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Alan Hargreaves

Associate Professor

School of Science & Technology

Staff Group(s)
Bioscience

Role

Dr Hargreaves is the Module Leader for the Neurotoxity and Neuroscience module. He teaches on the modules Cell Signalling and Cancer and Research Methods and IT. Dr Hargreaves is the Chair of the College Research Ethics Committee.

Research areas

Areas of research interest include mammalian transglutaminases and proteomic analysis of neurotoxin-treated differentiating neural cell lines.

  • Purification and characterisation of mammalian transglutaminases: A PhD project is currently underway to develop novel approaches to the purification of tissue transglutaminase from liver and brain tissue. This follows on from a recently completed PhD project, in which two forms of TG2 were detected in porcine brain and rodent cell lines, one of normal size (ca. 80 kDa) and the major form being lower than expected in molecular weight (ca. 55 kDa). The former was associated with mitochondria and the letter was the predominant form in the cytosol. Evidence suggests that the 50 kDa form is a truncated isoform of TG2 resulting from differential splicing. A novel method has now been developed to purify TG2 from liver and this will be applied to the purification of the truncated isoform in found porcine brain. This will allow studies of the kinetic properties of the short isoform with particular emphasis on its potential role as a toxicity target in certain chemically induced neuropathies.
  • Proteomic analysis of neurotoxin-treated differentiating neural cell lines: This project aims to provide identification of novel markers of toxicity and involves a number of toxins of interest, including the organophosphate phenyl saligenin phosphate, the sheep dip pesticides diazinon and cypermethrin, the PD inducing agent MPTP and heavy metals such as methyl mercury chloride, with PhD students currently working on the last two subject areas. The main approach is to study mechanisms of toxicity at sub-lethal concentrations in differentiating cell lines representative of neuronal and glial phenotypes. End points for cell viability and differentiation include MTT reduction and neurite outgrowth, respectively. A range of potential molecular markers are being analysed in a targetted proteomic approach (e.g. Western blotting analysis of cytoskeletal proteins and cell signalling pathways involved in their regulation), whereas 2D-PAGE and MALDI-TOF approaches are being used to identify other changes. He has continued to collaborate with colleagues both internally and at the University of Derby, on the application of targetted and non-targetted proteomic approaches to the identification of biomarkers of toxicity, stress and food contamination. In the latter case he is a co-investigator (with Professor EE Billett) on a FSA-funded project to detect molecular markers in certain meat products.

Research fellows:

  • Luigi de Girolamo
  • Lyndsay Durose
  • Wayne Harris

Research students:

  • Florence Burte
  • Shakthi Dookie
  • Muhammad Afzal Javed
  • Michelle Lawton
  • David Munoz

Opportunities to carry out postgraduate research towards an MPhil / PhD or MSc by research exist in all the areas identified above and in associated interdisciplinary areas. Further information may be obtained from the NTU Graduate School.

External activity

  • Member of the Biochemical Society
  • External Examiner for PhD theses, Universidad Autónoma de Madrid, (2005-2006)
  • External Examiner for PhD theses, Aston University, (2005-2006)
  • Invited Lecturer for “Cryopreservation in Support of the Conservation of European Plant Genetic Resources” International workshop, Catholic University of Leuven, Belgium, (2005)
  • Invited Lecturer for Workshop on Protein Cross-linking in Neuronal Inclusions, Debrecen, Hungary, (2003)
  • Invited Lecturer on the use of cytoskeletal proteins as markers of successful cryopreservation and practical sessions on the application of western blotting techniques using anti-cytoskeleton antibodies to monitor cryopreservation procedures.

Sponsors and collaborators

Current and recent research is being conducted with the collaboration, funding and / or support of:

University collaborations include Universidad Autónoma de Madrid, John Innes Institute, University of Liverpool, University of Thessaloniki, University of Leicester and Aston University.

Research funding in the period since 2002 includes:

  • Effects of sheep dip pesticides on differentiating nerve cells: Identification of novel markers of toxicity, A Hargreaves, J Flaskos and M Sachana, DEFRA VM02300 (2004 to 2006), £158,751.
  • Establishing cryopreservation methods for conserving European plant germplasm collections, A Hargreaves, PLR Bonner and PT Lynch, EU Framework V (2002 to 2005), £51,400.

Publications

Selected publications

  • Effects of sub-lethal neurite outgrowth inhibitory concentrations of chlorpyrifos oxon on cytoskeletal proteins and acetylcholinesterase. Harris W, Flaskos J, Hargreaves AJ, Sachana M and Nikolaidis E, Toxicology and Applied Pharmacology, 2011, 256, 330-336
  • Fipronil interferes with the differentiation of mouse N2a neuroblastoma cells. Harris W, Flaskos J, Hargreaves AJ, Sidiropoulou E, Sachana M et al, Toxicology Letters, 2011, 201 (1), 86-91
  • An extracellular transglutaminase is required for apple pollen tube growth.  Di Sandro A, Del Duca S, Verderio E, Hargreaves AJ, Scarpellini A, Cai G, Cresti M, Faleri C, Iorio RA, Hirose S, Furutani Y, Coutts IG, Griffin M, Bonner PL, Serafini-Fracassini D, Biochem.J, 2010, 429 (2), 261-271
  • Diazinon oxon affects the differentiation of mouse N2a neuroblastoma cells. Sidiropoulou E, Sachana M, Flaskos J, Harris W, Hargreaves AJ, Woldehiwet Z, Archives In Toxicology, 2009, 83 (4), 373-380
  • Proteomic analysis of differentiating neuroblastoma cells treated with sub-lethal neurite inhibitory concentrations of diazinon: Identification of novel biomarkers of effect. Harris W, Sachana M, Flaskos J, Hargreaves AJ, Toxicology And Applied Pharmacology, 2009, 240 (2), 159-165

For full list click 'Go to Alan Hargreaves publications' link above.

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