University of Dundee

Dr David Gray

Molecular Pharmacology and Compound Screening
Position: 
Head of Biology
Address: 
School of Life Sciences, University of Dundee, Dundee
Full Telephone: 
+44 (0) 1382 386247, int ext 86247
Email: 

Research

The Drug Discovery Unit (DDU) (est. 2006, see http://ddu.aegir.lifesci.dundee.ac.uk/) within the College of Life Sciences at Dundee has been created to respond to our perceived lack of capacity in the UK for early stage drug discovery in the academic sector. The DDU’s aim is to translate basic science into lead compounds to validate putative drug targets, to use as tools to investigate disease pathways and, when appropriate, advance to pre-clinical drug candidates. The DDU works to Biotech style philosophy and standards incorporating; dynamic, goal driven project management based on Target Product Profiles and Compound Selection Criteria. The DDU is the only fully operational and integrated drug discovery team within UK universities with the full range of disciplines including compound management, screening, molecular pharmacology/enzymology, medicinal chemistry, computational chemistry, DMPK and disease model capabilities, required to produce novel hit and lead candidates.

Since its inception the Unit has developed an international reputation as a leader in the growing academic drug discovery sector.

As Head of Biology within the Drug Discovery Unit (DDU),my role is to develop strategies for people, facilities, equipment and IT to allow the effective support of hit discovery, hits to leads and lead optimisation programs.

We currently support two broad areas, these being neglected diseases (malaria, leishmania, sleeping sickness, TB and Chagas’ disease) and innovative targets; a portfolio to translate new biological findings from Dundee and beyond.  We conduct assay development, small molecule screening and an extensive array of mechanism of action and other supporting biology to define and characterise small molecule tools suitable for use in primary biological research and drug discovery.

 

Teaching

Course coordinator BS32003 – Drug Discovery & Development
BS42004 – Advanced Modern Drug Discovery
M.Res Cancer Biology

Publications

1.    Identification of Novel Inhibitors of the Type I Interferon Induction Pathway Using Cell-Based High-Throughput Screening. Zoe O. Gage, Z.O, Vasoul, A., Gray, D.W., Randall, R.E. and Adamson, C.S. Journal of Biomolecular Screening 2016 doi 10.1177/1087057116656314.

2.    Development and Validation of a Novel Leishmania donovani Screening Cascade for High-Throughput Screening Using a Novel Axenic Assay with High Predictivity of Leishmanicidal Intracellular Activity. Nühs, A., De Rycker, M., Manthri, S., Comer, E., Scherer, C.A., Schreiber, S.L., Ioset J., and Gray, D.W. PLoS Negl Trop Dis. 2015 Sep; 9(9): e0004094.

3.    New Compound Sets Identified from High Throughput Phenotypic Screening Against Three Kinetoplastid Parasites: An Open Resource. Imanol Peña, M Pilar Manzano, Juan Cantizani, Albane Kessler, Julio Alonso-Padilla, Ana I Bardera, Emilio Alvarez, Gonzalo Colmenarejo, Ignacio Cotillo, Irene Roquero, Vanessa Barroso, Ana Rodriguez, David W Gray, Miguel Navarro, Vinod Kumar, Alexander Sherstnev, David H Drewry, James R Brown, Jose M Fiandor, J Julio Martin. Scientific Reports 03/2015; 5:8771. DOI:10.1038/srep08771

4.    Identification of Small Molecule Inhibitors of Pre-mRNA Splicing. Andrea Pawellek, Stuart McElroy, Timur Samatov, Lee Mitchell, Andrew Woodland, Ursula Ryder, David Gray, Reinhard Lührmann, Angus I Lamond. Journal of Biological Chemistry 10/2014; 290(10). DOI:10.1074/jbc.M114.590976

5.    High throughput chemical screening for anti-virulence developmental phenotypes in Trypanosoma brucei.  Macgregor, P., Ivens, A., Shave, S., Collie, I., Gray, D., Auer, M., Matthews, K. R. Jan-2014 In: Eukaryotic cell doi 10.1128/EC.00335-13

6.    Comparison of a high-throughput high-content intracellular Leishmania donovani assay with an axenic amastigote assay. De Rycker, M., Hallyburton, I., Thomas, J., Campbell, L., Wyllie, S., Joshi, D., Cameron, S., Gilbert, I. H., Wyatt, P. G., Frearson, J. A., Fairlamb, A. H. & Gray, D. W. Jul-2013 In : Antimicrobial Agents and Chemotherapy. 57, 7, p. 2913-2922, 10 p.

7.    Discovery of an allosteric inhibitor binding site in 3-oxo-acyl-ACP reductase from Pseudomonas aeruginosa. Cukier, C. D., Hope, A. G., Elamin, A. A., Moynie, L., Schnell, R., Schach, S., Kneuper, H., Singh, M., Naismith, J. H., Lindqvist, Y., Gray, D. W., Schneider, G.Seo-2013 In: ACS Chemical Biology, 8, (11), 2518-27

8.    A static-cidal assay for Trypanosoma brucei to aid hit prioritisation for progression into drug discovery programmes. De Rycker, M., O'Neill, S., Joshi, D., Campbell, L., Gray, D. W. & Fairlamb, A. H. 29-Nov-2012 In : PLoS Neglected Tropical Diseases. 6, 11, p. e1932

9.    Allosteric competitive inhibitors of the glucose-1-phosphate Thymidylyltransferase (RmlA) from Pseudomonas aeruginosa. Alphey, M. S., Pirrie, L., Torrie, L. S., Boulkeroua, W. A., Gardiner, M., Sarkar, A., Maringer, M., Oehlmann, W., Brenk, R., Scherman, M. S., McNeil, M., Rejzek, M., Field, R. A., Singh, M., Gray, D., Westwood, N. J. & Naismith, J. H. 2013 In : ACS Chemical Biology, 8, (2), 387-96

10.    Assessment of pseudomonas aeruginosa N-5,N-10-methylenetetrahydrofolate dehydrogenase - cyclohydrolase as a potential antibacterial drug target. Eadsforth, T. C., Gardiner, M., Maluf, F. V., McElroy, S., James, D., Frearson, J., Gray, D. & Hunter, W. N. 2012 In : PLoS ONE. 7, 4, p. -, 11 p., e35973

11.    The identification a novel, selective, non-steroidal, functional glucocorticoid receptor antagonist. Rimland, J., Dunne, A., Hunjan, S. S., Sasse, R., Uings, I., Montanari, D., Caivano, M., Shah, P., Standing, D., Gray, D., Brown, D., Cairns, W., Trump, R., Smith, P. W., Bertheleme, N., D'Alessandro, P., Gul, S., Vimal, M., Smith, D. N. & Watson, S. P. Apr-2010 In : Bioorganic & Medicinal Chemistry Letters. 20, 7, p. 2340-3, 4 p.

12.    Synthesis of 3-alkyl naphthalenes as novel estrogen receptor ligands. Fang, J., Akwabi-Ameyaw, A., Britton, J. E., Katamreddy, S. R., Navas III, F., Miller, A. B., Williams, S. P., Gray, D. W., Orband-Miller, L. A., Shearin, J. & Heyer, D. 15-Sep-2008 In : Bioorganic & Medicinal Chemistry Letters. 18, 18, p. 5075-5077, 3 p.

13.    Design and synthesis of an array of selective androgen receptor modulators. Trump, R. P., Blanc, J-B. E., Stewart, E. L., Brown, P. J., Caivano, M., Gray, D. W., Hoekstra, W. J., Willson, T. M., Han, B. & Turnbull, P. 2007 In : Journal of Combinatorial Chemistry. 9, 1, p. 107-14, 8 p.

14.    Pharmacological properties of the enhanced-affinity glucocorticoid fluticasone furoate in vitro and in an in vivo model of respiratory inflammatory disease. Salter, M., Biggadike, K., Matthews, J. L., West, M. R., Haase, M. V., Farrow, S. N., Uings, I. J. & Gray, D. W. 2007 In : American Journal of Physiology: Lung Cellular and Molecular Physiology. 293, 3, p. L660-7, 8 p.