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Faculties & Departments
Department of Biology
Dr. Gary Jones
Head of Laboratory
Yeast Genetics Laboratory
- Dr. Gary Jones
- Tel: (353-1) 708 3839; Fax: (353-1) 708 3845
- e-mail: gary.jones@nuim.ie
Head of Laboratory
Gary Jones, BSc, PhD (Liverpool)
Research Interests
In 1982 the term prion was first coined by Stanley Prusiner to describe the nature of the scrapie infective agent. A prion is an infectious protein. It is a transmissible amyloid form of a cellular protein that replicates by converting the native protein into the same abnormal prion form. Prion and amyloid diseases of humans include Creutzfeld Jacob disease, Alzheimer's disease, Huntington disease and Type II diabetes. Much research has focused on understanding the mechanisms by which prions and amyloid arise and are maintained within an organism. In 1994 Reed Wickner proposed that the genetic behaviour of the Saccharomyces cerevisiae non-mendelian elements [ PSI + ] and [ URE3 ] could be explained if they were prions of the Sup35 and Ure2 proteins respectively. Since then much evidence has accumulated to support this proposal. The fact that prions exist in yeast provides an ideal environment for detailed genetic analysis of factors affecting prion propagation and maintenance.
Sup35p is a S. cerevisiae protein involved in termination of translation. In a state referred to as [ PSI + ], a significant portion of the Sup35 protein in the cell coalesces into nonfunctional, self-propagating, amyloid-like polymers. Thus, yeast strains that are [ PSI + ] show increased levels of nonsense suppression. We can monitor the presence of the prion in our yeast strains by a simple colour assay (figure 1). Once present, [ PSI + ] propagates by recruitment of the soluble form of Sup35p into the aggregate in a manner analogous to that of mammalian prions. A search for genetic factors affecting propagation and maintenance of [ PSI + ] has identified an essential role for molecular chaperones, namely Hsp70 and Hsp104. We have recently shown the importance of the Hsp70 ATPase domain in prion propagation and emphasised how the regulation of the Hsp70 ATPase cycle is essential for efficient prion propagation.
Our research aims at deciphering the complex relationship that exists between protein chaperones and prion/amyloid maintenance in yeast. The fact that chaperone complexes are extremely well conserved from yeast to higher eukaryotes means that our findings may be directly relevant to our understanding of prion and amyloid diseases in humans.
Figure 1- Monitoring the [PSI+] prion by a simple colour assay. The presence of the prion allows translation readthrough of an aberrant stop codon in the ADE2 gene. The consequence of this is the prion containing cells are white and cells lacking prions are red.
Laboratory Personnel
Postgraduate students
- Naushaba Hasin October 2009-
- Stephen Hammel October 2010-
Postdoctoral opportunities
Follow this link for current available postdoctoral positions in our lab.
Postgraduate opportunities
Follow this link for current available postgraduate positions in our lab.
Funding Sources
Current project grants
June 2008- June 2011. "Defining the mechanism of how a drug cures prions" Science Foundation Ireland, Research Frontiers Programme, €209,250.
Oct 2007- Oct 2010, IRCSET postgraduate scholarship awarded to Ms Ciara Moran- €72,009.
June 2007- June 2010, "Biochemical analysis of Hsp70 mutants that suppress prion propagation" Science Foundation Ireland, Research Frontiers Programme, €222,466.
Oct 2006- Oct 2009, "Effects of mutant Hsp70 species on mammalian prion propagation" Irish Health Research Board, €292,935.
Previous project grants
Oct 2004- Oct 2007, "Hsp70's Role in Amyloid Propagation" Irish Health Research Board, €189,048.
Mar 2005- Mar 2007, "Identification of potential prion proteins in plants" Marie Curie International Reintegration Fellowship (EU) €80,000.
June 2005- July 2006, "A genetic approach to investigate the interaction between a protein disaggregase and a prion" Science Foundation Ireland, Research Frontiers Award, €86,640.
Current Collaborations
Marc Blondel (Brest School of Medicine, France)- Mode of action of how drugs cure prions
Mario Fares (Trinity College Dublin, Ireland)- Evolution of molecular chaperones
Sarah Perrett (Chinese Academy of Sciences, Beijing)- Role of Hsp70 chaperone machinery in prion propagation
Mark Rogers (University College Dublin, Ireland)- Hsp70 and mammalian prion propagation
Elizabeth Vierling (University of Arizona, USA)- Investigating plant chaperone function in a yeast based system
Recent Publications
- E. Guinan and G. W. Jones (2009). The role of Hsp70 chaperone machinery in yeast prion propagation. Protein and Peptide Letters, Protein Pept. Lett. 2009;16(6):583-6.
- H. Zhang, H. M. Loovers, L.Q. Xu, M. Wang, P. J .E. Rowling, L. S. Itzhaki, W. Gong, J. M. Zhou, G. W. Jones and S. Perrett (2009). Alcohol oxidase (AOX1) from Pichia pastoris is a novel inhibitor of prion propagation and a potential ATPase. Molecular Microbiology 71(3): 702-716.
- S. Perrett and G.W. Jones (2008). Insights into prion propagation. Current Opinion in Structural Biology. 18(1):52-9.
- H. Y. Lian, H. Zhang, Z. R. Zhang, H. M. Loovers, G. W. Jones, P. J. E. Rowling, L. S. Itzhaki, J. M. Zhou and S. Perrett (2007). Hsp40 interacts directly with the native C-terminal region of the yeast prion protein Ure2 and inhibits formation of amyloid-like fibrils. Journal of Biological Chemistry 282(16):11931-40.
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H. M. Loovers, E. Guinan and G. W. Jones (2007). Importance of Hsp70 ATPase domain in prion propagation. Genetics 175(2): 621-630.
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H. Y. Lian, Y. Jiang, H. Zhang, G. W Jones, S. Perrett (2006). The Yeast Prion Protein Ure2: Structure, Function and Folding. BBA - Proteins and Proteomics. 1764: 535- 545.
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G. W. Jones and M. F. Tuite (2005) Chaperoning prions: the cellular machinery for propagating an infectious protein? BioEssays 27 : 823-832.
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G. Jones, Y. Song, S. Chung and D. C. Masison (2004). Propagation of yeast [ PSI + ] prion impaired by factors that regulate Hsp70 substrate binding. Mol. Cell. Biol . 24(9) 3928-3937.
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G. Jung and G. W. Jones (2003). Yeast Prions. J. of Biol. Macromol. 3 (2) 41-46.
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G. W. Jones, Y. Song and D. C. Masison (2003) Deletion of yeast HSP70 chaperone SSB causes hypersensitivity to guanidine toxicity and curing of [ PSI + ] prion by increasing guanidine uptake. Mol. Gen. & Genomics 269 : 304-311.
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G. W. Jones and D. C. Masison (2003) S. cerevisiae Hsp70 mutations affect [ PSI + ] prion propagation and cell growth differently and implicate Hsp40 and TPR co-chaperones in impairment of [ PSI + ]. Genetics 163 : 495-506.
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G. Jung, G. Jones and D. C. Masison (2002) Amino acid residue of yeast Hsp104 chaperone critical for prion curing by guanidine and for prion propagation. Proc Natl Acad Sci U S A, 99 (15) 9936-41.
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G. Jung, G. Jones, R. D. Wegrzyn and D. C. Masison (2000) A role for cytosolic Hsp70 in yeast [ PSI + ] prion propagation and [ PSI + ] as a cellular stress. Genetics 156 p559-570.
Other publications:
- D. I. O'Connor and G. W. Jones (2006) Chaperoning prions: the story unfolds. BIO TECH international; February/March issue, 18: 6-10.
- P. W. Piper, G. W. Jones, D. Bringloe, N. Harris, M. MacLean and M. Mollapour (2002) The cause of the shortened replicative life span in prohibitin mutants of yeast appears to be defective mitochondrial morphology and segregation in old mother cells. Aging Cell 1: 149- 157.
- G. W. Jones, Hooley. P, Farrington. S. M, Shawcross. S. G and Strike. P (1999) Cloning and characterisation of the sagA gene of Aspergillus nidulans: a gene which affects sensitivity to DNA-damaging agents. Mol. & Gen. Genet. 261: 251- 258.
- G. W. Jones, S. H. Reed and R. Waters (1997) Characterisation of the rad14-2 mutant of Saccharomyces cerevisiae: implications for photoproduct recognition by the Rad14 protein. Yeast 13: 31- 36.
- L. A. Iwanejko, Cotton. C . M, Jones. G. W, Strike. P and Tomsett. A. B (1996) Cloning and characterisation of nuvA, an Aspergillus nidulans gene involved in DNA repair and recombination. Microbiology 142: 505- 515.