University of Dundee


CSC - Structural and membrane biology of polarized trafficking

Membranes and their protein organization are a frontier in our understanding of cell biology. We focus on polarized trafficking as a model to uncover fundamental mechanisms in the organization of structures at membranes. We aim to understand the role of protein complexes including the exocyst. This project seeks to answer mechanistic questions regarding 1) the regulation of protein structural mechanics in polarized trafficking, 2) and the consequences of signaling on this pathway and its organization.

CSC - Intellectual disability in patients with mutations in O-GlcNAc transferase

Intellectual disability (ID) and associated developmental delay are severe neurodevelopmental conditions that affect approximately 1% of the world population. 5% -10% of ID cases are due to mutations in genes located on the X chromosome. One of the genes shown to co-segregate with X-linked intellectual disability (XLID) in twelve patients is the gene ogt. Ogt encodes an essential enzyme, the O-GlcNAc transferase, which catalyses an abundant nucleocytoplasmic post-transcriptional modification O-GlcNAcylation.

CSC - Chemical Structural Biology and Mechanistic Insights into PROTAC Mode of Action

Pioneering discoveries from the Ciulli Laboratory and others have contributed to the establishment of a new modality of chemical intervention into biological system. The new paradigm-shift concept is that of targeting proteins for degradation using small molecules, as an alternative to conventional target blockade or inhibition. Protein degradation can be undertaken by double-headed molecules, also known as PROTACs, that recruit the target for ubiquitin mediated degradation by complexing them with E3 ubiquitin ligases, notably von Hippel-Lindau (VHL) and Cereblon (CRBN), amongst others.

CSC - Molecular mechanisms underlying Parkinson's disease

There is great need for improved understanding of the mechanistic biology underlying Parkinson’s disease. Such knowledge will help with development of new drugs that slow or even halt the progression of the disease. The discovery that hyper-activating mutations in a protein kinase termed LRRK2 causes Parkinson’s, offers the prospect of elaborating new, potentially disease-modifying treatments [1].