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Accueil > Départements > Biologie Cellulaire > Christien MERRIFIELD : Dynamique du Cytosquelette et Traffic Membranaire

Christien MERRIFIELD : In memoriam

Christien J Merrifield
Christien J Merrifield

It is with deep sadness that we announce the abrupt passing of Christien Merrifield on October 29, 2017.
Christien Merrifield, who grew up on the Isle of Wight in England, was a brilliant student at Oxford University before receiving his PhD from University College London in 1999. Once at Oregon and Yale University, as a postdoctoral fellow, he became rapidly a world-class leader in his field, which gave him the opportunity to join the prestigious Laboratory of Molecular Biology in Cambridge as a group leader in 2004. We had the privilege of having him join our campus as a group leader and CNRS Research Director in 2012.
Christien Merrifield pioneered the use of evanescent field microscopy to reveal the dynamics of clathrin-mediated endocytosis, a mechanism allowing cells to internalise essential molecules from the extracellular medium. His breakthrough findings inspired many other prominent researchers in his field and paved the way to understand the molecular mechanisms underlying clathrin-mediated endocytosis. Several articles published by Christien Merrifield are now considered as classics in cell biology and have won him the admiration of scientists all over the world. Recently, he wanted his research to make an impact on major public health problems such as muscle diseases and diabetes.
Christien Merrifield leaves behind a major contribution to life sciences. Those who had the chance to know him will miss his enthusiastic creativity, his undeniable work ethics, his engaging personality and his subtle British sense of humour.
The I2BC would like to express his sincere condolences to Christien’s colleagues, friends and family.

Dynamique du Cytosquelette et Traffic Membranaire
The plasma membrane defines the surface of a cell and receptors - which are specialized proteins floating in the plasma membrane lipid bilayer - convey messages inside the cell to tell it to move, change shape, stick to neighbouring cells, divide or die. In order to regulate receptor signalling it is clearly important that cells carefully control the concentration of receptors in the plasma membrane and indeed the dysregulation of receptor trafficking underlies many disease states. Our lab is interested in the mechanism of endocytosis by which cells remove receptors from the plasma membrane. In one the most important types of endocytosis - referred to as clathrin mediated endocytosis - the endocytic machinery concentrates receptors into specialized patches which curve into 100nm membrane vesicles, coated with clathrin, which pinch off into the cell interior. To better understand the molecular choreography of clathrin mediated endocytosis we pioneered specialized imaging techniques using multi-colour total internal reflection fluorescence microscopy (TIRFM) to detect individual endocytic events in living cells while simultaneously measuring the arrival and departure of endocytic proteins (Merrifield et al., 2005). This allowed us to map out the molecular choreography of clathrin mediated endocytosis (Taylor et al., 2011) and to probe functional links between specific endocytic components (Taylor et al., 2012).

More recently we have adapted our experimental system to image single ligand-triggered endocytic events of medically relevant G-protein coupled receptors (GPCRs, such as beta-1-adrenergic receptor, Fig1) and receptor tyrosine kinases (RTKs) such as epidermal growth factor receptor (EGFr) at the level of single endocytic scission events in real time in living cells (Lampe et al., 2014). Using these highly sensitive and quantitative imaging techniques in combination with cell, molecular and biochemical techniques we are addressing the role played by the cytoskeleton in both constitutive and ligand-triggered endocytosis and the role played by the scission reaction itself in post-translational receptor modification and the signalling events conveyed by receptor cargos.

Fig1. Beta-1-adrenergic receptor internalizes through coated pits.
A. HEK-293 cell imaged using TIRF microscopy and expressing phluorin-beta-1-adrenergic receptor at pH7.4 (green, left panel) and 2s later at pH 5.2 (middle panel). Newly endocytosed vesicles appear as bright green spots at pH 5.2 colocalized with coated pits labelled with Mu2-mCherry (hollow arrows, right panel). Some vesicles uncoat but briefly remain close to the plasma membrane (solid arrows). B. Example scission event (upper panels, black arrow) and quantified fluorescence (lower graphs) showing phluorin-beta-1-adrenergic receptor signal at a coated pit at pH 7.4 (BAR7), pH 5.2 (BAR5) and Mu2-mCherry at pH 5.2 (Mu2-mCh). C. Time aligned and averaged fluorescence traces for a cohort of 500(+) events.


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