2014 seminars & Events

Archived list of the 2014 seminars & events at the Centre for Discovery Brain Sciences.

January

Evolution and revolution in psychiatry - new ways forward

Thursday 16 January 2014, 12.30pm
Dr Michael Spedding (Spedding Research Solutions)

Reorganisation of striatal connectivity after cocaine exposure

Friday 17 January 2014, 12.30pm
Dr Andrew Macaskill (New York University/ University College London)

Brainstem control of hand function in health after recovery from lesions

Friday 24 January 2014, 12.30pm
Dr Stuart Baker (Institute of Neuroscience, Newcastle University)

Drosphila in the study of Amyotrophic lateral Sclerosis

Friday 31 January 2014, 12.30pm
Dr Guisy Pennetta (Centre for Integrative Physiology)

Germ line stem cells in the human ovary

Friday 31 January 2014, 12.30pm
Professor Evelyn Telfer (Institute of Cell Biology/CIP)

February

Multivesicular release at single GABAergic synapses

Friday 7 February 2014, 12.30pm

Dr Alain Marty (University Paris Descartes)

Abstract: The mechanisms governing vesicular release and postsynaptic signal integration at single synaptic contacts remain poorly understood. Our laboratory has recently developed methods to address these issues at interneuron-interneuron synapses of the cerebellum. Paired recordings of synaptically connected interneurons are obtained, and single synapses are stimulated using either presynaptic action potentials or local calcium uncaging. Functional variations among single synapses mainly reflect differences in their number of vesicular docking sites, with values ranging between 1 and 6. Within a presynaptic varicosity, individual release sites operate independently of each other, giving rise to multivesicular release. Postsynaptically, multivesicular release elicits complex effects including sublinear addition of postsynaptic current, and variations in their time course of decay. Altogether studies on single synaptic contacts reveal unsuspected aspects of synaptic transmission and shed light on the mechanisms of short term synaptic plasticity.

Germ line stem cells in the human ovary

Friday 14 February 2014, 12.30pm
Prof Evelyn Telfer (Institute of Cell Biology/CIP)

Defining spinal pain circuitry

Friday 14 February 2014, 12.30pm
Dr Carole Torsney (Centre for Integrative Physiology)
Exome sequencing strategies in paediatric genetics to identify novel developmental disease genes Friday 28 February 2014, 12.30pm Professor David Fitzpatrick (MRC Human Genetics Unit)

March

Calcium in the heart: from physiology to disease

Friday 7 March 2014, 12.30pm

Prof David Eisner (Institute of Cardiovascular Sciences, University of Manchester)

Abstract: Calcium is the master controller of cardiac function. It needs to increase on each beat to trigger the heart to contract to pump blood. It must fall to low enough levels between beats so that the heart can relax to fill again with blood. Heart disease, the major killer world-wide, is associated with abnormal calcium signaling. It is 130 years since Sydney Ringer found that calcium is required for cardiac contraction. Enormous progress has been made recently in unraveling the regulation of calcium but there is much left to do. In this lecture I will present an overview of cardiac calcium signaling, showing how imaging, electrophysiology, molecular tools and animal models have contributed to our understanding of the physiology. The first half of the talk will concentrate on the simple, yet elegant mechanisms that regulate calcium. The remainder will focus on abnormal calcium regulation and how this can lead to some of the changes seen in heart failure as well as contributing to the origins of cardiac arrhythmias.

Regulation of microRNA biogenesis

Friday 21 March 2014, 12.30pm

Dr Gracjan Michlewski (The Wellcome Trust Centre for Cell Biology)

Abstract: MicroRNAs (miRs) constitute a large family of short (21-23nt), conserved non-coding RNAs. They regulate gene expression by targeting partially complementary sequences in the mRNAs. Each microRNA has the capacity to regulate hundreds of mRNA targets, thus controlling a variety of biological processes, including differentiation, metabolism, neuronal patterning and ageing. In spite of the great effort to understand various biological roles of individual microRNAs, very little has been done to unravel the regulation of their biogenesis. Our group is focused on elucidating the cis and trans-acting factors that play significant roles in microRNA processing and function. A number of mature microRNAs exhibit a tissue-specific pattern of expression, without an apparent tissue-specific pattern for their corresponding primary transcripts (pri-miRs). This discrepancy is suggestive of post-transcriptional regulation of microRNA abundance. Recently, we have demonstrated that the brain-enriched expression of miR-7, which is processed from the ubiquitous pre-mRNA transcript, is supported by inhibition of its biogenesis in non-brain cells. We identified MSI2 and HuR proteins as inhibitors of miR-7 processing in non-neural cells. Our data provide the first insight into the regulation of brain-enriched microRNA processing by defined tissue-specific factors.

Cerebellar ataxia: β-III spectrin’s scaffold of interactions disconnected

Friday 21 March 2014, 12.30pm

Dr Mandy Jackson (Centre for Integrative Physiology)

Abstract: Spectrins are a critical component of the cell membrane skeleton, maintaining cell shape by providing strength and elasticity. They associate with the plasma membrane through protein-protein and protein-lipid interactions. β-III spectrin is present throughout the elaborate dendritic tree of cerebellar Purkinje cells and is required for normal neuronal morphology and cell survival. Spinocerebellar ataxia type 5 (SCA5) and spectrin associated autosomal recessive cerebellar ataxia type 1 (SPARCA1) are human neurodegenerative diseases involving progressive gait ataxia and cerebellar atrophy. Both disorders appear to result from loss of β-III spectrin function. Further elucidation of β-III spectrin function is therefore needed to understand normal physiology and identify possible disease mechanisms. In this seminar I will present some of our recent data using animal models and cell culture systems to address the interplay of various proteins and what effects disruption of these protein complexes has on physiology.

Shocking flies: an invertebrate model for human epilepsy?

Friday 28 March 2014, 12.30pm

Professor Richard Baines (Faculty of Life Sciences, The University of Manchester)

Abstract: There is clinical need to extend understanding of epilepsy and to find novel approaches for treating this condition. Bang-sensitive (bs) Drosophila mutants, which exhibit reduced thresholds for seizure, offer an attractive possibility to combine tractable genetics, electrophysiology and high-throughput screening. We are focussing on two novel aspects of seizure-generation. The first is activity-dependent splicing of the Drosophila voltage-gated sodium channel that increases the persistent current component. Increasing this component promotes action potential firing with acts as a positive feedback to promote further splicing; an effect which left unchecked would likely lead to seizure. The second study shows that manipulation of neuronal activity during embryogenesis can suppress seizure development in bs-mutants or induce seizure in wild type flies. This startling effect suggests that human epilepsy, due to inherited mutations, may be cured by treating the foetus in utero.

May

Role of NMDA receptor in glutamate synapse adaptation: old actor, new vista!

Friday 2 May 2014, 11.30am

Dr Laurent Groc (Interdisciplinary Institute for Neuroscience, Bordeaux)

Abstract: The glutamate NMDA receptors (NMDAR) are central actors for the maturation an plasticity of excitatory synapses. During such adaptive processes, it has been shown that the number and composition of synaptic NMDAR can be rapidly modified. In this lecture, I will discuss our recent studies in which we investigated the cellular pathways by which surface NMDAR subtypes are dynamically regulated during synaptic adaptations, both in physiological networks and in a model of neuropsychiatric disorder. Hosts: Prof David Wyllie/Prof Giles Hardingham
 

Chancellor's fellows symposium

A joint event giving centre members a chance to hear in more depth from the new Chancellors' Fellows in the Centres for Clinical Brain Sciences, Cognitive & Neural Systems, Integrative Physiology and Neuroregeneration.

Thursday the 29th of May, 9:30 - 17:00 Venue: Hugh Robson lecture theatre, George Square.

Chancellor’s fellows all-day symposium

Content

June

Pharmacological enhancement of social behaviour: ecstasy, oxytocin and novel emerging therapeutics

Friday 20 June 2014, 11.30am

Prof. Iain S. McGregor (University of Sydney)

Role of G protein-coupled receptor signalling in diseases of the central nervous system

Friday 27 June 2014, 11.30am

Prof. Stephen Ferguson (Robarts Research Institute, Canada)

 

The Brain - is wider than the sky

The exhibition demonstrates the beauty and complexity of the brain and highlights how neuroscientists at the University of Edinburgh listen to and watch brains in action to improve our understanding of neurological disease.

The Brain - is wider than the sky

 

August

Specification and degeneration of dopaminergic neurons: High-throughput genetics meets C. elegans

Friday 22 August 2014, 11.30am

Dr Maria Doitsidou (University of Stavanger, Norway)

Abstract: My research focuses on investigating the biology of dopaminergic neurons, from the transcriptional programs that regulate their differentiation in development, to the molecular mechanisms that maintain their structural and functional integrity during aging. For this, we use molecular genetic and genomic approaches in C. elegans and bio-samples from human cohorts. We have elucidated the cis-regulatory signature and the corresponding transcription factors that define the terminal identity of the entire dopaminergic system of C. elegans. Using high-throughput screening and next-generation sequencing technologies, we have also identified genetic mutations that cause dopaminergic neurodegeneration and revealed cellular mechanisms of neuroprotection. In collaboration with the Stavanger University Hospital in Norway, we have extended our genetic toolkit to the study of Parkinson’s disease (characterized by the loss of dopaminergic neurons in the substantia nigra), focusing especially on genetic variability and how it impacts on the heterogeneity of disease progression.
Host: Mike Shipston
 

Women in Science

Round-table discussion for female researchers. Female CIP-seminar speakers will talk about their careers and share their experince as women in science.

Speaker: Dr Maria Doitsidou (University of Stavanger, Norway)

Friday, 22nd of Aug 3 pm - 4 pm, venue: Hugh Robson Building, G06

September

Edinburgh-Zhejiang Joint Research Symposium 2014

3rd Edinburgh-Zhejiang Joint Research and Teaching Symposium

Wednesday, 3rd September, 9:00 am, venue: Hugh Robson Lecture theatre

Symposium Chair: Prof. Mark Evans

ZJU Symposium programme

Surprising consequences of mGluR heteromerization

Friday 26 September 2014, 11.30am

Dr Paul J. Kammermeier (University of Rochester Medical Center, Rochester, NY)

Abstract: Metabotropic glutamate receptors (mGluRs) were thought until recently to function mainly as stable homodimers, but recent work suggests that heteromerization is possible. Despite the growth in available compounds targeting mGluRs, little is known about the pharmacological profile of mGluR heterodimers. Here, this question was addressed for the mGluR2/4 heterodimer, examined by coexpressing both receptors in isolated sympathetic neurons from the rat superior cervical ganglion (SCG), a native neuronal system with a null mGluR background. Under conditions that favor mGluR2/4 heterodimer formation, activation of the receptor was not evident with an mGluR2-selective agonist (DCG-IV) or with an mGluR4 selective agonist (L-AP4); however, full activation was apparent when both ligands were applied together, confirming that mGluR dimers re- quire ligand binding in both subunits for full activation. Properties of allosteric modulators were also examined, including the findings that negative allosteric modulators (NAMs) have two binding sites per dimer and that positive allosteric modulators (PAMs) have only a single site per dimer. In addition, a functional interdependence between mGluR1 and 5 was also demonstrated. In neurons co-expressing these receptors, combining a selective mGluR1 competitive antagonist with either an mGluR1 or mGluR5 selective negative allosteric modulator (NAM: BAY36 7620 and MPEP, respectively) strongly occluded signaling by both receptors to an approximately equal degree. By contrast, in cells co-expressing mGluR1 and 2, combining the same mGluR1 competitive inhibitor with an mGluR1 or mGluR2 NAM yielded partial and full inhibition of the response, respectively, as expected for independently acting receptors. In neurons expressing mGluR1 and 5, the selective NAMs each strongly inhibited the response to glutamate, suggesting that these receptors do not interact as heterodimers, which would not be inhibited by selective NAMs. Finally, evidence for a similar mGluR1/5 functional dependence is shown in medium spiny striatal neurons. Together, these data demonstrate cooperative signaling between mGluR1 and 5 in a manner inconsistent with heterodimerization, and thus suggesting an interaction between homodimers.
Host: Ian Duguid

October

Genetics and Epigenetics of Anxiety-Related Behaviour

Friday 3 October 2014, 12.00pm

Prof. Rainer Landgraf (Max Planck Institute of Psychiatry, Munich, Germany)

Abstract: Trait anxiety represents a genetic predisposition that, together with environmental and epigenetic influences, shapes anxiety-related behaviour. CD1 mice selectively inbred for extremes in trait anxiety for >50 generations were used to identify genetic (SNP distribution, expression profiles, copy number variants) and epigenetic (DNA methylation) phenomena underlying anxiety. Combined with behavioural data, these molecular-genetic approaches revealed chromosomal hotspots likely to be involved in trait anxiety regulation. Among them, CRHR1, Glo1, Tmem132D, cathepsin B and vasopressin seem to be the most promising candidate genes. As shown exemplarily with CRHR1, genes differ in their expression profile between high (HAB) and low (LAB) anxiety mice. In addition, CRHR1 is prone to epigenetic regulation. HAB mice, exposed to enriched environment become less anxious, and LAB mice exposed to chronic mild stress become more anxious. This bidirectional shift towards “normal” is associated with changes in (1) CRHR1 expression in the amygdale and (2) network activity at amygdalar level. The transcription factor YinYang1, which may act both as activator and silencer of gene activity, is likely to interact with the CRHR1 promoter to mediate the shifts in gene expression. There is preliminary evidence that epigenetic modifications may at least partially be transmitted to the next generation. In light of the fact that many genes impact on anxiety-related behaviour, each with minor contribution to the phenotype, the translational potential of CRHR1 remains questionable.
Host: Mike Ludwig
 

Women in Science

Round-table discussion for female researchers. Female CIP-seminar speakers will talk about their careers and share their experince as women in science.

Speaker: Dr Dawn Livingstone (CIP, University of Edinburgh)

Friday, 10th October 11am - 12pm, venue: Hugh Robson Building, G06

Steroid A-ring reduction as a modulator of metabolic and inflammatory processes

Friday 10 October 2014, 11.30am

Dr Dawn Livingstone (CIP, University of Edinburgh)

Abstract: Glucocorticoid steroid hormone signalling has potent effects on fuel metabolism and inflammation, and these actions can be modulated by pre-receptor metabolism within target tissues. We are particularly interested in the role of the enzyme 5alpha-reductase 1, which is expressed in metabolically active tissues like liver and fat. Disrupting this enzyme either pharmacologically or genetically results in worsened metabolic risk. Furthermore, the glucocorticoid product of 5alpha-reduction is also active at the glucocorticoid receptor, but results in a different pattern of effects to the parent steroid. We are currently characterising the ways in which these steroids interact with the glucocorticoid receptor, in order to understand the mechanisms underpinning these selective effects and how they may be exploited pharmacologically.

Sex, Flies and No R-R-Red Tape

Friday 10 October 2014, 11.30am

Prof. Richard Ribchester (CIP, University of Edinburgh)

Abstract: I have been studying neuromuscular synaptic development, physiology, plasticity, degeneration, regeneration and pathology in rodent muscle for almost my entire research career but for various compelling scientific and pragmatic reasons I have decided to shift my research model to larval Drosophila. My attention was initially drawn to a reported sexual differentiation of synaptic strength at an identified neuromuscular synapse in 3rd instar larvae. This struck me as a tractable physiological problem of potentially general biological significance, as well as disease relevance since several synaptopathies (including ALS and Alzheimer’s Disease) have sex/gender-risk components. Serendipitously, my attention was also drawn to the potential utility of a new transgenic line, in which myristoylated GCaMP5 is targeted to the inner leaflet of plasma membranes. This effectively constitutes a two-dimensional, postsynaptic fluorescent reporter of synaptic vesicle exocytosis. In addition, it reports large changes in juxtamembrane [Ca2+] during spontaneous and nerve-evoked muscle contraction. This single transgenic tool may therefore prove highly effective for studying mechanisms that link synaptic transmission to excitation-contraction coupling. Coincidentally, I discovered that identified Muscle 5 produces action potentials that bear a remarkable resemblance to mammalian cardiac action potentials. Taken together with optical measurements of excitation-contraction coupling based on GCaMP5 fluorescence, exploration of this observation may yield novel insights into the local cellular control of peristaltic larval contractile waves, and perhaps also provide us an appropriate analogy or new model of sequential contractions of the chambers of the mammalian heart.
Host: Mandy Jackson & Emanuel Busch

Nitric oxide modulation of synaptic release

Friday 17 October 2014, 12.00pm

Dr Joern Steinert (University of Leicester)

Abstract: Abnormal nitric oxide (NO) signalling is implicated in several neurodegenerative diseases but its exact contribution to neuronal death remains elusive due to great complexity of downstream nitrergic targets. Several NO-mediated mechanisms are associated with neuronal degeneration. Elevated NO can lead to formation of cytotoxic peroxynitrite which in turn can directly modulate a wide range of protein functions via nitration of tyrosine-residues (3-Nitrotyrosination [3-NT]). Toxic NO signalling can further alter protein functioning in a process known as S-nitrosylation (S-NO). To date, little is known as to what extent NO-mediated post-translational modifications contribute to or exacerbate neuronal dysfunction. We use glutamatergic synapses (hippocampus and Drosophila neuromuscular junction (NMJ)) as model systems to identify nitrergic signalling pathways to correlate protein modifications with functional changes. During prion pathology at 9 and 12 weeks past prion inoculation, enhanced levels of S-NO and 3-NT were detected shown by immunocytochemistry (ICC). Further, NO application also induced increases in S-NO and 3-NT at the Drosophila NMJ and in order to detect functional effects of these posttranslational modifications, we used two-electrode-voltage-clamp (TEVC) analysis at this synapse. Characterisation of transmission revealed NO-induced changes in transmitter release. NO application moderately affects spontaneous release but strongly reduces evoked release. This is predominantly due to a functional reduction in the size of the vesicle pool available for release without affecting the overall release probability.
Host: Richard Ribchester

Ion channels and pain

Friday 24 October 2014, 12.00pm

Prof. Peter McNaughton (Kings College London)

Abstract: Pain is traditionally regarded as three distinct entities. Acute pain, caused by direct excitation of nociceptive (pain-sensitive) nerve endings, performs the vital function of warning a human or animal of actual or impending damage. Inflammatory pain occurs when inflammatory mediators released by injury enhance the sensitivity of nociceptive nerve terminals, causing a sensation of pain even to normally innocuous stimuli. Inflammatory pain has a protective function but can also be debilitating when prolonged in chronic conditions such as arthritis. Neuropathic pain is caused by nerve damage and has no obvious protective function. Analgesics such as the NSAIDs family are effective against inflammatory pain, albeit with significant side effects, but neuropathic pain is often poorly treated by current analgesics. Ion channels initiate action potentials in nociceptive afferent nerve fibres. They are therefore logical targets for novel pharmaceuticals in the control of pain. The trick will be to block channels important in inflammatory and neuropathic pain, without interfering with the ion channel function which underlies normal acute pain sensation. What are the ion channels important in inflammatory and neuropathic pain, and are these different from ion channels sensing normal acute pain? In a recent study we found that genetically deleting HCN2 pacemaker ion channel in nociceptive neurons abolished the effects of inflammatory mediators such as PGE2 in enhancing neuronal excitability. In vivo we found that inflammatory heat hyperalgesia and neuropathic pain were both abolished. Similar results were obtained with an HCN ion channel blocker. Critically, there was no effect of the deletion or the block on acute pain thresholds. We conclude that HCN2 may be an interesting novel target for the development of analgesics effective in both inflammatory and neuropathic pain. We have initiated a drug development programme which seeks to develop selective HCN2 ion channel blockers as successful novel analgesics free of the side effects of existing treatments. Host: David Wyllie & Carole Torsney
 

Women in Science

Round-table discussion for female researchers. Female CIP-seminar speakers will talk about their careers and share their experince as women in science.

Speaker: Dr Sylvie Schneider-Maunoury (University Pierre and Marie Curie, Paris)

Friday, 31st October 9:30 am - 10:30 pm, venue: Hugh Robson Building, G06

Primary cilia in brain morphogenesis

Friday 31 October 2014, 1.00pm

Dr Sylvie Schneider-Maunoury (University Pierre and Marie Curie, Paris)

Primary cilia are microtubule-based organelles present at the cell surface of most vertebrate cells, whose dysfunctions in humans are responsible for a group of disorders called ciliopathies. The ciliary gene /Ftm/Rpgrip1l /encodes a large scaffolding protein located at the cilium base. Our group has previously shown that /Rpgrip1l /is involved in autosomal recessive ciliopathies with associated brain abnormalities, Meckel and Joubert syndromes (Delous et al., Nature Genetics 2007).Using a mouse mutant line, we have shown that /Rpgrip1l /is required for correct cilium formation in the neuroepithelium and for telencephalic morphogenesis via the formation of the repressor form of the transcription factor Gli3, an effector of Hh signalling (Besse et al., Development 2011). More recently, we have addressed the role of /Rpgrip1l/ in other aspects of telencephalic morphogenesis and in neurogenesis in the cerebral cortex (unpublished data). Our findings, together with data from the literature, allow us to better understand the role of primary cilia in brain morphogenesis and the developmental origin of brain defects found in ciliopathies. Host: Thomas Theil

November

Spacing out: distributed processing of spatial information across hippocampal-prefrontal-parietal networks

Friday 7 November 2014, 1.00pm

Dr Matt Jones (University of Bristol)

The hippocampus contains prize-winning place cells, the parietal cortex contains exquisitely turn-selective neurons and the prefrontal cortex contains all-over-the-place cells. How are these different flavours of spatial code integrated over the course of learning to inform behaviour? I will describe analyses of simultaneous recordings of network activity in rat hippocampus, prefrontal and parietal cortex, highlighting the roles of coordinated oscillations during wake and sleep in binding different features of the cognitive map.
Host: Paul Skehel

 

Of mice and men... Edinburgh Preclinical Imaging facilities

Friday 21 November 2014, 1.00pm

Dr Maurits Jansen & Dr Carmel Moran & Dr Paul Fitch (University of Edinburgh)

The Edinburgh preclinical imaging (EPI) facilities are operated through the College of Medicine and Veterinary Medicine at the University of Edinburgh. They provide state-of-the-art imaging equipment to provide quantitative in vivo, non-invasive imaging of structure and function of all organs and tissues of small animals. In this seminar, Dr Maurits Jansen will present information on high field magnetic resonance imaging (MRI); Dr Carmel Moran on high resolution ultrasound imaging and Dr Paul Fitch on high sensitivity optical imaging techniques. Dr Maurits Jansen: High field magnetic resonance imaging for preclinical applications Dr Carmel Moran: Of mice and men - ultrasound imaging for preclinical applications Dr Paul Fitch: Optical imaging techniques for preclinical applications. Host: Mandy Jackson & Emmanuel Busch
 

Patrick Wild Centre Supporters’ Day

The afternoon will begin with a short presentation on the highlights of the past year. This will be followed with refreshments where you will have the opportunity to ask questions and share your thoughts about the Centre with us.

Monday 24th November 2014, 2:30pm - 4pm venue: Informatics Forum , 10 Crichton Street Edinburgh EH8 9AB

Patrick Wild Centre

Beyond Pretty Pictures - Optical Imaging in the College of Medicine and Veterinary Medicine

Friday 28 November 2014, 1.00pm

Dr Rolly Wiegand (CIP, University of Edinburgh)

Light microscopy is the most widely used imaging modality in biomedical research and provides scientists with a rapidly developing ‘experimental tool kit’ for basic and biomedical research. This talk will summarise some of the advanced technologies, central imaging services and related infrastructure available in different areas of the CMVM. The recent multi-million pound investment into optical imaging facilities in the CMVM has put Edinburgh University at the forefront of advanced light microscopy. An overview will highlight these new developments and provide a guide to microscopy-related facilities across the CMVM, focussing on services and technologies outside the Central area.
Host: Mandy Jackson & Emanuel Busch

A grid cell grid

Thursday 4 December 2014, 12.30pm

Prof. Michael Brecht (Humboldt University Berlin, Germany)

Extracellular recordings have provided detailed phenomenology of spatial discharge patterns (place cells, grid cells, head direction cells) in the rodent brain. At the same time we know very little about the underlying microcircuits because extracellular recordings do not identify to recorded cellular elements. We devised methods that allow the identification of neurons in freely moving animals, which we apply the rodent entorhinal cortex. We reference cells relative to the patchy architecture of layer 2 in medial entorhinal cortex. Anatomical analysis reveals that calbindin-positive pyramidal neurons layer 2 in medial entorhinal cortex are arranged in a regular and often hexonal grid. Across animals this grid of patches shows a consistent alignment to the parasubiculum, cholinergic inputs and the layer 1 axons also run along a grid axis. I will provide evidence that grid cells correspond largely to these calbindin-positive pyramidal neurons in layer 2. I conclude that layer 2 grid discharges originate in a spatiotemporally highly organized microcircuit, a pyramidal ‘grid-cell-grid.
Host: Matt Nolan
[scald=1029:sdl_editor_representation {"alt":"BiochemSoc logo","caption":""}]

 

**The 2014 Biochemical Society Morton Lecture** A fast Endophilin-dependent, Clathrin-independent endocytic mechanism

Friday 5 December 2014, 1.00pm

Prof. Harvey McMahon (MRC Laboratory of Molecular Biology, Cambridge)

Cell shape is adapted to function. Organelle shape and local membrane architectures are likewise optimised for the processes that take place on and within these microenvironments. We focus on the dynamic regulation of membrane shape, which can occur by the interplay between the transient and regulated insertion of membrane bending motifs and the detection and stabilisation of membrane shape. This approach has allowed us not only to describe the biophysics of membrane shape changes but also to take a fresh look at membrane dynamics in physiological processes like exocytosis and endocytosis. In doing so we have noted that proteins with amphipathic helices or hydrophobic membrane-inserting loops are likely to effect or respond to curvature and that the membrane interaction surfaces of proteins can sense shape (like proteins of the BAR Superfamily). This molecular view has allowed us to ascribe novel cell-biological functions to proteins (e.g. the mechanistic affect of synaptotagmin in membrane fusion) and to give a more insightful view of how these processes work. Thus we can now go from the biophysics of a molecule, to better understanding of known pathways and to the molecular characterisation of novel cellular trafficking pathways both of endocytosis and exocytosis. I will present one such novel pathway that we are in the midst of characterising. It is a ubiquitous pathway operating especially in synapses but also in all cell types we have tested. It is clathrin-independent and dynamin dependent and operates at a much faster timescale that clathrin vesicle formation. We believe that a molecular understanding of this pathway will lead to fresh insights into fast membrane trafficking responses, like synaptic vesicle retrieval.
Host: Mike Cousin