University of Dundee

Protein Modification

Potential Supervisors within this theme

Prof Geoff Barton

Bioinformatics is the research field that seeks to find computational ways of understanding biological systems. The subject is very broad and ranges from research in statistics and computer science, through software engineering and database development, to applications in specific biological systems. The possible biological applications are equally broad, from the study of populations through molecular structure and interactions, to simulations of metabolic and signalling processes. Our work draws on and contributes to computer science, software engineering and statistics on one side and many aspects of modern biological research on the other.  We publish our work both in conventional journals and as software packages and on-line resources accessible from our website: www.compbio.dundee.ac.uk.

Prof Mark Field

Parasitic diseases caused by protozoa constitute a major global threat. Our work melds several key aspects of protist biology, principally focusing on the parasitic organisms of the trypanosome group. Principle research objectives are the discovery, functional characterisation and validation of novel gene products, drug targets and chemical tools towards neglected diseases to provide therapy, deep insights into protist cell biology and to understand eukaryotic evolution at the molecular level. The laboratory focuses on understanding how surface proteins are regulated, targeted and turned over and in particular how these processes connect with sensitivity towards drug mode of action.

Prof Ron Hay

Specificity in the SUMO system appears to be achieved by modification of large groups of proteins by a PIAS E3 ligase mediated SUMO spray. Our aim is to define the mechanism by which PIAS E3 ligases select multiprotein complexes for modification. Proteomic identification of sites of SUMO modification and SUMO ChIPSeq analysis provide evidence that the SUMO spray functions in human induced pluripotent stem cells. Our objectives are to establish the role of the “SUMO spray” in maintaining pluripotency. We will deplete SUMO globally, at specific genomic loci and at multiprotein complexes. Changes in cell fate, histone marks, chromatin accessibility, transcriptional output and the stability of multiprotein complexes will be followed. PIAS proteins can be recruited to substrates via DNA, SUMO and specific protein interactions. We will use structural, biochemical and single molecule approaches to reveal the mechanism of SUMO spray mediated substrate modification. 

 

Dr Piers Hemsley

S-acylation is the post-translational addition of fatty acids to protein cysteine residues though a thioester bond. Importantly, and unlike other lipid modifications such as myristoyation, farnesylation and geranylgeranylation, S-acylation is reversible in a rapid and regulated manner. This enables S-acylation to act as a molecular switch for controlling protein function, activation state, trafficking, turnover, conformation and interaction with other proteins. A particular feature of S-acylation is its ability to increase association of proteins with membranes; every S-acyl group added provides a membrane anchoring strength equivalent to one transmembrane domain. This is very important for attaching otherwise soluble proteins to membrane. Interestingly, integral membrane proteins make up over 50% of the known S-acylated proteome indicating that membrane anchoring is not the primary role of S-acylation in many circumstances. S-acylated proteins are found in every membrane bound sub-cellular compartment studied to date including the nucleus.

Prof Miratul Muqit

Mutations in PTEN-induced kinase 1 (PINK1) lead to autosomal recessive Parkinson’s disease. PINK1 is unique amongst all protein kinases since it contains a mitochondrial targeting domain and also three loop insertions within its catalytic domain. My laboratory is utilizing state of the art biochemical, proteomic, transgenic and structural methodologies to address the next major questions for understanding the PINK1 signaling pathway. We wish to understand in more detail how PINK1 activity is regulated by mitochondrial depolarization and identify novel regulatory molecules of PINK1 activity.

Dr Frederico Pelisch

Our lab focuses on understanding the molecular mechanisms that guarantee proper chromosome segregation during female meiosis. We are interested in how post-translational modifications participate in this process through regulated assembly of protein complexes. To achieve this, we use a combination of cell biology, biochemistry, and proteomics. 

Dr Andrei Pisliakov

Proteins in a living cell act as molecular machines that carry out specific functions, e.g. catalyse biochemical reactions, move ligands across biological membranes, mediate signalling, etc. The overall goal of our research is to understand the biomolecular function and underlying mechanisms of proteins by using the (physics-based) modelling and simulation methods. The work is done in close collaboration with our experimental colleagues, with occasional applications in drug discovery. Our current work focusses on (i) allosteric regulation of enzymes that control regulated gene expression; (ii) effects of post-translational modifications on protein-protein interactions; (iii) proton transfer processes in membrane proteins

Prof Daan van Aalten

Ogt encodes an essential enzyme, the O-GlcNAc transferase, that catalyses an abundant nucleocytoplasmic post-transcriptional modification called O-GlcNAcylation and is mutated in several families with intellectual disability. In the van Aalten lab we use a wide range  of techniques to study the effects of these mutations,  ranging from chemical biology, biochemistry, molecular biology, cell biology and genetics, in stem cells, flies and mice. The aim of the lab is to uncover the links between O-GlcNAcylation and the patient phenotypes and explore pharmaceutical/genetic approaches to treating these