Hautbergue, Guillaume - University of Sheffield

个人简介

Faculty Lecturer in Translational Neuroscience December 2012 - present Dr Hautbergue was recruited to the Sheffield Institute for Translational Neuroscience in August 2012 to set up the laboratory of RNA Molecular Biology, which is aimed at understanding the cause of gene expression dysregulation in neurodegenerative diseases such as ALS/MND and SMA in order to develop novel strategies of neuro-protective therapies. Senior Experimental Officer March 2010 – November 2012 (i) Department of Neuroscience, SITraN, University of Sheffield, U.K. August – November 2012 Setting up the RNA biology laboratory and my research group in SITraN to apply my scientific skills in RNA biology research to the understanding of RNA processing dysregulation in ALS/MND. (ii) Department of Molecular Biology and Biotechnology, University of Sheffield, U.K. March 2010 – July 2012 Structural and molecular mechanisms of human and viral mRNA nuclear export. Characterisation of ribonucleo-protein complexes. Expression, purification and solubility of proteins. Supervision of students/staff from other laboratories across Faculties. Module coordinator of undergraduate level 2 practical classes (MBB220, MBB226). Post-Doctoral Research Associate January 2002 – February 2010 Department of Molecular Biology and Biotechnology, University of Sheffield, and Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology, U.K. Principal Investigator: Prof Stuart A. Wilson The development of a general method to solubilise proteins led to the structure/function analysis of known and uncharacterised mRNA export adaptors establishing the presently accepted model for the molecular mechanisms of human mRNA nuclear export. Ph.D. of Molecular and Cellular Biology (Very Best Commendation with Honour) Université Pierre et Marie Curie Paris VI, Paris, France. August 1997 – September 2001 Department of Biochemistry and Molecular Genetics, Commissariat à l'Energie Atomique, Saclay, and Laboratory of Molecular Genetics, CNRS URA-1302, Ecole Normale Supérieure, Paris, France. Principal Investigator: Dr Valérie Goguel Function of the yeast CTD Kinase I and atypical ubiquitin-mediated regulation of its activity. French National Service October 1996 – July 1997 Sergeant (“Maréchal des Logis”) of the French Ground Armed Material Forces. Lead management training, First Help Training Certificate – Awarded a French National Defence bronze medal. Molecular and Cellular Biology Advanced Studies Diploma June 1996 Université Pierre et Marie Curie Paris VI, Paris, France. Ranked in the top 3 for a Ph.D. fellowship. M.Sc. Biochemistry (With Distinction) June 1995 Université Denis Diderot Paris VII, Paris, France. Biochemistry Higher Technological Certificate (Best Commendation) June 1993 Ecole Nationale de Chimie Physique Biologie (ENCPB), Paris, France. First National Prize in Biochemistry June 1990 France and French Overseas Countries in the competitive examination "Concours Général" Biochemistry Baccalauréat (Best Commendation) June 1990 Lycée Pierre et Marie Curie, Sens, France

研究领域

Our research focuses on identifying pathophysiological consequences of widespread RNA dysregulation in neurodegeneration in order to design, develop and test novel strategies of neuroprotective therapies. Widespread dysregulation of the RNA metabolism has been recognised as a key pathophysiological component causing at least four neurodegenerative disorders: motor neurone disease (MND), also called Amyotrophic Lateral Sclerosis (ALS), spinal muscular atrophy (SMA), Huntington’s disease (HD) and spinocerebellar ataxias (SCAs). Widespread alteration of the transcriptome has also been reported in normal ageing of the brain and many neurodegenerative disorders are late progressive adult-onset diseases. Neurodegeneration in Parkinson’s disease (PD) or Alzheimer’s disease (AD) is also likely to exhibit and/or involve broad alteration of the RNA metabolism and of multiple biological processes. Although some genetic causes of these often-fatal diseases are known, the multifactorial molecular mechanisms governing pathogenesis and progression are still poorly understood. Genome-wide studies from cell or animal models and human brains extensively described large alterations of transcriptomes at all levels of the RNA metabolism including mRNA/miRNA biogenesis and processing, axonal transport and translation of mRNA. Thousands of changes were reported in multiple cellular pathways with dysregulation reaching up to one third of the TDP-43 linked MND transcriptome. Since it is not feasible to investigate all individual changes, it is impossible to distinguish alterations that are causing neurodegeneration from those which are consequences of initial alterations – a bottleneck in the identification of gene expression-modifying therapies. In fact, the functional outcomes of widespread RNA dysregulation in neurodegeneration and ageing remain uncharacterised at the protein levels, which are ultimately linked to neuron survival or death. Beyond our investigation of altered RNA/protein expression levels and the development of neuroprotective strategies, we also aim at answering challenging scientific questions concerning RNA dysregulation in neurodegeneration and ageing: Proportion and identities of abnormally processed RNA molecules that escape the safeguarding mechanisms of nuclear retention? Which abnormal proteins, sequences and numbers, get synthesised from incorrectly processed mRNAs? Roles of long intergenic non-coding (linc) RNAs that exhibit similar features to protein-coding genes?

近期论文

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Dr Guillaume Hautbergue has an excellent track record of publications. Over the past 15 years, he has authored 29 peer-reviewed original research articles published in high-standard international journals such as Science, Nature and Cell Press, Proceedings of the National Academy of Sciences, EMBO Journal, PLoS Pathogens, Brain and Acta Neuropathologica. He has also authored 2 methodology and 5 review articles. Webster CP, Smith EF, Bauer CS, Moller A, Hautbergue GM, Ferraiuolo L, Myszczynska MA, Higginbottom A, Walsh MJ, Whitworth AJ, Kaspar BK, Meyer K, Shaw PJ, Grierson AJ, De Vos KJ (2016) The C9orf72 protein interacts with Rab1a and the ULK1 complex to regulate initiation of autophagy. EMBO J. 35 (15):1656-76 Hautbergue GM (2016) Widespread RNA Dysregulation in Neurodegeneration: Challenges and Opportunities. Editorial. Austin Neurol. 1(1):1002 Rust A, Hassan HHA, Sedelnikova S, Niranjan D, Hautbergue G, Abbas SA, Partridge L, Rice D, Binz T and Davletov B. Two complementary approaches for intracellular delivery of exogenous enzymes. Sci. Rep. 5:12444 Cooper-Knock J, Bury JJ, Heath PR, Wyles M, Higginbottom A, Gelsthorpe C, Highley JR, Hautbergue G, Rattray M, Kirby J and Shaw PJ (2015) C9ORF72 GGGGCC Expanded Repeats Produce Splicing Dysregulation which Correlates with Disease Severity in Amyotrophic Lateral Sclerosis. PLoS One 10 (5): e0127376