Professor Guillaume Hautbergue

FRSB, PhD, PGCertHE, FHEA

Neuroscience, School of Medicine and Population Health

Professor of 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)

Sheffield Institute for Translational Neuroscience (SITraN)

Full contact details

Professor Guillaume Hautbergue
Neuroscience, School of Medicine and Population Health
Sheffield Institute for Translational Neuroscience (SITraN)
385a Glossop Road
Sheffield
S10 2HQ

Profile

Professor of Translational RNA Biology: January 2023 - present

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

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

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

Allen SP, Al Sultan A, Kabucho Kibirige E, Tonkiss E, Hamer KJ, Castelli LM, Lin Y-H, Roscoe S, Stefanidis N, Mead RJ , Highley JR et al (2023) A Y374X TDP43 truncation leads to an altered metabolic profile in amyotrophic lateral sclerosis fibroblasts driven by pyruvate and TCA cycle intermediate alterations. Frontiers in Aging Neuroscience, 15.
Moll T, Odon V, Harvey C, Collins MO, Peden A, Franklin J, Graves E, Marshall JN, Dos Santos Souza C, Zhang S , Castelli L et al (2023) Low expression of EXOSC2 protects against clinical COVID-19 and impedes SARS-CoV-2 replication.. Life Sci Alliance, 6(1).
Bauer CS, Webster CP, Shaw AC, Kok JR, Castelli LM, Lin Y-H, Smith EF, Illanes-Álvarez F, Higginbottom A, Shaw PJ , Azzouz M et al (2022) Loss of TMEM106B exacerbates C9ALS/FTD DPR pathology by disrupting autophagosome maturation. Frontiers in Cellular Neuroscience, 16.
Marchi PM, Marrone L, Brasseur L, Coens A, Webster CP, Bousset L, Destro M, Smith EF, Walther CG, Alfred V , Marroccella R et al (2022) C9ORF72-derived poly-GA DPRs undergo endocytic uptake in iAstrocytes and spread to motor neurons.. Life Sci Alliance, 5(9).
Castelli LM, Benson BC, Huang W-P, Lin Y-H & Hautbergue GM (2022) RNA helicases in microsatellite repeat expansion disorders and neurodegeneration. Frontiers in Genetics, 13. View this article in WRRO
Karyka E, Berrueta Ramirez N, Webster CP, Marchi PM, Graves EJ, Godena VK, Marrone L, Bhargava A, Ray S, Ning K , Crane H et al (2022) SMN-deficient cells exhibit increased ribosomal DNA damage. Life Science Alliance, 5(8), e202101145-e202101145.
Benson BC, Shaw PJ, Azzouz M, Highley JR & Hautbergue GM (2021) Proteinopathies as Hallmarks of Impaired Gene Expression, Proteostasis and Mitochondrial Function in Amyotrophic Lateral Sclerosis. Frontiers in Neuroscience, 15.
Hautbergue GM, Cleary JD, Guo S & Ranum LPW (2021) Therapeutic strategies for C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia. Current Opinion in Neurology.
Castelli LM, Cutillo L, Souza CDS, Sanchez-Martinez A, Granata I, Lin Y-H, Myszczynska MA, Heath PR, Livesey MR, Ning K , Azzouz M et al (2021) SRSF1-dependent inhibition of C9ORF72-repeat RNA nuclear export : genome-wide mechanisms for neuroprotection in amyotrophic lateral sclerosis. Molecular Neurodegeneration, 16(1).
Castelli LM, Huang W-P, Lin Y-H, Chang K-Y & Hautbergue GM (2021) Mechanisms of repeat-associated non-AUG translation in neurological microsatellite expansion disorders. Biochemical Society Transactions.
Gatto N, Dos Santos Souza C, Shaw AC, Bell SM, Myszczynska MA, Powers S, Meyer K, Castelli LM, Karyka E, Mortiboys H , Azzouz M et al (2020) Directly converted astrocytes retain the ageing features of the donor fibroblasts and elucidate the astrocytic contribution to human CNS health and disease. Aging Cell.
De Marco M, Manca R, Kirby J, Hautbergue G, Blackburn DJ, Wharton S & Venneri A (2020) The association between polygenic hazard scores and clinical markers of Alzheimer’s disease following stratification for APOE genotype. Alzheimer's & Dementia, 16(S4).
De Marco M, Manca R, Kirby J, Hautbergue GM, Blackburn DJ, Wharton SB & Venneri A (2020) The Association between Polygenic Hazard and Markers of Alzheimer’s Disease Following Stratification for APOE Genotype. Current Alzheimer Research, 17.
Myszczynska MA, Ojamies PN, Lacoste AMB, Neil D, Saffari A, Mead R, Hautbergue GM, Holbrook JD & Ferraiuolo L (2020) Applications of machine learning to diagnosis and treatment of neurodegenerative diseases. Nature Reviews Neurology, 16, 440-456. View this article in WRRO
Allen S, Hall B, Castelli L, Frances L, Woof R, Siskos A, Kouloura E, Gray E, Thompson A, Talbot K , Higginbottom A et al (2019) Astrocyte adenosine deaminase loss increases motor neuron toxicity in amyotrophic lateral sclerosis. Brain, 142(3), 586-605. View this article in WRRO
López KLR, Simpson JE, Watson LC, Mortiboys H, Hautbergue GM, Bandmann O & Highley JR (2019) TIGAR inclusion pathology is specific for Lewy body diseases. Brain Research, 1706, 218-223. View this article in WRRO
Cooper-Knock J, Moll T, Ramesh T, Castelli L, Beer A, Robins H, Fox I, Niedermoser I, Van Damme P, Moisse M , Robberecht W et al (2019) Mutations in the Glycosyltransferase Domain of GLT8D1 Are Associated with Familial Amyotrophic Lateral Sclerosis. Cell Reports, 26(9), 2298-2306.e5. View this article in WRRO
Ferraiuolo L, Varcianna AE, Myszczynska MA, Castelli LM, O'Neill B, Kim Y, Talbot J, Nyberg S, Nymali I, Heath PR , Stopford MJ et al (2019) Micro-RNAs secreted through astrocyte-derived extracellular vesicles cause neuronal network degeneration in C9orf72 ALS.. EBioMedicine, 40, 626-635. View this article in WRRO
Shaw MP, Higginbottom A, Mcgown A, Castelli LM, James E, Hautbergue GM, Shaw PJ & Ramesh TM (2018) Stable transgenic C9orf72 zebrafish model key aspects of the ALS/FTD phenotype and reveal novel pathological features. Acta Neuropathologica Communications, 6(1). View this article in WRRO
Iannitti T, Scarrott J, Likhite S, Coldicott IRP, Lewis KE, Heath PR, Higginbottom A, Myszczynska MA, Milo M, Hautbergue GM , Meyer K et al (2018) Translating SOD1 Gene Silencing toward the Clinic: A Highly Efficacious, Off-Target-free, and Biomarker-Supported Strategy for fALS. Molecular Therapy : Nucleic Acids, 12, 75-88. View this article in WRRO
Morgan SV, Garwood CJ, Jennings L, Simpson JE, Castelli LM, Heath PR, Mihaylov SR, Vaquéz-Villaseñor I, Minshull TC, Ince PG , Dickman MJ et al (2018) Proteomic and cellular localisation studies suggest non-tight junction cytoplasmic and nuclear roles for occludin in astrocytes. European Journal of Neuroscience, 47(12), 1444-1456. View this article in WRRO
Rust A, Shah S, Hautbergue G & Davletov B (2018) Burkholderia Lethal Factor 1, a Novel Anti-Cancer Toxin, Demonstrates Selective Cytotoxicity in MYCN-Amplified Neuroblastoma Cells. Toxins, 10(7), 261-261. View this article in WRRO
Castelli LM, Lin YH, Ferraiuolo L, Sanchez-Martinez A, Ning KE, Azzouz M, Whitworth A, Shaw PJ & Hautbergue GM (2018) SRSF1-dependent nuclear export of C9ORF72 repeat transcripts: targeting toxic gain-of-functions induced by protein sequestration as a selective therapeutic strategy for neuroprotection. Therapeutic Targets for Neurological Diseases, 4. View this article in WRRO
Cooper-Knock J, Robins H, Niedermoser I, Wyles M, Heath PR, Higginbottom A, Walsh T, Kazoka M, Ince PG, Hautbergue GM , McDermott CJ et al (2017) Targeted Genetic Screen in Amyotrophic Lateral Sclerosis Reveals Novel Genetic Variants with Synergistic Effect on Clinical Phenotype. Frontiers in Molecular Neuroscience, 10, 370-370. View this article in WRRO
Chandran JS, Sharp PS, Karyka E, Aves-Cruzeiro JMDC, Coldicott I, Castelli L, Hautbergue G, Collins MO & Azzouz M (2017) Site Specific Modification of Adeno-Associated Virus Enables Both Fluorescent Imaging of Viral Particles and Characterization of the Capsid Interactome. Scientific Reports, 7(1). View this article in WRRO
Hautbergue GM (2017) RNA Nuclear Export: From Neurological Disorders to Cancer. Adv Exp Med Biol, 1007, 89-109. View this article in WRRO
Walker C, Herranz-Martin S, Karyka E, Liao C, Lewis K, Lukashchuk V, Chiang S-C, Ray S, Mulcahy PJ, Jurga M , Tsagakis I et al (2017) C9orf72 Expansion Disrupts ATM-mediated Chromosomal Break Repair. Nature Neuroscience, 20, 1225-1235. View this article in WRRO
Hautbergue GM, Castelli LM, Ferraiuolo L, Sanchez-Martinez A, Cooper-Knock J, Higginbottom A, Lin YH, Bauer CS, Dodd JE, myszczynska MA , Alam SM et al (2017) SRSF1-dependent nuclear export inhibition of C9ORF72 repeat transcripts prevents neurodegeneration and associated motor deficits. Nature Communications, 8. View this article in WRRO
Stopford M, Higginbottom A, Hautbergue , Cooper-Knock , Mulcahy , De Vos K, Renton A, Pliner H, Calvo A, Chio A , Traynor B et al (2017) C9ORF72 hexanucleotide repeat exerts toxicity in a stable, inducible motor neuronal cell model, which is rescued by partial depletion of Pten. Human Molecular Genetics, 26(6), 1133-1145. View this article in WRRO
Webster CP, Smith EF, Bauer CS, Moller A, Hautbergue GM, Ferraiuolo L, Myszczynska MA, Higginbottom A, Walsh MJ, Whitworth AJ , Kaspar BK et al (2016) The C9orf72 protein interacts with Rab1a and the ULK1 complex to regulate initiation of autophagy. EMBO Journal, 35(15), 1656-1676. View this article in WRRO
Hautbergue GM (2016) Widespread RNA dysregulation in neurodegeneration: Challenges and Opportunities. Austin Neurology, 1(1). View this article in WRRO
Rust A, Hassan HHA, Sedelnikova S, Niranjan D, Hautbergue G, Abbas SA, Partridge L, Rice D, Binz T & Davletov B (2015) Two complementary approaches for intracellular delivery of exogenous enzymes. Scientific Reports, 5, 12444-12444. View this article in WRRO
Cooper-Knock J, Higginbottom A, Stopford MJ, Highley JR, Ince PG, Wharton SB, Pickering-Brown S, Kirby J, Hautbergue GM & Shaw PJ (2015) Antisense RNA foci in the motor neurons of C9ORF72-ALS patients are associated with TDP-43 proteinopathy. Acta Neuropathologica, 130(1), 63-75. View this article in WRRO
Cooper-Knock J, Bury JJ, Heath PR, Wyles M, Higginbottom A, Gelsthorpe C, Highley JR, Hautbergue G, Rattray M, Kirby J & Shaw PJ (2015) C9ORF72 GGGGCC Expanded Repeats Produce Splicing Dysregulation which Correlates with Disease Severity in Amyotrophic Lateral Sclerosis. PLOS ONE, 10(5), e0127376-e0127376. View this article in WRRO
Tazzyman S, Hautbergue G, Khurram A, Bryan M, Chantry A & Fragiadaki M (2015) The application of antibotoxsome, a novel cytotoxic conjugate, in cell death in in vitro models of pancreatic, liver, breast, cervical cancer, and myeloma.. Journal of Clinical Oncology, 33(15_suppl), e12018-e12018.
Snijders AP, Hautbergue GM, Bloom A, Williamson JC, Minshull TC, Phillips HL, Mihaylov SR, Gjerde DT, Hornby DP, Wilson SA , Hurd PJ et al (2015) Arginine methylation and citrullination of splicing factor proline- and glutamine-rich (SFPQ/PSF) regulates its association with mRNA. RNA, 21(3), 347-359. View this article in WRRO
Walsh MJ, Cooper-Knock J, Dodd JE, Stopford MJ, Mihaylov SR, Kirby J, Shaw PJ & Hautbergue GM (2015) Invited Review: Decoding the pathophysiological mechanisms that underlie RNA dysregulation in neurodegenerative disorders: a review of the current state of the art. Neuropathology and Applied Neurobiology, 41(2), 109-134. View this article in WRRO
Caballero-Lima D, Hautbergue GM, Wilson SA & Sudbery PE (2014) In C andida albicans hyphae, Sec2p is physically associated with SEC2 mRNA on secretory vesicles. Molecular Microbiology, 94(4), 828-842. View this article in WRRO
Cooper-Knock J, Walsh MJ, Higginbottom A, Robin Highley J, Dickman MJ, Edbauer D, Ince PG, Wharton SB, Wilson SA, Kirby J , Hautbergue GM et al (2014) Sequestration of multiple RNA recognition motif-containing proteins by C9orf72 repeat expansions.. Brain, 137(Pt 7), 2040-2051. View this article in WRRO
Tunnicliffe RB, Hautbergue GM, Wilson SA, Kalra P & Golovanov AP (2014) Competitive and Cooperative Interactions Mediate RNA Transfer from Herpesvirus Saimiri ORF57 to the Mammalian Export Adaptor ALYREF. PLoS Pathogens, 10(2). View this article in WRRO
Walsh MJ, Dodd JE & Hautbergue GM (2013) Ribosome-inactivating proteins. RNA Biology, 10(12), 1760.
Walsh MJ, Dodd JE & Hautbergue GM (2013) Ribosome-inactivating proteins: potent poisons and molecular tools.. Virulence, 4(8), 774-784.
Chang C-T, Hautbergue GM, Walsh MJ, Viphakone N, van Dijk TB, Philipsen S & Wilson SA (2013) Chtop is a component of the dynamic TREX mRNA export complex.. EMBO J, 32(3), 473-486.
Viphakone N, Hautbergue GM, Walsh M, Chang CT, Holland A, Folco EG, Reed R & Wilson SA (2013) Erratum: TREX exposes the RNA-binding domain of Nxf1 to enable mRNA export.. Nat Commun, 4, 2377.
Viphakone N, Hautbergue GM, Walsh M, Chang C-T, Holland A, Folco EG, Reed R & Wilson SA (2012) TREX exposes the RNA-binding domain of Nxf1 to enable mRNA export.. Nat Commun, 3, 1006. View this article in WRRO
Hautbergue GM & Wilson SA (2012) BLF1, the first Burkholderia pseudomallei toxin, connects inhibition of host protein synthesis with melioidosis.. Biochem Soc Trans, 40(4), 842-845.
Knuckles P, Vogt MA, Lugert S, Milo M, Chong MMW, Hautbergue GM, Wilson SA, Littman DR & Taylor V (2012) Drosha regulates neurogenesis by controlling neurogenin 2 expression independent of microRNAs.. Nat Neurosci, 15(7), 962-969.
Phelan MM, Goult BT, Clayton JC, Hautbergue GM, Wilson SA & Lian L-Y (2012) The structure and selectivity of the SR protein SRSF2 RRM domain with RNA.. Nucleic Acids Res, 40(7), 3232-3244. View this article in WRRO
Hautbergue G (2012) [Characterisation of Burkholderia pseudomallei Lethal Factor 1 (BLF1). A breakthrough against melioidosis].. Med Sci (Paris), 28(3), 262-264.
Cruz-Migoni A, Hautbergue GM, Artymiuk PJ, Baker PJ, Bokori-Brown M, Chang C-T, Dickman MJ, Essex-Lopresti A, Harding SV, Mahadi NM , Marshall LE et al (2011) A Burkholderia pseudomallei toxin inhibits helicase activity of translation factor eIF4A.. Science, 334(6057), 821-824. View this article in WRRO
Jackson BR, Boyne JR, Noerenberg M, Taylor A, Hautbergue GM, Walsh MJ, Wheat R, Blackbourn DJ, Wilson SA & Whitehouse A (2011) An interaction between KSHV ORF57 and UIF provides mRNA-adaptor redundancy in herpesvirus intronless mRNA export.. PLoS Pathog, 7(7), e1002138. View this article in WRRO
Van Hateren NJ, Das RM, Hautbergue GM, Borycki A-G, Placzek M & Wilson SA (2011) FatJ acts via the Hippo mediator Yap1 to restrict the size of neural progenitor cell pools.. Development, 138(10), 1893-1902.
Tunnicliffe RB, Hautbergue GM, Kalra P, Jackson BR, Whitehouse A, Wilson SA & Golovanov AP (2011) Structural basis for the recognition of cellular mRNA export factor REF by herpes viral proteins HSV-1 ICP27 and HVS ORF57.. PLoS Pathog, 7(1), e1001244. View this article in WRRO
Clayton JC, Phelan M, Goult BT, Hautbergue GM, Wilson SA & Lian L-Y (2011) The 1H, 13C and 15N backbone and side-chain assignment of the RRM domain of SC35, a regulator of pre-mRNA splicing.. Biomol NMR Assign, 5(1), 7-10.
Hung ML, Hautbergue GM, Snijders AP, Dickman MJ & Wilson SA (2010) Arginine methylation of REF/ALY promotes efficient handover of mRNA to TAP/NXF1.. Nucleic Acids Res, 38(10), 3351-3361. View this article in WRRO
Walsh MJ, Hautbergue GM & Wilson SA (2010) Structure and function of mRNA export adaptors.. Biochem Soc Trans, 38(Pt 1), 232-236.
Clayton JC, Phelan M, Goult BT, Hautbergue GM, Wilson SA & Lian L-Y (2010) The 1H, 13C and 15N backbone and side-chain assignment of the RRM domain of SC35, a regulator of pre-mRNA splicing. Biomolecular NMR Assignments, 1-4.
Hautbergue GM, Hung M-L, Walsh MJ, Snijders APL, Chang C-T, Jones R, Ponting CP, Dickman MJ & Wilson SA (2009) UIF, a New mRNA export adaptor that works together with REF/ALY, requires FACT for recruitment to mRNA.. Curr Biol, 19(22), 1918-1924.
Hautbergue GM & Golovanov AP (2008) Increasing the sensitivity of cryoprobe protein NMR experiments by using the sole low-conductivity arginine glutamate salt.. J Magn Reson, 191(2), 335-339.
Hautbergue GM, Hung M-L, Golovanov AP, Lian L-Y & Wilson SA (2008) Mutually exclusive interactions drive handover of mRNA from export adaptors to TAP.. Proc Natl Acad Sci U S A, 105(13), 5154-5159.
Tintaru AM, Hautbergue GM, Hounslow AM, Hung M-L, Lian L-Y, Craven CJ & Wilson SA (2007) Structural and functional analysis of RNA and TAP binding to SF2/ASF.. EMBO Rep, 8(8), 756-762.
Tintaru AM, Hautbergue GM, Hounslow AM, Lian L-Y, Wilson SA & Craven CJ (2007) Assignment of 1H, 13C, and 15N resonances for SF2 RNA recognition motif 2.. J Biomol NMR, 38(2), 193.
Hargous Y, Hautbergue GM, Tintaru AM, Skrisovska L, Golovanov AP, Stevenin J, Lian L-Y, Wilson SA & Allain FH-T (2006) Molecular basis of RNA recognition and TAP binding by the SR proteins SRp20 and 9G8.. EMBO J, 25(21), 5126-5137.
Golovanov AP, Hautbergue GM, Tintaru AM, Lian L-Y & Wilson SA (2006) The solution structure of REF2-I reveals interdomain interactions and regions involved in binding mRNA export factors and RNA.. RNA, 12(11), 1933-1948.
Golovanov AP, Hautbergue GM, Wilson SA & Lian L-Y (2006) Assignment of 1H, 13C, and 15N resonances for the REF2-I mRNA export factor.. J Biomol NMR, 36 Suppl 1, 41.
Williams BJL, Boyne JR, Goodwin DJ, Roaden L, Hautbergue GM, Wilson SA & Whitehouse A (2005) The prototype gamma-2 herpesvirus nucleocytoplasmic shuttling protein, ORF 57, transports viral RNA through the cellular mRNA export pathway.. Biochem J, 387(Pt 2), 295-308.
Golovanov AP, Hautbergue GM, Wilson SA & Lian L-Y (2004) A simple method for improving protein solubility and long-term stability.. J Am Chem Soc, 126(29), 8933-8939.
Bouchoux C, Hautbergue G, Grenetier S, Carles C, Riva M & Goguel V (2004) CTD kinase I is involved in RNA polymerase I transcription.. Nucleic Acids Res, 32(19), 5851-5860.
Hautbergue G & Goguel V (2001) Activation of the cyclin-dependent kinase CTDK-I requires the heterodimerization of two unstable subunits.. J Biol Chem, 276(11), 8005-8013.
Hautbergue G & Goguel V (1999) The yeast C-type cyclin Ctk2p is phosphorylated and rapidly degraded by the ubiquitin-proteasome pathway.. Mol Cell Biol, 19(4), 2527-2534.
Mihaylov SR, Castelli LM, Lin Y-H, Gül A, Soni N, Hastings C, Flynn HR, Păun O, Dickman MJ, Snijders AP , Goldstone R et al () The master energy homeostasis regulator PGC-1α exhibits an mRNA nuclear export function. Nature Communications, 14(1).
Hautbergue G () A cell-penetrant peptide blocking C9ORF72-repeat RNA nuclear export reduces the neurotoxic effects of dipeptide repeat proteins. Science Translational Medicine.
Cooper‐Knock J, Julian TH, Feneberg E, Highley JR, Sidra M, Turner MR, Talbot K, Ansorge O, Allen SP, Moll T , Shelkovnikova T et al () Atypical TDP ‐43 protein expression in an ALS pedigree carrying a p. Y374X truncation mutation in TARDBP. Brain Pathology.
Rust A, Partridge L, Davletov B & Hautbergue G () The Use of Plant-Derived Ribosome Inactivating Proteins in Immunotoxin Development: Past, Present and Future Generations. Toxins, 9(11), 344-344. View this article in WRRO
Patera F, Hautbergue GM, Wilson P, Evans PC, Ong ACM & Fragiadaki M () Ankhd1 enhances polycystic kidney disease development via promoting proliferation and fibrosis.

Conference proceedings papers

Cooper-Knock J, Moll T, Ramesh T, Castelli L, Shaw C, Al-Chalabi A, McDermott C, Hautbergue G & Shaw P (2019) 11.30 Mutations in the glycosyltransferase domain of GLT8D1 cause ALS. Journal of Neurology Neurosurgery & Psychiatry, Vol. 90(12) (pp e10)
Cooper-Knock J, Moll T, Ramesh T, Castelli L, Shaw C, Al-Chalabi A, McDermott C, Hautbergue G & Shaw P (2019) MUTATIONS IN THE GLYCOSYLTRANSFERASE DOMAIN OF GLT8D1 CAUSE ALS. JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, Vol. 90(12) (pp E20-E21)
Alves-Cruzeiro JM, Karyka E, Bauer C, Coldicott I, Simon S, Hautbergue GM, Webster C, Myszczynska M, Higginbottom A, Ferraiuolo L & Azzouz M (2019) Gene editing as a potential therapeutic approach for ALS/FTD-associated with expanded C9ORF72. HUMAN GENE THERAPY, Vol. 30(8) (pp A22-A22)
Alves-Cruzeiro J, Karyka E, Bauer C, Coldicott I, Hautbergue G, Webster C, Castelli L, Simon S, Myszczynska M, Ferraiuolo L & Azzouz M (2019) AAV-mediated gene editing as a potential therapeutic approach for C9ORF72-linked ALS/FTD. HUMAN GENE THERAPY, Vol. 30(11) (pp A96-A96)
Allen SP, Hall B, Castelli L, Francis L, Woof R, Higginbottom A, Myszczynska M, Allen CF, Stopford MJ, Webster CP , De Vos K et al (2018) Inosine reverses motor neuron toxicity observed in amyotrophic lateral sclerosis patient astrocytes with an adenosine deaminase deficiency. Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1859 (pp e23-e23)
Tazzyman S, Hautbergue G, Khurram A, Bryan M, Chantry A & Fragiadaki M (2015) The application of antibotoxsome, a novel cytotoxic conjugate, in cell death in in vitro models of pancreatic, liver, breast, cervical cancer, and myeloma.. Journal of Clinical Oncology, Vol. 33(15)

Datasets

Gatto N, Souza CDS, Bell S, Shaw A, Myszczynska M, Powers S, Meyer K, Heath P, Castelli L, Karyka E , Mortiboys H et al Directly converted astrocytes retain the ageing features of the donor fibroblasts and elucidate the astrocytic contribution to human CNS health and disease..

Preprints

Marchi PM, Marrone L, Brasseur L, Bousset L, Webster CP, Destro M, Smith EF, Walther CG, Alfred V, Marroccella R , Robinson D et al () C9orf72-derived poly-GA DPRs undergo endocytic uptake in iNPC-derived astrocytes and spread to motor neurons, Cold Spring Harbor Laboratory.
Mihaylov SR, Castelli LM, Lin Y-H, Gül A, Soni N, Hastings C, Flynn HR, Dickman MJ, Snijders AP, Bandmann O , Mortiboys H et al () The master energy homeostasis regulator PGC-1α couples transcriptional co-activation and mRNA nuclear export, Cold Spring Harbor Laboratory.
Castelli LM, Sanchez-Martinez A, Lin Y-H, Upadhyay SK, Higginbottom A, Cooper-Knock J, Gül A, Walton A, Montmasson C, Cohen R , Bauer CS et al () A cell-penetrant peptide blocking C9ORF72-repeat RNA nuclear export suppresses neurodegeneration, Cold Spring Harbor Laboratory.
Castelli LM, Cutillo L, Souza CDS, Sanchez-Martinez A, Granata I, Myszczynska MA, Heath PR, Livesey MR, Ning K, Azzouz M , Shaw PJ et al () Safety and efficacy of C9ORF72-repeat RNA nuclear export inhibition in amyotrophic lateral sclerosis, Cold Spring Harbor Laboratory.
Cooper-Knock J, Moll T, Ramesh T, Castelli L, Beer A, Robins H, Fox I, Niedermoser I, Van Damme P, Robberecht W , Hardiman O et al () Mutations in the Glycosyltransferase Domain of GLT8D1 Cause Amyotrophic Lateral Sclerosis.

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 and memberships

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).

School of Medicine and Population Health