Colin Rickman

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Research interests

Molecular Analysis of Eukaryotic Membrane Secretion 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. 1. 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. Figure 1. Super-resolution microscopy of SNAREs. Standard resolution microscopy of the base of a secretory cell (left). The region highlighted is shown using the PALM technique revealing the position of individual SNARE proteins (right). 2. SNARE Protein Regulators In neuronal and neuroendocrine cells, the release of cargo is highly regulated. We are interested in how SNARE accessory proteins (synaptotagmin, complexin, munc18 NSF and small GTPases) can regulate this process from the single molecule to the system-wide level. We are investigating the role of these proteins both in vitro, using highly purified protein components, and also in a cellular environment using advanced microscopic techniques. Many of these investigations utilise Förster resonance energy transfer (FRET) to report with high spatial sensitivity changes in protein interactions and conformations. Through these studies we aim to uncover the impact of these accessory proteins on SNARE protein interactions and the process of membrane fusion. Figure 2. Model of SNARE and accessory protein interactions preceding membrane fusion.
  1. E-pub ahead of print
  2. Published

    Smart-aggregation imaging for single molecule localisation with SPAD cameras

    Research output: Contribution to journalArticle

  3. Published

    Automated single particle detection and tracking for large microscopy datasets

    Research output: Contribution to journalArticle

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Frequent Journals

  1. Journal of Biological Chemistry

    ISSNs: 0021-9258

    Additional searchable ISSN (Electronic): 1083-351X

    American Society for Biochemistry and Molecular Biology Inc.

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  2. Biochemical Journal

    ISSNs: 0264-6021

    Additional searchable ISSN (Electronic): 1470-8728

    Portland Press Ltd.

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  3. Cellular and Molecular Neurobiology

    ISSNs: 0272-4340

    Additional searchable ISSN (Electronic): 1573-6830

    Springer New York

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  4. EMBO Reports

    ISSNs: 1469-221X

    Additional searchable ISSN (Electronic): 1469-3178

    Nature Publishing Group

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  5. Nature Communications

    ISSNs: 2041-1723

    Additional searchable ISSN (Electronic): 2041-1723

    Nature Publishing Group

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  1. Journal of Neurochemistry (Journal)

    Activity: Publication peer-review and editorial workPublication peer-review

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ID: 9813