I graduated with an Honours degree in Pharmacology from the University of Edinburgh in 1979 and moved to Birmingham to work in the Department of Medicine with Professors Michael Sheppard and Steve Franks. My research focused on the effects of neurotensin on the hypothalamo-pituitary-thyroid axis and I was awarded a PhD for this work in 1985. Post-doctoral research work with Professor Kevin Docherty, also in Birmingham, maintained my interest in endocrinology, though I became more interested in the biosynthesis of polypeptide hormones, particularly insulin, and their mechanism of targeting into secretory granules. I was appointed to a Lectureship in Aberdeen University in 1994 and promoted to Senior Lecturer in 2003.
Biosynthesis of polypeptide hormones
As a post-doc in Professor Docherty's lab I used a novel in vitro translation system derived from Xenopus laevii eggs to characterise the activity and biosynthesis of the newly identified prohormone convertases PC2 and PC2. These long sought after enzymes are responsible for the proteolytic cleavage of prohormones to their active form and my work was the first to characterise their enzymatic activity. Following this my interest turned to how these enzymes could be targeted into secretory granules along with the prohormones they act on.
Targeting of proteins within neuroendocrine cells
Neuroendocrine cells, such as pancreatic ß-cells, have two separate pathways for proteins to exit the cell; the constitutive secretory pathway (which is common to all cell types and allows for the continuous release of proteins to the cell surface) and the regulated secretory pathway (which is specific to neuroendocrine cells and allows for the storage of large amounts of proteins for secretion in response to a specific stimulus). My group were interested in the mechanism a cell uses to direct proteins into the regulated secretory pathway. Using the prohormone convertase PC2 as a model regulated secretory protein, we identified a region at the N-terminus of the protein which encodes a transferable, dominant membrane-association signal. Membrane association is thought to be an important step in the process of targeting to the regulated secretory pathway. We also showed that this membrane association occurs by an interaction with the lipid bilayer, rather than with any protein component of the membrane. More specifically, PC2 interacts with membrane microdomains known as lipid rafts. These areas of the membrane are enriched in cholesterol and sphingolipids and have previously been shown to be important for an analogous sorting event, that of sorting to the apical membrane of polarised epithelial cells. Several proteins destined for the regulated secretory pathway have now been shown to associate with lipid rafts, including the prohormone convertase PC3, carboxypeptidase E and thyroglobulin. It is, therefore, hypothesed that lipid rafts play a part in sorting to the regulated secretory pathway but the mechanism involved is unclear.
Involvement of lipid rafts in protein sorting and secretion
Lipid rafts have proposed roles in diverse cell processes, including cell signalling, mediating front-rear polarity in migrating cells, exocytosis, GLUT4 translocation and protein targeting. Since lipid rafts underpin many fundamental processes in the eukaryotic cell it is clear that the vast array of functions proposed for them must be dependent on their association with particular proteins, some of which will play a regulatory role either in lipid raft formation or in their downstream function. Identification of such proteins will be an important step in our understanding of lipid raft function. A family of proteins that associate with lipid rafts has been identified and the original member of this family, MAL, has a proposed role in raft-mediated protein targeting in epithelial cells. My group identified a new member of this family, MAL2 (also simultaneously identified by other groups and called TPD52 and CRHSP28) that has a more ubiquitous distribution. A study of this protein and its interactions with other cytoplasmic proteins will further our understanding of lipid raft formation and raft-mediated protein targeting.
My time is now split between my role as Director of Studies, Admissions (Science), a 0.75 FTE role, and my role as a member of the School of Medical Sciences (0.25 FTE). I have a major interest in teaching and enhancing the quality of teaching within the Institute, the latter of which I achieve through my roles as Convenor of the University's Quality Assurance Committee and Institutional Team leader for the Quality Assurance Agency's Developing & Supporting the Curriculum Enhancement Theme. My personal interests are in using innovative teaching techniques and interactive lecture formats. In 2011 I was awarded a student-led teaching award for "Teaching for Employability".
QAA (Scotland) Enhancement Theme Conference (2014) presentation.
An overview of the work that Aberdeen University carried out during the Developing & Supporting the Curriculum Enhancement Theme was presented at their Annual Conference in June 2014. The full Prezi can be viewed at http://prezi.com/ldmticz4tlnn/?utm_campaign=share&utm_medium=copy&rc=ex0share and contains links to the various projects undertaken during the theme. Many thanks to Pat Bain for the illustrations and Phil Marston for advice on making the Prezi.
Course Coordinator for BI25M7 (Energy for Life)
Contribute to teaching on:
BI25M7 (Energy for Life, level 2 course) - lectures on metabolic regulation and revision lectures
MB3006 (Molecular Biology of the Cell, level 3 course) - lectures on eukaryotic transcription and protein sorting
SM3001 (Frontiers in Molecular Medical Sciences, level 3 course) - lectures on protein:protein interactions
MB4050 (Advanced Molecular Biology, level 4 course) - lectures on eukaryotic secretory pathway
MB4505 (Honours Molecular Biology B, level 4 course) - research tutorial on non-classical secretory pathways
- Further Info
Member of QAA (Scotland) 'Developing & Supporting the Curriculum' Enhancement Theme Steering Group
Member of the North East Scotland College Joint Liaison Group
Member of the Dundee and Angus College Joint Liaison Group
Director of Studies, Admissions (Science) - 0.75FTE - responsible for the recruitment of students into all of the University of Aberdeen's undergraduate BSc programmes.
Convenor of the Students' Progress Committee, Science
Convenor of the Quality Assurance Committee
Member of the Senate Business Committee
Member of the University Committee for Teaching & Learning
Chair of the 'Developing and Supporting the Curriculum' Enhancement theme Institutional team
Ex officio member of Senate
Member of the Univeristy of Aberdeen Career Mentoring Programme Advisory Group