缅北禁地

Background

Frank is Dean of the Biosciences Institute (NUBI) and holds a Personal Chair in Microbial Biotechnology.

Frank joined 缅北禁地 in August 2018, first as a Professor in the Faculty of Science, Agriculture & Engineering (SAgE) and from 2022 as a Professor in the Faculty of Medical Sciences. He studied biochemistry at the University of Edinburgh (1988-1992) where he became interested in bacterial bioenergetics, membrane biology and metal-containing enzymes. He then studied for a PhD in the then Department of Biochemistry at the University of Dundee (1992-1996) before moving to Norwich, England, as a Postdoctoral Research Assistant investigating protein targeting in bacteria. In 2000 Frank was lucky enough to be awarded a Royal Society University Research Fellowship to lead his own research group in the School of Biological Sciences, University of East Anglia, Norwich. During this time Frank and his team predominantly studied the biochemistry of bacterial Tat proofreading chaperones, small proteins that recognise and bind tightly to twin-arginine signal peptides. The quality of this work was recognised by the award of early career research prizes. In 2007 Frank returned to the University of Dundee to take up a Personal Chair in Bacterial Physiology in the then College of Life Sciences. There his research interests turned again towards bacterial bioenergetics and new projects on nickel-dependent hydrogenases and molybdenum-containing enzymes were initiated. Frank was elected a Fellow of the Royal Society of Edinburgh in 2011.

Education

1996 PhD Bacterial Biochemistry, University of Dundee

1992 BSc (Hons) Biological Sciences (Biochemistry), University of Edinburgh

Research Posts

2018-present: Professor of Microbial Biotechnology, 缅北禁地

2007-2018: Professor of Bacterial Physiology, University of Dundee

2000-2007: Royal Society University Research Fellow, University of East Anglia

1998-2000: Postdoctoral Research Assistant, University of East Anglia, Norwich

1996-1998: Postdoctoral Research Assistant, John Innes Centre, Norwich

University Posts

2024-present: Dean, 缅北禁地 Biosciences Institute, Faculty of Medical Sciences

2022-2024: Deputy Dean, 缅北禁地 Biosciences Institute, Faculty of Medical Sciences

2019-2022: Associate Dean (Research & Innovation), Faculty of Science, Agriculture & Engineering

2018-present: Professor of Microbial Biotechnology, 缅北禁地

2014-2018: Member, Senatus Academicus, University of Dundee

2012-2015: Associate Dean for Research-Led Teaching, University of Dundee

2007-2018: Professor of Bacterial Physiology, University of Dundee

Current External Academic Posts and Community Service

2024-2026: Deputy Chair, BBSRC Committee E (Fellowships)

2021-2024: International Partner, REDEFINE:H₂E International Future Lab in H₂ Energy, TU Munich

2021-2024: External Examiner (PGT), MSc Biotechnology, MSc Infection & Immunity University of Liverpool

2018-2025: Honorary Treasurer & Trustee, The Biochemical Society

Previous Academic Posts and Community Service

2022: Member, The Andrew Carnegie Trust Research Incentive Grants Panel

2021-2023: Member, Royal Society of Edinburgh Fellowship Review Committee

2019-2023: Member, BBSRC Committee E (David Phillips & Discovery Fellowships)

2019-2023: External Examiner (UGT), BSc Biology, BSc Biochemistry, University of Kent

2018-2023: External Examiner (PGT), MSc Molecular Biotechnology, University of Birmingham

2021-2022: Deputy Chair, BBSRC 21ALERT Panel

2020-2022: Full Panel Member, Research England REF2021 Sub-Panel-A-5: Biological Sciences

2020-2022: Deputy Chair, BBSRC Strategic LoLa Committee (SLC)

2020-2021: Deputy Chair, BBSRC 20ALERT Panel

2019-2020: Member, BBSRC 19ALERT Panel

2019: Member, The Andrew Carnegie Trust Research Incentive Grants Panel

2018-2022: Member, Faculty of 1000 (Microbiology: Microbial Physiology and Metabolism)

2018: Chair, BBSRC One Health Approaches to Vaccine Development Panel

2018-2020: Chair, IBioIC CTP Board

2018: Member, FRIMEDBIO Expert Committee, Research Council of Norway

2017-2018: External Examiner (PGT), MSc Industrial Biotechnology, University of York

2017: Member, BBSRC 17ALERT Panel

2016-2018: IBioIC Scientific Advisory Board

2016-2017: Chair, BBSRC Committee B (Plants, Microbes, Food and Sustainability)

2014-2018: External Examiner (PGT), MSc Synthetic Biology & Biotechnology, University of Edinburgh

2013-2017: External Examiner (UGT), BSc & MSci Biochemistry, University of York

2013-2016: Deputy Chair, BBSRC Committee B (Plants, Microbes, Food and Sustainability)

2013: Member, joint BBSRC-DBT Sustainable Biofuels and Bioenergy Panel

2012-2017: Senior Editor, Microbiology

2012-2017: Editor, Biochemical Journal

Measures of Esteem

2014: Chancellor's Award for Outstanding Contribution, University of Dundee

2011: Fellow of the Royal Society of Edinburgh

2011: Fellow of the Royal Society of Biology

2010: The Wain Medal, University of Kent

2009: FEBS Young Scientist Prize

2007: The Colworth Medal, The Biochemical Society

2006: The Fleming Prize, The Microbiology Society

Hydrogenases, formate dehydrogenases and hydrogen-dependent carbon dioxide reductases.

Currently Funded by: BBSRC (BB/Y004302/1) and EPSRC ReNU CDT Program

Previously Funded by: BBSRC (BB/S000666/1), CO2Chem (EPSRC), CCnet NIBB and the IBioIC-BBSRC CTP (BB/T508743/1) 

In biology, molecular hydrogen (H₂) is produced or consumed by hydrogenases, which catalyse the reversible interconversion of H₂ to protons and electrons. They are ancient, widespread, and highly diverse and are common in prokaryotic, and some eukaryotic, microbial systems. Formate hydrogenlyase (FHL) has a hydrogenase component that belongs to the ‘Group 4’ of nickel-dependent [NiFe]-hydrogenases and is mainly found in prokaryotes that can grow by anaerobic fermentation. In Escherichia coli, and related g-Proteobacteria such as Pectobacterium atrospeticum, FHL catalyses the disproportionation of formic acid (HOOCH) to H₂ and carbon dioxide (CO₂). The FHL-1 version of formate hydrogenlyase from E. coli has been characterised by us and other research groups in the field. E. coli FHL-1 is encoded by hycBCDEFG and the separate fdhF gene and is predicted to share an evolutionary ancestor with the mitochondrial Complex I. It comprises a soluble peripheral arm containing a molybdenum- and selenium-dependent formate dehydrogenase (FdhF) linked via two [Fe-S]-cluster-containing subunits (HycBF) to a core [NiFe]-hydrogenase (HycEG) - termed ‘Hyd-3’. The peripheral arm is attached to the cytoplasmic face of the bacterial inner membrane by a ‘membrane arm’ containing two integral membrane subunits (HycCD). The ability of FHL-1 to generate H₂ gas while the microorganism ferments sugars could potentially have impact in renewable bioenergy or biofuel initiatives.

FHL-1 is reversible and under conditions where H₂ and CO₂ are relatively high it can perform Hydrogen-Dependent Carbon Dioxide Reductase (HDCR) activity (Roger et al. 2018 - doi: 10.1016/j.cub.2017.11.050 and Roger et al. 2021 - doi: ). This is not the physiological role of the enzyme, but this activity has exciting biotechnological applications if it can be harnessed and optimised. In addition, for those of you interested in astrobiology or evolutionary biology, the HDCR version of FHL-1 may well have been one of the first biological mechanisms to evolve that was capable of 'fixing' CO₂ in to organic matter.

The FHL-2 complex contains a Group 4 nickel-dependent hydrogenase component termed ‘Hyd-4’. FHL-2 also differs from FHL-1 by the presence of three additional transmembrane subunits (HyfBEF). A fully functional FHL-2 complex was identified by us in the phytopathogen P. atrosepticum and its contribution to formate-dependent H₂ production in intact cells was unambiguously demonstrated in an open access paper published in Molecular Microbiology (Finney et al., 2019 - doi: 10.1111/mmi.14370). The P. atrospeticum hyfABCDEFGHIJK operon encodes the FHL-2 Hyd-4 module, the complete membrane arm, and associated accessory proteins. The P. atrosepticum FHL-2 gene cluster also contains a putative formate-responsive transcriptional regulator (hyfR) and genes encoding a metal-dependent formate dehydrogenase FdhF (sharing 85 % overall sequence identity with FdhF from E. coli but lacking selenocysteine), and an alternative formate dehydrogenase small subunit, HydN (related to HyfA). 

Current research in the Sargent team is focused on understanding the basic physiology and biochemistry of FHL-1 and FHL-2, and on engineering these enzymes for biotechnological applications.

Bacterial Protein Secretion Pathways

Currently Funded by: 缅北禁地 Overseas Research Scholarship

Previously Funded by: BBSRC (BB/R016453/1)

Bacteria secrete proteins, enzymes and proteinaceous toxins to their outside environment to allow them to compete for space and resources with other microbes. Clearly, the ribosomes must remain firmly inside the bacterial cell cytoplasm synthesising proteins de novo, thus specialised pathways are required to export proteins across the inner membrane and/or to secrete proteins across the outer membrane. At least nine different protein secretion pathways have been discovered in gram-negative bacteria, and there are a couple more different ones found only in gram-positive bacteria. The Type X (10) Secretion System was identified by us in Serratia marcescens (Hamilton et al. 2014 - doi: 10.1083/jcb.201404127) and is probably present in many other bacteria (Palmer et al. 2021 - doi: 10.1111/mmi.14599). In S. marcescens the TXSS is a two-step pathway that secretes chitinase enzymes to the extracellular milieu, and it relies on the activity of a holin (ChiW) and peptidoglycan hydrolase (ChiX) to catalyse final protein secretion across the outer membrane. Our research suggests the sole role of the holin is to transport ChiX to the periplasm and it is the activity of ChiX that then somehow catalyses the secretion of the chitinases. To add to the mystery, some of the secreted chitinases have no periplasmic targeting peptides, while some do. What do you make of that?

Current research in the Sargent team is investigating the basic biochemistry of the TXSS in S. marcescens using reverse genetics and classical molecular microbiology approaches.

BSc/MRes Degree Programs

CMB1006 Stage 1 Practical Skills in Biomedical and Biomolecular Sciences

NES2304 Stage 2 Microbial Biochemistry            

CMB3000 Stage 3 Research Project             

MMB9098 Stage 4 MRes Research Project             

• Articles

  • Wu Y, Bell A, Thomas GH, Bolam DN, Sargent F, Juge N, Palmer T, Severi E. . Microbiology 2024, 170(8), 001476.
  • Wu Y, Bell A, Thomas GH, Bolam DN, Sargent F, Juge N, Palmer T, Severi E. . Microbiology 2024, 170(3), 001448.
  • Peters K, Sargent F. . Biochimica et Biophysica Acta - Bioenergetics 2023, 1864(1), 148919.
  • Metcalfe GD, Sargent F, Hippler M. . Microbiology 2022, 168, 001167.
  • Roger M, Reed TCP, Sargent F. . Applied and Environmental Microbiology 2021, 87(21), e0029921.
  • Finney AJ, Buchanan G, Palmer T, Coulthurst SJ, Sargent F. . Microbiology 2020, 166(9), 854-860.
  • Finney AJ, Lowden R, Fleszar M, Albareda M, Coulthurst SJ, Sargent F. . Molecular Microbiology 2019, epub ahead of print.
  • Finney AJ, Sargent F. . Advances in Microbial Physiology 2019, 74, 465-486.
  • Costa MAA, Owen RA, Tammsalu T, Buchanan G, Palmer T, Sargent F. . Microbiology 2019, 165(11), 1233-1244.
  • Beaton SE, Evans RM, Finney AJ, Lamont CM, Armstrong FA, Sargent F, Carr SB. . Biochemical Journal 2018, 475(7), 1353-1370.
  • Owen RA, Fyfe PK, Lodge A, Biboy J, Vollmer W, Hunter WN, Sargent F. . Biochemical Journal 2018, 475(2), 415-428.
  • Roger M, Brown F, Gabrielli W, Sargent F. . Current Biology 2018, 28(1), 140-145.
  • Lindenstrauss U, Skorupa P, McDowall JS, Sargent F, Pinske C. . Biochemical Journal 2017, 474(17), 2937-2950.
  • Lamont CM, Kelly CL, Pinske C, Buchanan G, Palmer T, Sargent F. . Microbiology 2017, 163(5), 649-653.
  • Evans RM, Brooke EJ, Wehlin SA, Nomerotskaia E, Sargent F, Carr SB, Phillips SE, Armstrong FA. . Nature Chemical Biology 2016, 12, 46-50.
  • Pinske C, Sargent F. . Microbiology Open 2016, 5(5), 721-737.
  • Kelly CL, Pinske C, Murphy BJ, Parkin A, Armstrong F, Palmer T, Sargent F. . Biotechnology Reports 2015, 8, 94-104.
  • McDowall JS, Hjersing MC, Palmer T, Sargent F. . FEBS Letters 2015, 589(20), 3141-3147.
  • Murphy BJ, Sargent F, Armstrong FA. . Energy and Environmental Science 2014, 7(4), 1426-1433.
  • Bowman L, Flanagan L, Fyfe PK, Parkin A, Hunter WN, Sargent F. . Biochemical Journal 2014, 458(3), 449-458.
  • Wulff P, Day CC, Sargent F, Armstrong FA. . Proceedings of the National Academy of Sciences (USA) 2014, 111(18), 6606-6611.
  • Dow JM, Grahl S, Ward R, Evans R, Byron O, Norman DG, Palmer T, Sargent F. . FEBS Journal 2014, 281(1), 246-260.
  • McDowall JS, Murphy BJ, Haumann M, Palmer T, Armstrong FA, Sargent F. . Proceedings of the National Academy of Sciences of the United States of America 2014, 111, e3948-e3956.
  • Hamilton JJ, Marlow VL, Buchanan G, Guo M, Owen R, de Assis Alcoforado Costa M, Trost M, Coulthurst SJ, Palmer T, Stanley-Wall NR, Sargent F. . Journal of Cell Biology 2014, 207(5), 615-626.

• Review

  • Palmer T, Finney A, Saha CK, Atkinson GC, Sargent F. . Molecular Microbiology 2021, 115(3), 345-355.