Staff Profile
Dr Paula Salgado
Senior Lecturer in Macromolecular Crystallography, Theme Lead
- Email: paula.salgado@ncl.ac.uk
- Telephone: 01912087432
- Personal Website: https://salgadolab.org
- Address: Molecular Mechanisms of Life Theme
Biosciences Institute
Faculty of Medical Sciences
2nd Floor Cookson Building
Newcastle University
Newcastle upon Tyne, NE2 4HH, UK
Research Positions
2019 - present Theme Lead for Molecular Mechanisms of Life Theme, FMS, Newcastle University
2019 - present Senior Lecturer of Macromolecular Crystallography, NUBI, Newcastle University
2012 - 2019 Lecturer of Macromolecular Crystallography, ICaMB, Newcastle University
2011 - 2012 Research Associate, Division of Cell and Molecular Biology, Department of Life Sciences, Imperial College London, UK
2008 – 2011 Research Associate, Division of Molecular Biosciences, Department of Life Sciences, Imperial College London, UK
2005 – 2008 Research Associate, School of Crystallography, Birkbeck College/University College, London, UK
Education
2001 – 2005 PhD in Structural Biology, Henry Wellcome Trust Building for Human Genetics, University of Oxford and Open University. "Structural Studies of RNA-dependent RNA polymerases" Supervisors: Dr Jon Grimes and Prof Dave I Stuart
1993 -1999 BSc in Biochemistry, Science Faculty & Institute of Biomedical Sciences “Abel Salazar”, University of Porto, Portugal. Research Project: "Structure determination of transthyretin variants"
Research Awards
March 2022 - March 2025 - Research Grant MRC
October 2017 - October 2021 - Wellcome Trust Collaborative Award
November 2014 - November 2017 - New Investigator Research Grant, MRC
April 2013 - March 2014 - Royal Society Research Grant
March - June 2011 - Wellcome Trust Value In People Award
Oct 01 - Oct 2005 - PhD Fellowship (part of Human Frontier Science Program Research Grant)
As a structural biologist interested in proteins associated with pathogenicity and disease, I have recently established a C. difficile Structural Microbiology group focusing on detailed structural and functional characterisation of proteins involved in key pathogenicity pathways in this major human pathogen. Combining these approaches, we are interested in C. difficile spores, the dormant, resistant cell forms that are the transmission vehicle, as well as surface proteins and their role in infection.
Clostridioides difficile S-layer
C. difficile is now the most prevalent hospital acquired infection in the UK. These gram-positive bacteria have an outside para-crystalline layer (S-layer) that is presumed to act as a protective shield and that is thought to be implicated in virulence, host interaction and immune activation. We focus on understanding S-layer organisation, primarily by determining the structure of the major S-layer protein constituent, SlpA. This work is part of a Wellcome Trust Collaborative Award with colleagues from Sheffield and Glasgow universities.
We are also studying other cell wall proteins identified in C. difficile, aiming to understand their macromolecular details with our structural studies that complement work developed by our collaborators.
Sporulation engulfment machinery
Work in the Salgado lab, awarded an MRC New Investigator Grant (Nov 2014), has identified two essential proteins involved in the early stages of sporulation (Crawshaw et al., 2014, Serrano et al., 2016). We have also contributed to elucidating details of the engulfment mechanism to start defining the complex machinery involved in this process, which we termed the engulfasome (Kelly and Salgado, 2019). We have recently been awarded a Research Grant from the MRC to continue our work to unravel the molecular mechanism of engulfment in C. difficile.
Supervisor:
PhD students
- Victoria Burge
- Charlotte Roughton
- Gilly Wang
MRes/MSci, UG projects and summer vacancies
Module leader:
Studying Life at the Molecular Level (MMB8018), MRes module
Lecturer:
Advanced Protein Analysis (BGM2062), BSc Biochemistry
- Crawshaw AD, Basle A, Salgado PS. A practical overview of molecular replacement: Clostridioides difficile PilA1, a difficult case study. Acta Crystallographica Section D: Structural Biology 2020, 76, 261-271.
- Julius C, Salgado PS, Yuzenkova Y. Metabolic cofactors NADH and FAD act as non-canonical initiating substrates for a primase and affect replication primer processing in vitro. Nucleic Acid Research 2020, 48(13), 7298-7306.
- Kelly A, Salgado PS. The engulfasome in C. difficile: Variations on protein machineries. Anaerobe 2019, 60, 102091.
- Dembek M, Kelly A, Barwinska-Sendra A, Vollmer D, Biboy J, Gray J, Vollmer W, Salgado PS. Peptidoglycan degradation machinery in Clostridium difficile forespore engulfment. Molecular Microbiology 2018, 110(3), 390-410.
- Dembek M, Willing SE, Hong HA, Hosseini S, Salgado PS, Cutting SM. Inducible expression of spo0A as a universal tool for studying sporulation in Clostridium difficile. Frontiers in Microbiology 2017, 8, 1793.
- Serrano M, Crawshaw AD, Dembek M, Monteiro JM, Pereria FC, Gomes de Pinho M, Fairweather NF, Salgado PS, Henriques AO. The SpollQ-SpolllAH complex of Clostridium difficile controls forespore engulfment and late stages of gene expression and spore morphogenesis. Molecular Microbiology 2016, 100(1), 204-228.
- Warren AJ, Crawshaw AD, Trincao J, Aller P, Alcock S, Nistea I, Salgado PS, Evans G. In vacuo X-ray data collection from graphene-wrapped protein crystals. Acta Crystallographica Section D: Biological Crystallography 2015, 71, 2079-2088.
- Crawshaw AD, Serrano M, Stanley WA, Henriques AO, Salgado PS. A mother cell-to-forespore channel: current understanding and future challenges. FEMS Microbiology Letters 2014, 358(2), 129-136.
- Lin J, Soon-Hwan O, Jones R, Garnett JA, Salgado PS, Rusnakova S, Matthews S, Hoyer LL, Cota E. The Peptide-Binding Cavity is Essential for Als3-mediated Adhesion of Candida albicans to Human Cells. Journal of Biological Chemistry 2014, M114, 547877.
- Douse CH, Green JL, Salgado PS, Simpson PJ, Thomas JC, Langsley G, Holder AA, Tate EW, Cota E. Regulation of the Plasmodium motor complex: Phosphorylation of myosin A tail-interacting protein (MTIP) loosens its grip on MyoA. Journal of Biological Chemistry 2012, 287(44), 36968-36977.
- Taylor JD, Zhou Y, Salgado PS, Patwardhan A, McGuffie M, Pape T, Grabe G, Ashman E, Constable SC, Simpson PJ, Lee W, Cota E, Chapman MR, Matthews SJ. Atomic resolution Insights into Curli Fiber Biogenesis. Structure 2011, 19(9), 1307-1316.
- Salgado PS, Yan R, Rowan F, Cota E. Expression, crystallization, preliminary X-ray data analysis of NT-ALS9, a fungal adhesin from Candida albicans. Acta Crystallographica. Section F: Structural Biology and Crystallization Communications 2011, 67(4), 467-470.
- Salgado PS, Taylor JD, Cota E, Mathews SJ. Extending the usability of the phasing power of diselenide bonds: SeCys SAD phasing of CsgC using a non-auxotrophic strain. Acta Crystallographica. Section D: Biological Crystallography 2011, 67(p.1), 8-13.
- Salgado PS, Yan R, Taylor JD, Buchnell L, Jones R, Hoyer L, Matthews SJ, Simpson P, Cota E. Structural basis for the broad specificity to host-cell ligands by the pathogenic fungus Candida albicans. Proceedings of the National Academy of Sciences 2011, 108(38), 15775-15779.
- Poranen MM, Salgado PS, Koivunen MRL, Wright S, Bamford DH, Stuart DI, Grimes JM. Structural explanation for the role of Mn2+ in the activity of Φ6 RNA-dependent RNA polymerase. Nucleic Acids Research 2008, 36(20), 6633-6644.
- Salgado PS, Laurila MRL, Makeyev EV, Bamford DH, Stuart DI, Grimes JM. The structure of an RNAi polymerase links RNA silencing and transcription. PLoS Biology 2006, 4(12), e434.
- Laurila MRL, Salgado PS, Stuart DI, Grimes JM, Bamford DH. Back-priming mode of Phi6 RNA-dependent RNA polymerase. Journal of General Virology 2005, 86(2).
- Laurila MR, Salgado PS, Makeyev EV, Nettelship J, Stuart DI, Grimes JM, Bamford DH. Gene silencing pathway RNA-dependent RNA polymerase of Neurospora crassa: yeast expression, crystallization of selenomethionated QDE-1 protein. Journal of Structural Biology 2005, 149(1), 111-115.
- Salgado PS, Walsh MA, Laurila MRL, Stuart DI, Grimes JM. Going soft and SAD with manganese. Acta Biol Crystallographica D 2005, D61(1), 108-111.
- Salgado PS, Makeyev EV, Butcher SJ, Bamford DH, Stuart DI, Grimes JM. The structural basis for RNA specificity, Ca2+ inhibition of an RNA-dependent RNA polymerase. Structure 2004, 12(2), 307-316.