Ubiquitin signalling, which involves the posttranslational modification (PTM) of proteins with ubiquitin, regulates almost every aspect of eukaryotic biology. This versatility is possible because proteins can be modified with different types of ubiquitin codes resulting in distinct functional outcomes. An indispensable role for ubiquitylation is to serve as a signal for the degradation of misfolded and damaged proteins. In addition to degradation, ubiquitin modifications can serve as distinct signals to facilitate intracellular communication. The cellular machinery therefore has to read the different ubiquitin codes in order to ensure that the appropriate response is produced. Further, these codes have to be erased once the functional outcome is produced, a process carried out by a class of enzymes known as Deubiquitinases. In the lab we study these processes, using a range of techniques including biochemical approaches, proteomics, structural biology and mouse models to elucidate new layers of control in protein degradation. This research is fundamental to our understanding of cell biology in health, and is important, as failures in protein degradation underly many diseases especially age-related diseases such as Alzheimer’s and Parkinson’s disease.
We are looking for an enthusiastic student to join the group to study how protein degradation is regulated by the ubiquitin system. Your PhD will build upon tools, reagents and models we have recently established in the lab. Working on an independent project, you will have the opportunity to learn and apply different approaches ranging from biochemistry, cell biology, genetic screens and state-of-the-art proteomics methods to understand at the molecular level how aberrant proteins are degraded, the ubiquitin signals involved, how they are decoded and how this process is regulated. This project will provide the opportunity to improve our understanding of one of the most fundamental processes in the cell.
1. Kwasna D, et al. (2018) “Discovery and characterization of ZUFSP, a novel DUB class important for genome stability”. Molecular Cell. 70(1):150-164.
2. Kristariyanto YA, et al. “A single MIU motif of MINDY-1 recognizes K48-linked polyubiquitin chains”. EMBO Reports 18 (3): 392-402
3. Kristariyanto YA, et al. (2015) “K29-selective ubiquitin binding domain reveals structural basis of specificity and heterotypic nature of K29 polyubiquitin”. Molecular Cell 58(1): 83-94