Professor Gary Jones

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Biography

Gary joined Leeds Beckett in February 2016. He has held academic and postdoctoral research positions at Maynooth University, National Institutes of Health, University College London and Swansea University. He obtained a BSc... (Hons) Genetics and PhD from University of Liverpool.

Since embarking on a PhD in 1991 Gary’s research focus has been on the use of lower eukaryotic organisms, such as yeast and other fungi, to study aspects of cellular stress. His research expertise is in molecular biology, microbiology and genetics. During his PhD and postdoctoral training he utilized Aspergillus nidulans and Saccharomyces cerevisiae [baker’s yeast] to study DNA repair mechanisms and cellular responses to stresses such as heat shock. Due to the conservation of such molecular responses between diverse species, the findings from studies on simple model organisms such as baker’s yeast are also applicable to more complex cellular systems such as mammals.

Following postdoctoral training Gary established his own research group in 2004 at Maynooth University. He maintained a productive research team producing consistent high-level research outputs and attracting significant competitive research funding from national and international sources. He has an excellent track record of successfully graduating PhD students and high-quality research supervision. During his career Gary’s research has been published in high-impact international bioscience journals such as Cell, PNAS, PLOS Genetics, PLOS Computational Biology, PLOS Pathogens, Nucleic Acids Research and Genome Research amongst others.

Currently Gary’s research is focused on two broad areas i) deciphering the role of the ubiquitous stress response protein Hsp70 in diverse cellular functions, and ii) developing new therapeutic strategies to combat hard to treat fungal diseases, such as invasive aspergillosis. His research involves multidisciplinary approaches involving molecular biology, genetics, microbiology, biochemistry, biophysics, computational biology, genomics, proteomics and mass spectrometry. To utilize such diverse technologies he has established an extensive collaboration network with leading researchers based in Ireland, France, Spain, China and the USA.

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Industry Expertise (2)

Research

Education/Learning

Areas of Expertise (5)

Microbiology

Cellular Stress

Biomedical Sciences

Genetics

Molecular Biology

Education (2)

University of Liverpool: Ph.D., Molecular Biology 1995

University of Liverpool: B.S., Genetics 1991

Links (4)

• University Profile
• Research identifies a new process for how cells can quickly respond and survive when exposed to cellular stresses – School of Health Blog
• Google Scholar Citations
• ResearchGate Citations

Languages (1)

• English

Articles (11)

Gliotoxin-mediated bacterial growth inhibition is caused by specific metal ion depletion

Scientific Reports

2023 Overcoming antimicrobial resistance represents a formidable challenge and investigating bacterial growth inhibition by fungal metabolites may yield new strategies. Although the fungal non-ribosomal peptide gliotoxin (GT) is known to exhibit antibacterial activity, the mechanism(s) of action are unknown, although reduced gliotoxin (dithiol gliotoxin; DTG) is a zinc chelator. Furthermore, it has been demonstrated that GT synergises with vancomycin to inhibit growth of Staphylococcus aureus.

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Gliotoxin and related metabolites as zinc chelators: implications and exploitation to overcome antimicrobial resistance

Essays in Biochemistry

2023 Antimicrobial resistance (AMR) is a major global problem and threat to humanity. The search for new antibiotics is directed towards targeting of novel microbial systems and enzymes, as well as augmenting the activity of pre-existing antimicrobials. Sulphur-containing metabolites (e.g., auranofin and bacterial dithiolopyrrolones [e.g., holomycin]) and Zn2+-chelating ionophores (PBT2) have emerged as important antimicrobial classes.

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A Single Aspergillus fumigatus Gene Enables Ergothioneine Biosynthesis and Secretion by Saccharomyces cerevisiae

International Journal of Molecular Sciences

2022 The naturally occurring sulphur-containing histidine derivative, ergothioneine (EGT), exhibits potent antioxidant properties and has been proposed to confer human health benefits. Although it is only produced by select fungi and prokaryotes, likely to protect against environmental stress, the GRAS organism Saccharomyces cerevisiae does not produce EGT naturally. Herein, it is demonstrated that the recombinant expression of a single gene, Aspergillus fumigatus egtA, in S. cerevisiae results in EgtA protein presence which unexpectedly confers complete EGT biosynthetic capacity.

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At the metal-metabolite interface in Aspergillus fumigatus: towards untangling the intersecting roles of zinc and gliotoxin

Microbiology (Reading)

2021 Cryptic links between apparently unrelated metabolic systems represent potential new drug targets in fungi. Evidence of such a link between zinc and gliotoxin (GT) biosynthesis in Aspergillus fumigatus is emerging. Expression of some genes of the GT biosynthetic gene cluster gli is influenced by the zinc-dependent transcription activator ZafA, zinc may relieve GT-mediated fungal growth inhibition and, surprisingly, GT biosynthesis is influenced by zinc availability.

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Mutational analysis of the Hsp70 substrate-binding domain: Correlating molecular-level changes with in vivo function

Molecular Microbiology

2021 Hsp70 is an evolutionarily conserved chaperone involved in maintaining protein homeostasis during normal growth and upon exposure to stresses. Mutations in the β6/β7 region of the substrate-binding domain (SBD) disrupt the SBD hydrophobic core resulting in impairment of the heat-shock response and prion propagation in yeast.

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Rapid deacetylation of yeast Hsp70 mediates the cellular response to heat stress

Scientific Reports

2019 Hsp70 is a highly conserved molecular chaperone critical for the folding of new and denatured proteins. While traditional models state that cells respond to stress by upregulating inducible HSPs, this response is relatively slow and is limited by transcriptional and translational machinery. Recent studies have identified a number of post-translational modifications (PTMs) on Hsp70 that act to fine-tune its function.

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Involvement of Sulfur in the Biosynthesis of Essential Metabolites in Pathogenic Fungi of Animals, Particularly Aspergillus spp.: Molecular and Therapeutic Implications

Frontiers in Microbiology

2019 Fungal sulfur uptake is required for incorporation into the sidechains of the amino acids cysteine and methionine, and is also essential for the biosynthesis of the antioxidant glutathione (GSH), S-adenosylmethionine (SAM), the key source of methyl groups in cellular transmethylation reactions, and S-adenosylhomocysteine (SAH). Biosynthesis of redox-active gliotoxin in the opportunistic fungal pathogen Aspergillus fumigatus has been elucidated over the past 10 years.

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The C-terminal GGAP motif of Hsp70 mediates substrate recognition and stress response in yeast

Journal of Biological Chemistry

2018 The allosteric coupling of the highly conserved nucleotide- and substrate-binding domains of Hsp70 has been studied intensively. In contrast, the role of the disordered, highly variable C-terminal region of Hsp70 remains unclear. In many eukaryotic Hsp70s, the extreme C-terminal EEVD motif binds to the tetratricopeptide-repeat domains of Hsp70 co-chaperones.

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Rapid deacetylation of yeast Hsp70 mediates the cellular response to heat stress

Scientific Reports volume

2019 Hsp70 is a highly conserved molecular chaperone critical for the folding of new and denatured proteins. While traditional models state that cells respond to stress by upregulating inducible HSPs, this response is relatively slow and is limited by transcriptional and translational machinery. Recent studies have identified a number of post-translational modifications (PTMs) on Hsp70 that act to fine-tune its function.

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The β6/β7 region of the Hsp70 substrate-binding domain mediates heat-shock response and prion propagation

Cellular and Molecular Life Sciences

2017 Hsp70 is a highly conserved chaperone that in addition to providing essential cellular functions and aiding in cell survival following exposure to a variety of stresses is also a key modulator of prion propagation. Hsp70 is composed of a nucleotide-binding domain (NBD) and substrate-binding domain (SBD).

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Systems impact of zinc chelation by the epipolythiodioxopiperazine dithiol gliotoxin in Aspergillus fumigatus: a new direction in natural product functionality

Metallomics

2018 The non-ribosomal peptide gliotoxin, which autoinduces its own biosynthesis, has potent anti-fungal activity, especially in the combined absence of the gliotoxin oxidoreductase GliT and bis-thiomethyltransferase GtmA. Dithiol gliotoxin (DTG) is a substrate for both of these enzymes. Herein we demonstrate that DTG chelates Zn2+ (m/z 424.94), rapidly chelates Zn2+ from Zn(4-(2-pyridylazo)-resorcinol) (Zn(PAR)2) and also inhibits a Zn2+-dependent alkaline phosphatase (AP).

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