Dr Colin Rickman

Lecturer

+44 131 4514193

c.rickman@hw.ac.uk


WP2.03

Heriot-Watt University

Edinburgh

EH14 4AS

http://www.lifescienceinterface.hw.ac.uk

Biography


Dr Colin Rickman has worked in the field of membrane trafficking and fusion for the last ten years. Over this period he has published a number of research papers in high ranking journals on the protein interactions underlying regulated membrane fusion in endocrine and neuronal regulated fusion. During his doctoral training and subsequent postdoctoral position (MRC Laboratory of Molecular Biology, Cambridge) he applied a broad range of protein biochemistry techniques to describe a cascade of protein-protein interactions regulating multiple steps of the fusion process. To expand on this in vitro based understanding of regulated membrane fusion, Rickman joined Rory Duncan's research group as a postdoctoral researcher to apply protein biochemical approaches to fluorescence imaging in living cells. Colin is an expert on fluorescence microscopy acquisition and analysis of plasma membrane proteins. He is now establishing his own research group concentrating on the organisation of proteins at the single molecule level using super-resolution microscopy supported by funding from Heriot-Watt University(core-funding), the Wellcome Trust, the MRC and the Royal Society. As a core-funded lecturer in the Life-Physical Sciences Interface at Heriot-Watt University he has established key collaborations with physicists and mathematicians to provide inventive routes for data acquisition and analysis.

Projects


The process of secretion (or exocytosis) involves the fusion of cargo-containing vesicles with the plasma membrane and is a fundamental property of all eukaryotic cells. In higher organisms this mechanism has evolved to provide the highly regulated release of neurotransmitters in the brain and hormones such as adrenaline and insulin. This process is targeted by many toxins, including clostridial neurotoxins, and is also deficient in a number of disease states. Our research is focused on understanding at the molecular level how this highly orchestrated process operates and what happens when this process goes wrong.


Spatial Organisation of the Fusion Machinery


The process of membrane fusion is catalysed by the SNARE proteins. This highly conserved protein family mediates the fusion of membrane-bound compartments in all eukaryotic cells. These proteins have been proposed to provide the energy to drive membrane merger in the final steps of membrane fusion. In humans, regulated secretion occurs in highly specialised regions of cells, epitomised by the localised fusion of synaptic vesicles at the active zone of a synapse. We are investigating the spatial organisation of the SNARE fusion machinery from the whole cell to the single molecule level. To examine this we are using advanced optical bio-imaging techniques including the super-resolution PALM technique, which allows the observation of thousands of single proteins at the plasma membrane. By examining the SNAREs and other components of the release machinery (ion channels and accessory proteins) we aim to generate a molecular map of these proteins and uncover the determinants of their spatial organisation.


(In collaboration with Rory Duncan, Weiping Lu and Gabriel Lord. Funded by the Royal Society)


Real time analysis of SNARE protein dynamics during exocytosis


The SNARE proteins are essential for secretion, and so normal physiology. Unfortunately, the techniques required to analyse the function of proteins at the molecular level in living samples have been severely limited until recently, so our understanding of their functions, locations and dynamic interactions remains limited. This project will address these questions, analysing SNARE protein molecular dynamics in living neurons. A combination of quantitative in vitro biochemistry and advanced imaging approaches will tell us how the proteins’ functions are regulated by calcium, in real time, with high spatial accuracy.


(In collaboration with Rory Duncan and Luke Chamberlain (Strathclyde). Funded by the Medical Research Council)


Molecular spatio-temporal dynamics of neuronal Sec-1


nSec-1, also known as Munc18-1, is one of only 4 proteins absolutely essential for secretion in cells. As secretion is central to normal physiology (for example, it is faulty in diabetes, schizophrenia, epilepsy etc), understanding how these proteins work is a key aim. Biochemists have told us about the proteins involved in secretion and their interactions, but the ‘wheres’ and ‘whens’ of the actions of these molecular machines in cells remain largely speculative. This project will determine where munc18 acts in a living cell, where and when it interacts with its binding partners, how it is distributed, and how this is regulated, all at the level of single molecules in living cells.


(In collaboration with Rory Duncan. Funded by the Wellcome Trust)


Secretory Vesicles


This project utilises novel imaging approaches being developed by Professor Alan Greenaway, to increase the rate of acquisition of 3-D stacks using a widefield microscope. This is important, because our present acquisition rate, of approximately 1 entire cell stack per second, is too slow to permit accurate tracking of fast-moving organelles. By using Alan’s novel optical techniques, we can increase the rate 3, 6 or perhaps even 9-fold - this will permit real-time, 4-dimensional analyses of live-cell dynamics.


(In collaboration with Alan Greenaway and Rory Duncan. Funded by the STFC)

Group Members


Dr Kirsty Martin

Deirdre Kavanagh

Charlotte Hamilton

Katia Hiersemenzel

Alicja Graczyk

Robert Ferguson