Dr Guillaume Hautbergue

FRSB, PhD, PGCertHE, FHEA

Department of Neuroscience

Senior Lecturer in Translational RNA Biology

Head of the RNA Biology Laboratory

g.hautbergue@sheffield.ac.uk
+44 114 222 2252
+44 114 222 2278 (Administrator: Heather Cartledge)

Full contact details

Dr Guillaume Hautbergue
Department of Neuroscience
385a Glossop Road
Sheffield
S10 2HQ
Profile

Senior Lecturer in Translational RNA Biology January 2019 - present

Lecturer in Translational Biology December 2012 - December 2018
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, particularly focusing on ALS/MND, for the development of novel therapeutic strategies of neuroprotection.

Senior Experimental Officer March 2010 – November 2012

  1. 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. Department of Molecular Biology and Biotechnology, University of Sheffield, U.K. March 2010 – July 2012
  2. 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).
Qualifications

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

Research interests

Our research focuses on identifying pathophysiological consequences of widespread RNA dysregulation in neurodegeneration in order to design, develop and test novel therapeutic strategies of neuroprotection using viral and non-viral gene therapy approaches.

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?

Publications

Journal articles

Conference proceedings papers

Research group

Post-Doctoral Research Associates

  • Dr Lydia Castelli
  • Dr Ya-Hui Lin

PhD Students

  • Ms Charlotte Mason (PI)
  • Ms Bridget Benson (PI)
  • Mr Aytaç Gul (PI)
  • Ms Monika Myszczynska (Secondary supervisor; PI: Dr Laura Ferraiuolo)
  • Ms Emily Graves (Secondary supervisor; PI: Prof Mimoun Azzouz)
  • Ms Amy Keerie (Secondary supervisor; PI: Dr Richard Mead)
  • Mr Paolo Marchi (Secondary supervisor; PI: Prof Mimoun Azzouz)

Former PhD students for which I was the PI:

  • Dr Jennifer Dodd (now at University of Liverpool)
  • Dr Simeon R. Mihaylov (now at the Francis Crick Institute)

Undergraduate Research Technicians

  • Ms Nikita Soni (2018-19)

Former students

  • Mr Robin Pritchard (2016-17)
  • Ms Amy Walton (2017-18).

Student awards:

Mr Theo Wing (MSc Translational Neuroscience student) was awarded the "Neuroscience Departmental Prize" for best lab project and presentation as well as "The Jody De Vos MND Research Award 2017" for best project in Motor Neurone Disease research.

Ms Michelle Vermeulen (MSc Translational Neuroscience student) shared the "Neuroscience Departmental Prize" for best lab project and presentation in 2018.

Grants
  • Medical Research Council (MRC)
  • Biotechnology and Biological Sciences Research Council (BBSRC)
  • Motor Neurone Disease Association
  • Fondation Thierry Latran
  • The Royal Society
Teaching activities
  • MBChB Research SSC Academic Lead for the Medical School (March 2018 – present)

  • Innovation in Medical Education: development of a novel student-led approach, SACK (Student Assessment of Current Knowledge), to promote the active learning of undergraduates. Research projects are also available from a teacher perspective during the Student Selected Component of Phase 3A medical students. Please, contact Dr Guillaume Hautbergue if interested.

  • MSc in Translational Neuroscience, MSc in Genomic Medicine, MSc in Molecular Medicine:
    - Module MED620: Introduction to RNA biology – gene expression in health
    - Module MED623: RNA dysregulation in Amyotrophic Lateral Sclerosis
    - Module MED670: Introduction to Human Genetics & Genomics
    - Laboratory research projects

  • 1-year research placement undergraduate students from Sheffield Hallam University
  • Laboratory projects concerning the molecular mechanisms of neurodegeneration in MND/ALS are available during the Student Selected Component of Phase 2A medical students.

  • Outreach engagement with the local Westbourne Junior School and Tapton Secondary School. Nuffield Research Placement laboratory projects are offered to selected Year-11 Tapton School students with support from the Nuffield Foundation and the Biology teacher Dr Nick Harris. Congratulations to our former members, Ms Nithya Rathi, Ms Sreenidhi Athi, Ms Nemah Mabger and Ms Khadija Kaabar, who were all awarded a Gold CREST Award (CREativity in Science and Technology Award) from the British Science Association.

  • Outreach activities with primary and secondary schools and the public during Science week and Festival of the Mind. Congratulations to our former members, Ms Nithya Rathi, Ms Sreenidhi Athi, Ms Nemah Mabger, Ms Khadija Kaabar, Ms Emma Bray, Ms Lucy Hanley and Mr Aria Izadi who were all awarded a Gold CREST Award (CREativity in Science and Technology Award) from the British Science Association. Emma Bray and Aria Izadi were also finalists of the National Big Bang UK Young Scientists and Engineers Fair.

  • Outreach activities with primary and secondary schools, the public, patients and carers during Science week, Festival of the Mind and SITraN open days/symposium.
Professional activities
  • Editorial board member of the journal “RNA and Disease” (since 2014).
  • Member of the Departmental Strategic Vision and Appointment Committee (Since 2018)

  • Member of the Department of Neuroscience Learning and Teaching Committee (since 2018)

  • Department of Neuroscience Personal Academic Tutor Coordinator (since 2016)

  • Member of the Department of Neuroscience Health and Safety Committee (since 2015)

  • Academic representative of the Department of Neuroscience Reward and Recognition group (since 2015)

  • Academic representative of the Departmental of Neuroscience Outreach Committee that organizes public and school events (since 2014)

  • Responsible and Holder of the Departmental licenses for radioactive work (since 2013)

  • Invited Lecturer at the University of Oxford Autumn School in Neuroscience

  • PhD examination: (i) External examiner on 1 occasion; (ii) Internal examiner on 4 occasions

  • Outreach activities in local schools and for public events in Sheffield

  • Member of the Biochemical Society

Reviewing activities


Scientific articles:

Nucleic Acids Research, Nature, Nature Methods, Nature Chemical Biology, Scientific Reports, Acta Neuropathologica Communications, Human Molecular Genetics, PLOS journals, Toxins, The International Journal of Biochemistry and Cell Biology, Journal of Proteome Research, Medicinal Research Review, Biomolecules, etc.

Research grant applications

United Kingdom: Medical Research Council (MRC), Biotechnology and Biological Sciences Research Council (BBSRC), MRC Foundation (MRF), Action Medical Research, Great Ormond Street Hospital, Leverhulme Trust, Association of British Neurologists for Clinical Research Training Fellowships

International

French AFM Telethon; Dutch ZonMw Vidi programs, Belgian Foundation against Cancer

Awards

  • Selected member of the University of Sheffield Crucible (2012 - 2013), a competitive UK programme for improving communication, outreach activities and interdisciplinary collaborations
  • Best seminar prize at the national RNA UK 2012 conference
  • Research Associate Wellcome Trust VIP Award (2005/2006)
  • French Ph.D. Fellowships: - "Fondation pour la Recherche Médicale" (October 2001 – December 2001) - "Association pour la Recherche sur le Cancer" (October 2000 – September 2001) - "Ministère de la Recherche et de l’Education Nationale" (October 1997 – September 2000)
  • French National Defence bronze medal (1997)
  • First National Prize in Biochemistry in the competitive examination "Concours Général" – France and French Overseas Countries (1990)
Research group collaborators
  • ALS and neurodegeneration: Prof Dame Pamela Shaw, Prof Mimoun Azzouz, Dr Laura Ferraiuolo, Dr Johnathan Cooper-Knock, Dr Tennore Ramesh, Dr Richard Mead and Dr Kurt De Vos (SITraN, University of Sheffield, UK); Dr Alexander Withworth (MRC Mitochondrial Biology Unit, University of Cambridge); Prof Kung-Yao Chang (National Chung-Hsing University, Taiwan); Prof David Lyons (Centre for Discovery Brain Sciences, University of Edinburgh, UK); Dr Yun-Ru (Ruby) Chen (Academia Sinica, Taiwan); Dr Adrian Isaacs (University College London Institute of Neurology, UK); Prof Sherif El-Khamisy (Molecular Biology and Biotechnology, University of Sheffield, UK).
  • Structure determination of ribonucleoprotein complexes: Prof Frédéric HT Allain (Institute of Molecular Biology and Biophysics, ETH Zürich, Switzerland) and Dr Cyril Dominguez (Department of Molecular and Cell Biology, University of Leicester, UK)
  • Protein methylation and citrullination, mass spectrometry, quantitative proteomics: Dr Mark Dickman (Chemical and Biological Engineering, University of Sheffield, UK).
  • Integration, computational and statistical analysis of large data: Dr Marta Milo (Biomedical Science, University of Sheffield, UK), Dr Luisa Cutillo (School of Mathematics, University of Leeds, UK); Dr Mario R Guarracino (High Performance Computing and Networking Institute, Italy)
  • Use of Ribosome-Inactivating Proteins (RIPs) as molecular tools and potential therapeutic vehicles/compounds for specific intra-neuronal delivery: Prof Bazbek Davletov (Biomedical Science, University of Sheffield, UK), Dr Lynda Partridge (Molecular Biology and Biotechnology, University of Sheffield, UK) and Prof Jim Deuchars (University of Leeds, UK).
  • Parkinson’s disease: Prof Oliver Bandmann and Dr Heather Mortiboys (SITraN, University of Sheffield).
  • Ageing of the brain and neuropathology: Prof Steve Wharton and Dr Robin Highley (SITraN, University of Sheffield).