Professor Gary Jones, Director of Research

Professor Gary Jones

Director of Research

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.

Current Teaching

  • PhD and MSc (by research) supervision

Research Interests

Current specific research projects are focused on deciphering the effects of post-translation modification [phosphorylation and acetylation] of Hsp70 on cellular function. Hsp70 is a highly conserved protein that is involved in a variety of essential cellular functions, for example assisting other proteins to obtain a functional three-dimensional structure. In this regard Hsp70 is referred to a chaperone. A number of devastating human neurodegenerative diseases such as Alzheimer’s and Parkinson’s are caused by improper protein folding, and are indeed classified as protein mis-folding diseases. Hsp70 plays a central role in preventing protein mis-folding and hence is a potential therapeutic target for such diseases. However, with Hsp70’s involvement in such diverse and important cellular processes, targeting this protein directly can be problematic due to unintended side effects. Therefore we are taking a novel approach and aiming to understand the effects of altering Hsp70 function through protein modification such as phosphorylation and identifying the proteins that carry out these modifications. An example of the impact of such an approach was the discovery of a new role for Hsp70 in cell cycle control through phosphorylation of the protein (Truman et al. 2012), which provides a potential new therapeutic strategy for certain cancers. This work is carried out in collaboration with Dr. Andrew Truman [University of North Carolina, Charlotte].

Other ongoing projects are focused on developing new therapeutic strategies against the opportunistic pathogen Aspergillus fumigatus. This fungus is responsible for a significant number of deaths worldwide in immunocompromised individuals [eg, patients undergoing chemotherapy]. The development of new antifungal treatments is a major global concern. In collaboration with Professor Sean Doyle [Maynooth University] we are taking a novel approach of understanding and utilizing unique aspects A. fumigatus endogenous biochemistry to identify new molecular therapeutic targets. Specifically we focus on understanding the molecular stages of the production of secondary metabolite mycotoxin gliotoxin. We have identified and characterized how the fungus protects itself against its own toxin [Schrettl et al. 2010] and we are now deciphering how the toxin interacts with other cellular metabolic processes [Dolan et al. 2014, Owens et al 2015, Smith et al. 2016], which may allow us to manipulate gliotoxin production in vivo as a new therapeutic strategy for this hard to treat pathogenic fungus.

Professor Gary Jones, Director of Research

Ask Me About

  1. Microbiology
  2. Cellular stress
  3. Genetics
  4. Molecular biology
  5. Biomedical sciences

Selected Outputs

  • Xu L; Nitika; Hasin N; Cuskelly DD; Wolfgeher D; Doyle S; Moynagh P; Perrett S; Jones GW; Truman AW (In press) Rapid deacetylation of yeast Hsp70 mediates the cellular response to heat stress. Scientific Reports, 9 (1),

    https://doi.org/10.1038/s41598-019-52545-3

  • Downes SG; Owens RA; Walshe K; Fitzpatrick DA; Dorey A; Jones GW; Doyle S (2023) Gliotoxin-mediated bacterial growth inhibition is caused by specific metal ion depletion. Scientific Reports, 13 pp. 1-20.

    https://doi.org/10.1038/s41598-023-43300-w

  • Downes SG; Doyle S; Jones GW; Owens RA (2023) Gliotoxin and related metabolites as zinc chelators: implications and exploitation to overcome antimicrobial resistance. Essays in Biochemistry, pp. 1-12.

    https://doi.org/10.1042/ebc20220222

  • Doyle S; Cuskelly DD; Conlon N; Fitzpatrick DA; Gilmartin CB; Dix SH; Jones GW (2022) A Single Aspergillus fumigatus Gene Enables Ergothioneine Biosynthesis and Secretion by Saccharomyces cerevisiae. International Journal of Molecular Sciences, 23 (18), pp. 1-22.

    https://doi.org/10.3390/ijms231810832

  • Traynor AM; Owens RA; Coughlin CM; Holton MC; Jones GW; Calera JA; Doyle S (2021) At the metal–metabolite interface in Aspergillus fumigatus: towards untangling the intersecting roles of zinc and gliotoxin. Microbiology, 167 (11), pp. 1-15.

    https://doi.org/10.1099/mic.0.001106

  • Xu L; Zhang H; Cuskelly DD; Doyle S; Perrett S; Jones GW (2021) Mutational analysis of the Hsp70 substrate‐binding domain: Correlating molecular‐level changes with in vivo function. Molecular Microbiology

    https://doi.org/10.1111/mmi.14671

  • Gong W; Hu W; Xu L; Wu H; Wu S; Zhang H; Wang J; Jones G; Perrett S (2018) The C-terminal GGAP motif of Hsp70 mediates substrate recognition and stress response in yeast. Journal of Biological Chemistry

    https://doi.org/10.1074/jbc.RA118.002691

  • Saleh AA; Jones GW; Tinley FC; Delaney SF; Alabbadi SH; Fenlon K; Doyle S; Owens RA (2018) Systems impact of zinc chelation by the epipolythiodioxopiperazine dithiol gliotoxin in Aspergillus fumigatus: A new direction in natural product functionality. Metallomics, 10 (6), pp. 854-866.

    https://doi.org/10.1039/c8mt00052b

  • Xu L; Gong W; Cusack SA; Wu H; Loovers HM; Zhang H; Perrett S; Jones GW (2018) The β6/β7 region of the Hsp70 substrate-binding domain mediates heat-shock response and prion propagation. Cellular and Molecular Life Sciences, 75 (8), pp. 1445-1459.

    https://doi.org/10.1007/s00018-017-2698-3

  • Doyle S; Jones G; Dolan SK (2017) Dysregulated gliotoxin biosynthesis attenuates the production of unrelated biosynthetic gene cluster-encoded metabolites in Aspergillus fumigatus. Fungal Biology

    https://doi.org/10.1016/j.funbio.2017.12.007

  • Dolan SK; Bock T; Hering V; Owens RA; Jones GW; Blankenfeldt W; Doyle S (2017) Structural, mechanistic and functional insight into gliotoxin bis-thiomethylation in Aspergillus fumigatus. Open Biology, 7 (2),

    https://doi.org/10.1098/rsob.160292

  • Sheridan KJ; Lechner BE; Keeffe GO; Keller MA; Werner ER; Lindner H; Jones GW; Haas H; Doyle S (2016) Ergothioneine Biosynthesis and Functionality in the Opportunistic Fungal Pathogen, Aspergillus fumigatus. Scientific Reports, 6

    https://doi.org/10.1038/srep35306

  • Smith EB; Dolan SK; Fitzpatrick DA; Doyle S; Jones GW (2016) Towards understanding the gliotoxin detoxification mechanism: in vivo thiomethylation protects yeast from gliotoxin cytotoxicity. Microbial Cell, 3 (3), pp. 120-125.

    https://doi.org/10.15698/mic2016.03.485

  • Owens RA; O’keeffe G; Smith EB; Dolan SK; Hammel S; Sheridan KJ; Fitzpatrick DA; Keane TM; Jones GW; Doyle S (2015) Interplay between gliotoxin resistance, secretion, and the methyl/methionine cycle in Aspergillus Fumigatus. Eukaryotic Cell, 14 (9), pp. 941-957.

    https://doi.org/10.1128/EC.00055-15

  • Dolan SK; O’Keeffe G; Jones GW; Doyle S (2015) Resistance is not futile: gliotoxin biosynthesis, functionality and utility. Trends in Microbiology, 23 (7), pp. 419-428.

    https://doi.org/10.1016/j.tim.2015.02.005

  • Hasin N; Cusack SA; Ali SS; Fitzpatrick DA; Jones GW (2014) Global transcript and phenotypic analysis of yeast cells expressing Ssa1, Ssa2, Ssa3 or Ssa4 as sole source of cytosolic Hsp70-Ssa chaperone activity. BMC Genomics, 15 (1),

    https://doi.org/10.1186/1471-2164-15-194

  • He J; Wang Y; Chang AK; Xu L; Wang N; Chong X; Li H; Zhang B; Jones GW; Song Y (2014) Myricetin Prevents Fibrillogenesis of Hen Egg White Lysozyme. Journal of Agricultural and Food Chemistry, 62 (39), pp. 9442-9449.

    https://doi.org/10.1021/jf5025449

  • Jones GW; Doyle S; Fitzpatrick DA (2014) The evolutionary history of the genes involved in the biosynthesis of the antioxidant ergothioneine. Gene, 549 (1), pp. 161-170.

    https://doi.org/10.1016/j.gene.2014.07.065

  • Dolan SK; Owens RA; O'Keeffe G; Hammel S; Fitzpatrick DA; Jones GW; Doyle S (2014) Regulation of nonribosomal peptide synthesis: Bis-thiomethylation attenuates gliotoxin biosynthesis in Aspergillus fumigatus. Chemistry and Biology, 21 (8), pp. 999-1012.

    https://doi.org/10.1016/j.chembiol.2014.07.006

  • Keane OM; Toft C; Carretero-Paulet L; Jones GW; Fares MA (2014) Preservation of genetic and regulatory robustness in ancient gene duplicates of Saccharomyces cerevisiae. Genome Research, 24 (11), pp. 1830-1841.

    https://doi.org/10.1101/gr.176792.114

  • Xu L-Q; Wu S; Buell AK; Cohen SIA; Chen L-J; Hu W-H; Cusack SA; Itzhaki LS; Zhang H; Knowles TPJ (2013) Influence of specific HSP70 domains on fibril formation of the yeast prion protein Ure2. Philosophical Transactions of the Royal Society B: Biological Sciences, 368 (1617), pp. 20110410-20110410.

    https://doi.org/10.1098/rstb.2011.0410

  • Truman AW; Kristjansdottir K; Wolfgeher D; Hasin N; Polier S; Zhang H; Perrett S; Prodromou C; Jones GW; Kron SJ (2012) CDK-Dependent Hsp70 Phosphorylation Controls G1 Cyclin Abundance and Cell-Cycle Progression. Cell, 151 (6), pp. 1308-1318.

    https://doi.org/10.1016/j.cell.2012.10.051

  • O’Hanlon KA; Margison GP; Hatch A; Fitzpatrick DA; Owens RA; Doyle S; Jones GW (2012) Molecular characterization of an adaptive response to alkylating agents in the opportunistic pathogen Aspergillus fumigatus. Nucleic Acids Research, 40 (16), pp. 7806-7820.

    https://doi.org/10.1093/nar/gks522