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Mary Phillips-Jones

Dr. Mary Phillips-Jones

Senior Lecturer in Biochemistry & Microbiology

School of Pharmacy and Biomedical Sciences

Maudland Building, MB133

MPhillips-Jones@uclan.ac.uk

Subject Areas: Allied Health, Biosciences, Pharmacy and Pharmacology and Dentistry

Mary has a B.Sc. (Hons) (1979) and a Ph.D (1983) in Microbiology from UCW, Aberystwyth. She joined the School after 16 years as Lecturer/Senior Lecturer in the Faculty of Biological Sciences, University of Leeds (1995-2012) and postdoctoral research at the Universities of Nottingham (1986-1989), Sheffield (1984-1985; 1989-1995) and Amsterdam (1995). Her research includes the molecular mechanisms of bacterial signalling and response to environmental change, and regulation of gene expression.

Mary is the Director of the Membranes, Membrane Proteins & Peptides. 

Full Profile

Qualifications:

Ph.D. Microbial Physiology, University College of Wales, Aberystwyth, 1983.

B.Sc. (Hons) Microbiology, University College of Wales, Aberystwyth, 1979.

Listen to Mary’s research being carried out at UCLan and about the growing problems of antimicrobial resistance that we all face on BBC Radio Lancashire – her appearance on the John Gillmore Show, 10th June 2016.

Mary undertook her PhD studies under the supervision of Dr Muriel E. Rhodes-Roberts and Prof Douglas B. Kell on inhibitors of bacterial electron transport at the University College of Wales in Aberystwyth before moving to the laboratory of Prof John R. Guest FRS at the University of Sheffield to study the succinate dehydrogenase complex genes of Bacillus subtilis. She initiated her own research programme at the University of Nottingham on clostridial molecular genetics, and continued with that programme at the University of Sheffield where she developed a lux-based reporter gene system that works in the anaerobe C. perfringens. At Sheffield she also investigated regulators of photosynthesis gene expression with Prof C. Neil Hunter, discovering the Reg (Prr) two-component system of Rhodobacter sphaeroides. Following a related project funded by the Royal Society (London) to investigate the photoactive yellow protein of R. sphaeroides in the laboratory of Prof Klaas Hellingwerf in the University of Amsterdam, she took up a lectureship at the University of Leeds. There she developed her interests in bacterial two-component signal transduction systems; for example, with Prof Peter J.F. Henderson she successfully heterologously overexpressed and purified the first intact membrane sensor kinase protein (published in Journal of Molecular Biology) and solved the three-dimensional structure of the DNA-binding domain of the 'essential' VicR response regulator of pathogenic Enterococcus faecalis (with Prof Simon E.V. Phillips). In a long-standing collaboration with Prof Mike P. Williamson (University of Sheffield) the NMR solution structure of the C-terminal domain of RegA (PrrA) was solved, providing insights into how such a promiscous regulator might bind to so many target genes and the work was published in Nucleic Acids Research. Most recently Mary has been involved in expressing and purifying the genome complement of intact sensor kinases of the hospital-acquired infection agent Enterococcus faecalis. The vast majority were shown to be purifyable and active, and currently activating ligands and inhibitory drugs are being identified that target these membrane proteins.

Mary joined UCLan in 2012 (and is a Visiting Senior Lecturer at the University of Leeds and the Astbury Centre for Structural Molecular Biology), where she continues her research programme. Biophysical techniques are currently being applied to studies of E. faecalis membrane sensor kinases and their ligand/inhibitor interactions. For example, in collaboration with Drs Giuliano Siligardi and Rohanah Hussain at Beamline 23 of the Diamond Light Source Ltd, she has developed circular dichroism-based methods for quantitative analysis of ligand (and drug) binding by membrane proteins (published in Biochimica et Biophysica Acta Biomembranes) - the first time to the authors knowledge that CD has been used to obtain quantitative binding data for any membrane protein.

Publications

Rohanah Hussain, Stephen E. Harding, Charlotte S. Hughes, Pikyee Ma, Simon G. Patching, Shalini Edara, Giuliano Siligardi, Peter J.F. Henderson, Mary K. Phillips-Jones (2016) Purification of bacterial membrane sensor kinases and biophysical methods for determination of their ligand and inhibitor interactionsBiochemical Society Transactions 44: 810-823

Siligardi, G., Hussain, R., Patching, S.G. & Phillips-Jones, M.K. (2014). Ligand- and drug-binding studies of membrane proteins revealed through circular dichroism spectroscopy. Biochim. Biophys. Acta Biomembr. 1838: 34-42.

Patching, S.G., Edara, S., Ma, P. Nakayama, J., Hussain, R., Siligardi, G. & Phillips-Jones, M.K. (2012) Interactions of the intact FsrC membrane histidine kinase with its pheromone ligand GBAP revealed through synchrotron radiation circular dichroism. Biochim. Biophys. Acta Biomembr. 1818, 1595-1602.

Ma, P., Yuille, H.M., Blessie, V., Göhring, N., Iglói, Z, Nishiguchi, K., Nakayama, J., Henderson, P.J.F. & Phillips-Jones, M.K. (2008) Expression, purification and activities of the entire family of intact membrane sensor kinases from Enterococcus faecalis. Mol. Membr. Biol. 25, 449-47

Thesis - Claire Pogson, Kelsall MSc - July 2013 full length (.pdf 7.81mb)

More publications

Research

Research Activities

Mary has over 30 years research experience in bacterial physiology, and molecular and structural biology. Her research interests lie principally with how bacteria sense and respond to environmental change, focusing particularly on the structure and function of bacterial signal transduction pathways (mainly two-component signal transduction systems) and regulators of bacterial gene expression. Research includes investigations of intact sensory proteins that are usually located in the bacterial membrane and are responsible for sensing environmental stimuli and stresses, and also their partner cytosolic regulators that effect appropriate adaptive responses (usually by binding to specific promoters and thereby changing gene expression). She has received >£1 million of BBSRC, MRC-MoD and other grant funding in the past 10 years for studies of the sensing mechanisms of the membrane sensory histidine kinase components in pathogenic bacteria.

Most recently, and following a move to UCLan in 2012 she co-developed and established circular dichroism-based methods for quantitating ligand and antimicrobial peptide interactions with membrane proteins (in collaboration with the Diamond Light Source Ltd). The principal systems/regulators (and their associated pathways) under investigation are those found in a range of pathogenic bacteria associated with hospital-acquired infections. The main approaches and tools of the research are: biophysical methods to investigate ligand-protein interactions of the signal transduction proteins involved, including the intact membrane sensor kinases; elucidation of the three-dimensional structures with a view to structure-based drug design; and phosphorylation-based activity assays to screen and identify candidate signalling ligands, inhibitors and drugs.

Research Projects

Quorum sensing mechanisms in clinical enterococci

Ligand- and inhibitor-sensor kinase interactions in Gram positive pathogens

Structural and molecular characterisation of bacterial signal transduction pathways

External Activities

Editorial Board Member for Nature Scientific Reports (2016 - ).

Co-Organiser of a Meeting hosted by the Biochemical Society on the 70th Anniversary of the discovery of hydrogen bonds in DNA, to be held in 2017.

External Examiner (MSc programmes) at the University of Nottingham.

Guest Editor for Biochemica et Biophysica Acta Biomembranes (2012-2013)

Pool Member of BBSRC Research Grant Committees (2009-2014)

Circular dichroism lectures on M.Sc. Applied Biotechnology courses, University of Nottingham (2014 - )

Teaching Activities and Responsibilities

Module tutor for BL2216 (Cellular Investigations), BL3224 (Healthcare Decisions & Dilemmas) and PJ3202 (Microbiological and Immunological Bases of Disease).

Mary is involved in the teaching of microbiology, biochemistry and molecular biology on the MSc and BSc programmes for biomedical sciences and pharmacy within the School. She utilises her research knowledge and experience in several modules and offers undergraduate and postgraduate research projects that align with ongoing research projects in her laboratory. Projects students have been involved with joint research work conducted at the Diamond Synchotron. Mary also participates in the UCLan Undergraduate Research Internship Scheme in which students are provided with an opportunity during the summer vacation to sample what research work is like

Memberships

Pool Member of BBSRC Research Grant Committees (2009-2014)
Guest Editor for Biochemica et Biophysica Acta Biomembranes (2012-2013)
Member of the British Biophysical Society (2013 - present)
Member of the Biochemical Society (1998 - present)
Member of the Society for General Microbiology (1982 - present )
Fellow of the Higher Education Academy (2013 - present)
Member of Society for Laboratory Automation & Screening

Conferences

Most recent invitation:

Invited speaker at the 8th International Conference on Gram-positive Microorganisms (18th International Conference on Bacilli), Montecatini Terme, Italy, June 2015.

Invited speaker at Society for Laboratory Automation & Screening and Scottish Universities Meeting on Cutting Edge Technologies for Drug Screening, University of Edinburgh, May 2015.