Dr Barbara Clough PhD, FHEA

School of Biosciences
Postdoctoral Research Fellow

Contact details

Telephone: 0121 414 7533
Email: b.clough@bham.ac.uk
Twitter: @babs_clough

Address: Institute of Microbiology and Infection
Biosciences Building
University of Birmingham
Edgbaston
Birmingham, B15 2TT

Barbara is a Research Fellow working in Dr Eva Frickel’s laboratory within the Institute of Microbiology and Infection (IMI), in the College of Life and Environmental Sciences. Barbara works on the cell intrinsic immune response to intracellular pathogens in human cells. She is particularly interested in the interferon gamma (IFNg)-driven control of Toxoplasma gondii at the parasite/cell interface, using high-content fluorescent microscopy to discover the mechanisms of infection control in different cell types.

Qualifications

PhD in Parasitology (Malaria), National Institute for Medical Research, London

PGCHE, University of Birmingham

BSc (Hons) Medical Cell Biology and Biochemistry, University of Liverpool

Biography

Barbara started her research career at the University of Liverpool where she gained a BSc in Medical Cell Biology and Biochemistry. She became interested in infectious disease research during work experience at the Liverpool School of Tropical Medicine. This interest was pursued in Dr Iain Wilson’s laboratory at the National Institute for Medical Research, London where she obtained a PhD in the biophysical regulation of malarial parasite invasion into red blood cells.

Her interest in malaria continued into a post-doctoral fellowship at St Mary’s Hospital Medical School, where she studied the pathogenesis of malaria with Professor Geoffrey Pasvol. Barbara’s research focused on the cytoadherence phenotypes in malarial parasites and their relationship to red blood cell invasion. Barbara joined Dr Eva Frickel’s group at the National Institute for Medical Research in 2012 as a Senior Investigator Scientist and started research into cell-intrinsic immunity to Toxoplasma gondii, focusing on interferon gamma (IFNg)-driven host defence to the parasite. She continued investigating the IFNg- and ubiquitin-dependent restriction of Toxoplasma when the laboratory moved to the Francis Crick Institute in 2016. As a Principal Laboratory Research Scientist, Barbara used fluorescence microscopy, proximity biotinylation and mass spectrometry techniques to uncover novel host defence proteins co-operating in Toxoplasma control.

Barbara is currently a postdoctoral research fellow working with Dr Eva Frickel at the IMI, University of Birmingham. Her research into innate host response to Toxoplasma is focused on infection in human retinal cells as a model for ocular toxoplasmosis.

Teaching

Personal Academic Tutor (Post-Graduate)

Postgraduate supervision

MSci Biochemistry/ Biological Sciences final year project supervision
MSc Molecular Biotechnology/ Microbiology and Infection project supervision

Research

Host-pathogen interaction, Innate immunity, Cell biology, Toxoplasma, Malaria

Publications

Clough, B., Fisch, D., Mize, T.H., et al (2023) p97/VCP targets Toxoplasma gondii vacuoles for parasite restriction in interferon-stimulated human cells. BioRxiv doi: https://doi.org/10.1101/2023.06.20.545566

Rivera-Cuevas, Y., Clough, B. and Frickel, E-M. (2023) Human guanylate-binding proteins in intracellular pathogen detection, destruction, and host cell death induction. Current Opinion in Immunology 84:102373. doi: 10.1016/j.coi.2023.102373

Fisch, D., Clough, B., Khan, R., Healy, L. and Frickel E-M. (2022) Toxoplasma proximal and distal control by GBPs in human macrophages. Pathogens and Disease 79 https://doi.org/10.1093/femspd/ftab058

Fisch, D., Evans, R., Clough, B., et al (2021) HRMAn 2.0: Next-generation artificial intelligence-driven analysis for broad host-pathogen interactions. Cellular Microbiology 23 (7) p. e13349

Fisch, D., Clough, B., Domart, M-C., et al (2020) Human GBP1 differentially targets Salmonella and Toxoplasma to licence recognition of microbial ligands and caspase-mediated death. Cell Reports 32(6):108008. doi:10.1016/j.celrep.2020.108008.

Fisch, D., Clough, B. and Frickel, E-M. (2019) Human immunity to Toxoplasma gondii. PLoS Pathog 15(12): e1008097

Yakimovich, A., Huttunen, M., Samolej, J., Clough, B. et al (2019) Mimicry embedding for advanced neural network training of 3D biomedical micrographs. bioRxiv doi: https://doi.org/10.1101/820076

Fisch, D., Clough, B. et al (2019) Human GBP1 differentially targets Salmonella and Toxoplasma to license recognition of microbial ligands and caspase-mediated death. bioRxiv doi: https://doi.org/10.1101/792804

Clough, B. et al (2019) C57BL/6 and 129 inbred mouse strains differ in Gbp2 and Gbp2b expression in response to inflammatory stimuli in vivo. Wellcome Open Res 4:124 https://doi.org/10.12688/wellcomeopenres.15329.1

Fisch., D., Yakimovich, A., Clough, B. et al (2019) Defining host-pathogen interactions employing an artificial intelligence workflow. eLife 8e40560 doi:10.7554/eLife.40560

Foltz, C., Napolitani, A., Khan, R., Clough. B. et al (2017) TRIM21 is critical for survival of Toxoplasma gondii infection and localises to GBP-positive parasite vacuoles. Sci Reports 7(1):5209

Clough, B. and Frickel, E-M. (2017) The Toxoplasma parasitophorous vacuole: an evolving host-parasite frontier. Trends Parasitol. 33(6):473-488

Clough, B. et al (2016) K63-linked ubiquitination targets Toxoplasma gondii for endo-lysosomal destruction in IFNg-stimulated human cells. PLoS Pathog 12(11):e1006027

Johnston, A.C., Piro, A., Clough, B. et al (2016) Human GBP1 does not localise to pathogen vacuoles but restricts Toxoplasma gondii. Cellular Microbiol 18(8): 1056-1067

Ansell, K.H., Jones, H.M., Whalley, D., Hearn, A., Taylor, D.L., Patin, E.C., Chapman, T.M., Osborne, S.A., Wallace, C., Birchall, K., Large, J., Bouloc, N., Smiljanic-Hurley, E., Clough, B. et al (2014) Biochemical and antiparasitic properties of inhibitors of the Plasmodium falciparum calcium-dependent kinase PfCDPK1. Antimicrob Agents Chemother 58(10):6032-6043

Wright, M.H., Clough, B. et al (2014) Validation of N-myristoyltransferase as an antimalarial drug target using an integrated chemical biology approach. Nature Chem 6(2):112-121

Chapman, T.M., Osborne, S.A., Wallace, C., Birchall, K., Bouloc, N., Jones, H.M., Ansell, K.H., Taylor, D., Clough, B. et al (2014) Optimisation of an imidazopyridazine series of inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PFCDPK1) J Med Chem 57(8):3570-3587

Niedelman, W., Sprokholt, J.K., Clough, B. (2013) Cell death of gamma interferon-stimulated human fibroblasts upon Toxoplasma gondii infection induces early parasite egress and limits parasite replication. Infect Immun 81(12): 4341-4349

Large, J.M., Osborne, S.A., Smiljanic-Hurley, E., Ansell, K.H., Jones, H.M., Taylor, D., Clough, B. et al (2013) Imidazopyridazines as potent inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1): preparation and evaluation of pyrazole linked analogues. Bioorg Medicinal Chem Lett 23(21):6019-6024

Chapman, T.M., Osborne, S.A., Bouloc, N., Large, J.M., Wallace, C., Birchall, K., Ansell, K.H., Jones, H.M., Taylor, D., Clough, B. et al (2013) Substituted imidazopyridazines are potent and selective inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) Bioorg Med Chem Lett 23(10): 3064-3069

Petrovic, A., Davis, C.T., Rangachari, K., Clough, B., et al (2008) Hydrodynamic characterization of the SufBC and SufCD complexes and their interaction with fluorescent adenosine nucleotides. Protein Science 17: 1264-1274

Sato, S., Clough, B., et al (2004) Enzymes for heme biosynthesis are found in both the mitochondrion and plastid of the malaria parasite Plasmodium falciparum. Protist 155:117-125.

Clough, B. and Wilson, R.J.M. (2001) Antibiotics and the plasmodial plastid organelle. In: Antimalarial Chemotherapy. Editor: Philip J Rosenthal. Humana Press Inc., New Jersey, USA

Ellis, K.E.S., Clough, B., et al (2001) Nifs and Sufs in malaria. Mol. Microbiol. 41:973-981.

Clough, B., et al (1999) Antibiotic inhibitors of organellar protein synthesis in Plasmodium falciparum. Protist 150: 189-195.

Blackman, M.J. and Clough, B. (1999) Meeting report: Molecular Parasitology Meeting, Woods Hole, USA September 13-17 Protist 150: 3-6.

Blackman, M.J., Fujioka, H., Stafford, W.H.L., Sajid, M., Clough, B., et al (1998) A subtilisin-like protein in secretory organelles of Plasmodium falciparum. J. Biol Chem. 273:23398-23409

Clough, B., et al (1998) Plasmodium falciparum: The importance of IgM in the rosetting of parasite-infected erythrocytes. Exptl. Parasitol. 89: 129-132

Clough, B., Atilola, F.A. and Pasvol, G. (1998) The role of rosetting in the multiplication of Plasmodium falciparum: rosette formation neither enhances nor targets parasite invasion into uninfected red cells. Brit. J. Haematol. 100: 99-104.

Clough, B. (1998) Cell lines for Biotechnologists. In: Cell and Tissue Culture: Laboratory Procedures in Biotechnology. Editors: Alan Doyle and J. Bryan Griffiths. John Wiley & Sons Ltd., England.

Clough, B., et al (1997) Thiostrepton binds to malarial plastid rRNA. FEBS Lett. 406: 123-125.

Clough, B., et al (1996) Plasmodium falciparum lacks sialidase and trans-sialidase activity. Parasitology 112: 443-449.

Clough, B., et al (1995) Mechanism of regulation of malarial invasion by extraerythrocytic ligands. Molecular and Biochemical Parasitology 69: 19-27.

Pasvol, G., Clough, B., et al (1995) The pathogenesis of severe falciparum malaria. In Baillière’s Clinical Infectious Diseases pp249-270. Editor: Pasvol, G. Baillière Tindall, London.

Bayley, P.M. and Clough, B. (1995) Application of optical microscopy to cellular dynamics: studies of fluorescence photobleaching (FRAP) of erythrocyte membrane proteins using the confocal microscope. J Trace and Microprobe Techniques 13: 217-225.

Field, S.J., Pinder, J.C., Clough, B., et al (1993) Actin in the merozoite of the malaria parasite, Plasmodium falciparum. Cell Motil. Cytoskeleton 25: 43-48.

Pasvol, G. Carlsson, J. and Clough, B. (1993) The red cell membrane and invasion by malarial parasites. In Bailière’s Cinical Haematology 6: 513-534. Editors: Tanner, M.J.A. and Anstee, D.J. Baillière Tindall, London.

Pasvol, G. Clough, B. and Carlsson, J. (1992) Malaria and the red cell membrane. Blood Reviews 6: 183-192.

Schofield, A.E., Tanner, M.J.A., Pinder, J.C., Clough, B., et al (1992) Basis of unique red cell membrane properties in hereditary ovalocytosis. J. Mol Biol. 233: 949-958.

Rangachari, K., Beavan, G.H., Nash, G.B., Clough, B., et al (1989) A study of red cell membrane properties in relation to malarial invasion. Mol. Biochem. Parasitol. 34: 63-74.

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