Professor David Sheehan
 

Professor David Sheehan
Associate Professor in Biochemistry
Principal Investigator, Environmental Research Institute, University College Cork

Contact Information
Proteomic Research Laboratory
Department of Biochemistry
University College Cork
Lee Maltings Prospect Row,
Mardyke,
Cork

Email:  Professor David Sheehan
Tel:     +353 21 490 4207
Fax:    +353 21 427 4034

Education
BSc (1H), 1980, Biochemistry, UCC
Ph.D, 1985, Trinity College Dublin

 
Teaching

I teach Introductory Biochemistry and courses at Science III and IV level with an emphasis on Proteins (especially enzymes), their structure and study. I also have a strong interest in biophysical methods for studying proteins.

 

An outline of my courses and all courses taught by staff in the Department of Biochemistry are available in UCC's Book of Modules.
My courses are all available to registered students on Blackboard.
An electronic version of my teaching portfolio is available here.
Find my textbook Physical Biochemistry: Principles and Applications (2000; Wileys) here. The Second Edition will be published in early 2009.

 
 
 
 
Additional Links
I am currently a committee member of the British Biophysical Society and supervise PhD students funded by Irish Research Council for Science, Engineering and Technology (IRCSET) and the Higher Education Authority (HEA).
 
 
 
Research Interests.
Developments in methodologies such as protein mass spectrometry and two-dimensional electrophoresis promise much more routine and systematic identification of important aspects of protein structure like post-translational modification which are often fundamental to understanding individual protein function. My principal research approaches which include enzymology, biophysical methods, enzyme kinetics, protein purification, chemistry and structure equip me to participate in this development into the near future and beyond.
 
Current Research Projects:
1.     Studies on glutathione transferases (GSTs).
GSTs are important in removing foreign and potentially toxic chemicals (xenobiotics) from cells by catalysing conjugation to glutathione and play a major role in non-catalytic binding of endogenous and xenobiotic ligands. As such they are of major pharmacological and environmental importance.

My group has pioneered the study of these enzymes from fungi in order to shed light on the evolution of the main GST classes. We have now purified GSTs from a range of species and this has revealed that fungal enzymes are structurally related to the Theta class. Moreover, we have purified one of the largest GSTs ever isolated from the non-Saccharomyces yeast, Yarrowia lipolytica, which is a component of the elongation system of protein biosynthesis EF1Bγ.

A second activity has focused on GSTs of Mytilus edulis, a popular bioindicator organism, with a view to their potential use as indices of exposure to chemical pollution. We have extended these investigations by biochemically characterising mussel GSTs, assessing levels of other antioxidant enzymes and heat shock proteins in response to pollution and investigating natural biological variation in antioxidant enzyme levels.
 
         Related Publications
  • Dowd, C.A., Buckley, C.M. and Sheehan, D.
    Glutathione S-transferases of the white rot fungus, Phanerochaete chrysosporium. (1997)
    Biochemical Journal. 324, 243-248
  • Foley, V. and Sheehan, D.
    Glutathione S-transferases of the yeast Yarrowia lipolytica have unusually large molecular mass (1998)
    Biochemical Journal. 333, 839-845.
  • Dowd, C. and Sheehan, D.
    Variable expression of glutathione S-transferase isoenzymes in the fungus Mucor circinelloides. (1999)
    FEMS Microbiol. Lett.s 170, 13-17.
  • Sheehan, D. and Power, A.
    Effects of seasonality on xenobiotic and antioxidant defence mechanisms of bivalve molluscs. (1999)
    Comparative Biochemistry and Physiology. 123, 3-9.
  • Sheehan, D., Meade, G., Foley, V. and Dowd, C.
    Structure, function and evolution of glutathione S-transferases: Implications for the classification of non-mammalian members of an ancient enzyme superfamily. (2001)
    Biochemical Journal. 360, 1-16.
  • McGoldrick, S., O’Sullivan, S.M. and Sheehan, D.
    Glutathione transferase-like proteins encoded in genomes of yeasts and fungi: Insights into evolution of a multifunctional protein superfamily. (2005)
    FEMS Microbiol. Lett.s
    . 242, 1-12.
  • McGoldrick, S., McCarthy, T.V. and Sheehan, D.
    The 110 kDa glutathione transferase of Yarrowia lipolytica is encoded by a homologue of the TEF3 gene from Saccharomyces cerevisiae: Cloning, expression and homology modeling of the recombinant protein. (2005)
    Biochem. Biophys. Res. Commun. 337, 1125-1132.
  • O’Sullivan, S.M., McCarthy, R., Vargo, M., Coleman, R., Sheehan, D. (2006) Labelling cysteines-17 (subunit 1) of rat kidney Alpha class glutathione transferases with 2,3,5,6-tetrachloro-1, 4-benzoquinone: Highly correlated effects on both glutathione conjugation and tryptophan-20 intrinsic fluorescence. Biochemical Pharmacology 71, 1629-1636.
 
2.     In vitro toxicology with molluscs.
We successfully developed tissue culture methods suitable for the Pacific Oyster, Crassostrea gigas. The objective of this work is to develop in vitro toxicological tools to supplement in vivo toxicology work with mussels. This was extended in the VITOX project in collaboration with Dublin Institute of Technology.
 
         Related Publications
  • Sheehan D.
    Applications of in vitro techniques in studies of biomarkers and ecotoxicology.
    In In Vitro Methods in Aquatic Toxicology (C. Mothersill and B. Austin, eds.). (2004)
    Springer-Verlag pp.55-76.
  • Ní Shúilleabháin, S., Mothersill, C., Sheehan, D., O'Brien, N.M., O'Halloran, J., Van Pelt, F. and Davoren, M.
    In vitro cytotoxicity testing of three zinc metal salts using established fish cell lines. (2004)
    Toxicology In Vitro. 18, 367-376.
  • Davoren, M., Ní Shúilleabháin, Hartl, MG.J.,S., Sheehan, D., O'Brien, N.M., O' Halloran, J., Van Pelt, F.N.A.M. and Mothersill, C.
    Assessing the potential of fish cell lines as tools for the cytotoxicity testing of estuarine sediment aqueous elutriates. (2005)
    Toxicology in Vitro. 19 , 421-431.
  • Davoren, M., Ní Shúilleabháin, S., O' Halloran, J., Hartl, M.G.J., Sheehan, D., O'Brien, N.M.,Van Pelt, F.N.A.M., and Mothersill, C.
    A test battery approach for the ecotoxicological evaluation of estuarine sediments. (2005)
    Ecotoxicology. 14, 741-755.
  • Ní Shúilleabháin, S., Mothersill, C., Sheehan, D., O'Brien, N.M., O' Halloran, J., Van Pelt, F.N.A.M., Kilemade, M. and Davoren, M.
    Cellular responses in primary epidermal cultures from rainbow trout exposed to zinc chloride. (2006)
    Ecotoxicology and Environmental Safety. 65, 332-334.
 
3.     Proteomics in environmental monitoring.

We are applying 2-D SDS PAGE to molluscs exposed to environmental chemical pollutants in field-sampled mussels, in mussels deliberately exposed to pro-oxidants and in sediment-challenged clams. A separate project involves developing 2-D SDS PAGE methods for identifying proteins especially targeted by oxidative stress. This focuses on detection of carbonylated and glutathionylated proteins as well as effects on thiol and disulphide status. Recently, in collaboration with Tyndall Natl Laboratory, we have become interested in study of redox effects of nanoparticles.

 
         Related Publications
  • McDonagh, B. and Sheehan, D. (2008) Effects of oxidative stress on protein thiols and disulphides in Mytilus edulis revealed by proteomics: Actin and protein disulphide isomerase are redox targets. Marine Environmental Research 66, 193-195.

  • McDonagh, B. and Sheehan, D. (2007) Effect of oxidative stress on protein thiols in the blue mussel, Mytilus edulis: Proteomic identification of target proteins. Proteomics, 7, 3395-3403.

  • Chora, S., McDonagh, B., Sheehan, D., Starita-Geribaldi, M., Romeo, M and Bebianno, M.J. (2008) Ubiquitination and carbonylation as markers of oxidative stress in Ruditapes decussatus. Marine Environmental Research 66, 95-97.

  • Sheehan D. (2007) Potential of proteomics in environmental health. Reviews on Environmental Health 22, 175-194.

  • Prevodnik, A., Gardeström, J., Lilja, K., Elfwing, T., McDonagh B., Petrovic, N., Tedengren, M., Sheehan, D. and Bollner, T. (2007) Oxidative stress in response to xenobiotics in the blue mussel Mytilus edulis L: Evidence for variation along a natural salinity gradient of the Baltic Sea. Aquatic Toxicology, 82, 63-71.

  • Dowling, V.A. and Sheehan D. (2006) Proteomics as a route to identification of toxicity targets in ecotoxicology Proteomics 6, 5597-5604.

  • Dowling, V., Hoarau, P., Romeo, M., O’Halloran, J., F. van Pelt, F. N. A. M., O’Brien, N.M., and Sheehan, D. (2006) Protein carbonylation and heat shock response in Ruditapes decussatus following p,p'-dichlorodiphenyldichloroethylene (DDE) exposure: a proteomic approach reveals DDE causes oxidative stress. Aquatic Toxicology 77, 11-18.

 

Graph

 
4.     Redox Proteomics.
We are interested in application and development of methods for detection of lesions introduced into proteins both under conditions of oxidative stress but also during redox signalling. This now includes gel-based and gel-free methods. We are especially interested in using the spontaneously hypertensive rat as a model for study of redox lesions in kidney.
 
         Related Publications
  • Tyther, R., Ahmeda, A., Johns, E. and Sheehan D. (2008) Protein carbonylation in kidney medulla of the spontaneously hypertensive rat. Proteomics Clin. Invest. IN PRESS

  • Sheehan D. and McDonagh B. (2008) Bivalves and oxidative stress: A proteomics approach. Invertebrate Survival Journal 5, 110-123.

  • Tyther, R., Ahmed, M., Johns, E. and Sheehan, D. (2007) Proteomic identification of nitrosylated proteins in hypertensive rat kidneys. Proteomics 7, 4555-4564

  • Sheehan D. (2006) Detection of redox-based modification in two dimensional electrophoresis proteomic separations. Biochemical and Biophysical Research Communications 349 , 455-462.

 
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5.     Nanotoxicology.
Nanomaterials represent a major potential toxicological threat because of their ability to cross biological barriers such as the intestine, blood-brain barrier and even the cell membrane. In collaboration with Drs. Daniela Iacopino and Hugh Doyle (Tyndall National Laboratory) and Profs. Gareth Redmond and Ken Dawson (UCD) we are studying effects of nanoparticles on the redox status of a variety of biological systems.
 
         Related Publications
  • Hu, W., Keane, C., Doyle, H., Iacopino, D., Redmond, G., and Sheehan, D. (2008) Antioxidant effects of gold nanoparticles revealed by study of protein thiols in Escherichia coli. Nanotoxicology SUBMITTED

  • Tedesco, S., Doyle, H., Redmand, G. and Sheehan, D. (2008) Gold nanoparticles effects on mussel Mytilus edulis: A proteomic approach. Marine Environmental Research 66, 131-133.

 
Current Research Grants
  • 2008 €72,000 Irish Research Council for Science Engineering and Technology PhD grant Proteomics approach to oxidative stress in Daphnia magna.

  • 2007 Invited participant in COST action FA0603 Plant Proteomics in Europe .

  • 2006 €40,000 Environmental Protection Agency. A novel green technology for environmental remediation of chloroaromatic contaminants. Joint with Dr Marcel Jansen (ZEPS, UCC).

  • 2006 €72,009 Irish Research Council for Science Engineering and Technology PhD grant Redox proteomic investigation of the mussel Mytilus edulis in ecotoxicology .

  • 2005 €150,000 Irish Health Research Board grant; Dental Erosion in Irish Teenagers: An Epidemiological and Laboratory Investigation. Collaboration with Dr Helen Whelton, Dental School, UCC.

 
Publications and Editorial Activities

Main author of over 70 refereed papers, over 30 other publications and 4 books.
  1. Sheehan, D. (Editor) (1997)
    Bioremediation Protocols
    Volume 2 in series Methods in Biotechnology
    (Humana Press, series editor Prof John Walker). 339pp.
  2. Sheehan, D. (2000)
    Physical Biochemistry: Principles and Applications

    John Wiley & Sons Ltd. London . 350pp.
  3. Sheehan, D. (2009)
    Physical Biochemistry: Principles and Applications
    ,
    John Wiley & Sons Ltd. London.
    (350pp; http://www.wiley.co.uk ).
    Second edition published in Spring 2009.
  4. Sheehan, D. (Editor) (2009)
    Two Dimensional Electrophoresis Protocols,
    (Humana Press, series editor Prof John Walker).
    (450pp.; http://www.humanapress.com).
A selection of Professor David Sheehan's book jackets

 

Would you like to view my Full Publication List?

Then, please click here for a full list of all my publications to March 2010.

For the past five years, I have acted as referee for 40 peer-reviewed journals including:

  • The Biochemical Journal;
  • Biochimica et Biophysica Acta;
  • Archives of Biochemistry and Biophysics;
  • Environmental Pollution;
  • Archives of Environmental Contamination and Toxicology;
  • Science of the Total Environment;
  • European Journal of Biochemistry Biotechnology and Applied Biochemistry;
  • International Journal of Biochemistry and Cell Biology;
  • Environmental Toxicology and Chemistry.

1999 - Date
Editorial Advisor, Biochemical Journal

2002 - Date
Member of Editorial Board Essays in Biochemistry (Portland Press)

2006 - Date
Member of Editorial Board Research Journal of Biological Sciences (Medwell)

2008 - Date
Member of Editorial Board Drug Testing and Analysis (Wiley-Blackwell)

 

Recently reviewed grants for: Italian Ministry of Universities; Biotechnology and Biological Sciences Research Council (UK); Wellcome Trust (UK); Natural and Environmental Research Council (UK), Association for International Cancer Research (UK), the Alzheimer's Association (USA), the Alzheimer's Society (UK), the Nuffield Trust (UK).
 
Postgraduate Research Supervision

Research Group
 
Sara Tedesco, Phd student, Department of Biochemistry, UCC

Sara Tedesco , MSc

PhD student
(Irish Research Council for Science Engineering and Technology EMBARK studentship).

 

Project
Redox proteomic investigation of the mussel Mytilus edulis in ecotoxicology

 
Publications
  • Gorbi S., Pellegrini D., Tedesco S., Regoli F. (2004).
    Antioxidant efficiency and detoxification enzymes in spotted dogfish Scyliorhinus canicula.
    Mar. Environ. Res. 58: 293-297

  • Regoli F., Gorbi S., Machella N., Tedesco S., Benedetti M., Bocchetti R., Notti A., Fattorini D., Piva F., Principato G. (2005).
    Pro-oxidant effects of extremely low frequency electromagnetic fields in the land snail Helix aspersa.
    Free Radical Biology & Medicine 39: 1620-1628.

  • Regoli F. , Gorbi S., Fattorini D., Tedesco S., Notti A., Machella N., Bocchetti R., Benedetti M., Piva F. (2006).
    Use of the Land Snail Helix aspersa as Sentinel Organism for Monitoring Ecotoxicologic Effects of Urban Pollution: An integrated Approach.
    Environmental Health Perspectives 114: 63-69

  • Tedesco, S., Doyle, H., Redmond, G. and Sheehan, D. (2007).
    Gold Nanoparticles Effects on Mussel Mytilus Edulis: A Proteomic Approach.
    Marine Environmental Research. IN PRESS.
 
Hu Wentao

Hu Wentao, MSc

PhD student

 

Project
Novel selection approaches in redox proteomics

Career History
Wentao completed a B.Sc. in Material Science, SUES, Shanghai, China. He came to Ireland in 2006 to complete an MSc in Applied Science (Biotechnology).

 

 
Hu Wentao

Louis-Charles Rainville, MSc

PhD student

 

Project
Proteomics approach to oxidative stress in Daphnia magna

Career History

Louis-Charles is a Canadian student from Quebec Province. He holds a BSc in Biochemistry and Biotechnologies and a MSc in oceanography from the University of Quebec (ISMER,UQAR), during which he started specialising in ecotoxicology by exploring multixenobiotic resistance in marine algae.. He has a strong interest in proteins and biophysics, but wants to apply this mostly to the environmental field. He is a lover of science, philosophy and knowledge in general. He says, you'll generally see him in a lot of places as he tends to get involved a lot in university life! His PhD research topic is Proteomics approach to oxidative stress in Daphnia magna.

 
Outreach Activities
Our laboratory is actively involved in promoting Science at primary and secondary school levels. We regularly accept transition year students as part of their school work experience. We regularly host young scientists from EU countries for short training internships in proteomics.
 

 

©2009 Department of Biochemistry, University College Cork, Ireland.