmaceutical companies and clinicians, to get a deeper understanding of diseases and how to treat them. The MRC PPU is part of the the School of Life Sciences (SLS) of the University of Dundee (UNIVDUN) and therefore benefits from having both a university and research institute environment. The SLS is repeatedly voted one of 'the best places for a life scientist to work' by The Scientist magazine.
Webpage: https://www.ppu.mrc.ac.uk/research/principal-investigator/yogesh-kulathu


The main goals of Yogesh Kulathu’s lab at the MRC PPU are to understand how ubiquitylation regulates protein degradation and proteostasis. He obtained his PhD at the Max Planck Institute for Immunobiology and University of Freiburg, and he did his postdoctoral training at the MRC Laboratory of Molecular Biology, Cambridge. Research in his lab is mainly funded by the MRC and an ERC Starting grant. Yogesh is an EMBO Young Investigator and Lister Prize Research Fellow.

Summary of the Project

Polyubiquitin chains have important roles in targeting proteins for degradation and also have important signalling roles in processes such as mitophagy. Different types of polyubiquitin signals are assembled in different settings and produce distinct outcomes. Recent research has revealed that the ubiquitin signal is more complicated than previously anticipated with polyubiquitin chains of complex architectures being used. It is therefore an immense task for the cellular machinery to tell the difference between all the different types of polyubiquitin modifications, and the underlying mechanisms are not well understood. The goal of this project is to address how ubiquitin signals of complex topologies are assembled and decoded to produce distinct outcomes. A second aim is to define the topology of ubiquitin signals of complex architectures using recently developed tools and methods to study polyubiquitin. By employing a combination of biochemical, proteomic and genetic approaches, this research will reveal fundamental insights not only into ubiquitin signalling, but also how proteins and defective mitochondria are targeted for degradation.