Members of the Infectious Diseases Group

Dr Paul Denny, BSc (Hons), PhD

Contact Dr Paul Denny (email at p.w.denny@durham.ac.uk)

Biography

Protozoan parasites are the causative agents of a wide range of important human and animal diseases, including malaria. Current work in Paul's laboratory is focused on furthering the understanding of the role of lipid biosynthesis and membrane trafficking in host-pathogen interactions, with a view to elucidating protozoan specific activities amenable to therapeutic intervention. Previous to his appointment in 2004 Paul worked in research posts at Imperial College London and at the Medical Research Council's National Institute for Medical Research.

1. Mapping the apicomplexan sphingolipid biosynthetic pathway (with Dr Ehmke Pohl)

2. Targeting protozoan sphingolipid biosynthesis (with Dr Patrick Steel)

3. Antimicrobial peptides as antileishmanials (with Dr Steven Cobb)

Research Groups

School of Biological and Biomedical Sciences

• Biomolecular Interactions

Research Interests

• Cell Biology
• Lipid Biochemistry
• Molecular Biology
• Parasitology

Publications

Articles: magazine

• Denny.P.W. (2007). Turning up the heat on tropical disease. BBSRC Business 6.

Journal papers: academic

• Trmcic, M., Chadbourne, F.L., Brear, P.M., Denny, P.W., Cobb, S.L. & Hodgson, D.R.W. (2013). Aqueous synthesis of N,S,-dialkylthiophosphoramidates: design, optimisation and application to library construction and antileishmanial testing. Organic and Biomolecular Chemistry 11(16): 2660-2675.
• Pratt, S. , Wansadhipathi-Kannangara, N.K. , Bruce, C.R. , Mina, J.G., Shams-Eldin, H., Casas, J. Hanada, K., Schwarz, R.T. Sonda, S. & Denny, P.W. (2013). Sphingolipid synthesis and scavenging in the intracellular apicomplexan parasite, Toxoplasma gondii. Molecular and Biochemical Parasitology 187(1): 43-51.
• J.L. Norcliffe, E. Alvarez-Ruiz, J.J. Martin-Plaza, P.G. Steel & P.W. Denny (2013). The utility of yeast as a tool for cell-based, target-directed high-throughput screening. Parasitology
• Ali, H.Z., Harding, C.R. & Denny, P.W. (2012). Endocytosis and sphingolipid scavenging in Leishmania mexicana amastigotes. Biochemistry Research International 2012: 691363.
• Smith, TK, Reynolds, TB & Denny, PW (2012). Lipid Metabolism as a Therapeutic Target (Editorial). Biochemistry Research International 2012: 158139
• Young, S.A., Mina, J.G., Denny, P.W. & Smith, T.K. (2012). Sphingolipid and ceramide homeostasis, potential therapeutic targets. Biochemistry Research International 2012: 248135.
• Mina, J.G., Mosely, J.A., Ali, H.Z., Denny P.W. & Steel, P.G. (2011). Exploring Leishmania major inositol phosphorylceramide synthase (LmjIPCS): insights into the ceramide binding domain. Organic and Biomolecular Chemistry 9(6): 1823-1830.
• Featured in: Sheridan (2011). Industry continues dabbling with open innovation models. Nature Biotechnology 29(12): 1063.
• Chadbourne, F.L., Raleigh, C., Ali, H.Z., Denny, P.W. & Cobb, S.L. (2011). Studies on the antileishmanial properties of the antimicrobial peptides temporin A, B and 1Sa. Journal of Peptide Science 17(11): 751-755.
• Mina, J.G., Mosely, J.A., Ali, H.Z., Shams-Eldin, H., Schwarz, R.T., Steel, P.G. & Denny, P.W. (2010). A plate-based assay system for analyses and screening of the Leishmania major inositol phosphorylceramide synthase. International Journal of Biochemistry and Cell Biology 42(9): 1553-1561.
• Cobb, S.L. & Denny, P.W. (2010). Antimicrobial peptides for leishmaniasis. Current Opinion in Investigational Drugs 11(8): 868-875.
• Mina, J.G., Okada, Y. , Wansadhipathi-Kannangara, N.K., Pratt, S., Shams-Eldin, H., Schwarz, R.T., Steel, P.G., Fawcett, T. & Denny, P.W. (2010). Functional analyses of differentially expressed isoforms of the Arabidopsis inositol phosphorylceramide synthase. Plant Molecular Biology 73(4-5): 399-407.
• Mina, J.G., Pan, S.Y., Wansadhipathi, N.K., Bruce, C., Shams-Eldin, H., Schwarz, R.T., Steel, P.G. & Denny, P.W. (2009). The Trypanosoma brucei sphingolipid synthase, an essential enzyme and drug target. Molecular And Biochemical Parasitology 168(1): 16-23.
• Featured in: In Brief (2006). Research Highlights. Nature Reviews Drug Discovery 5(9): 722.
• Denny, P. W., Shams-Eldin, H., Price, H. P., Smith, D. F. & Schwarz, R. T. (2006). The protozoan inositol phosphorylceramide synthase: A novel drug target that defines a new class of sphingolipid synthase. Journal Of Biological Chemistry 281(38): 28200-28209.
• Morgan, GW, Denny, PW, Vaughan, S, Goulding, D, Jeffries, TR, Smith, DF, Gull, K & Field, MC (2005). An evolutionarily conserved coiled-coil protein implicated in polycystic kidney disease is involved in basal body duplication and flagellar biogenesis in Trypanosoma brucei. Molecular And Cellular Biology 25(9): 3774-3783.
• Stegmayer, C, Kehlenbach, A, Tournaviti, S, Wegehingel, S, Zehe, C, Denny, P, Smith, DF, Schwappach, B & Nickel, W (2005). Direct transport across the plasma membrane of mammalian cells of Leishmania HASPB as revealed by a CHO export mutant. Journal Of Cell Science 118(3): 517-527.
• Denny, PW, Morgan, GW, Field, MC & Smith, DF (2005). Leishmania major: clathrin and adaptin complexes of an intra-cellular parasite. Experimental Parasitology 109(1): 33-37.
• Denny, PW & Smith, DF (2004). Rafts and sphingolipid biosynthesis in the kinetoplastid parasitic protozoa. Molecular Microbiology 53(3): 725-733.
• Denny, PW, Goulding, D, Ferguson, MAJ & Smith, DF (2004). Sphingolipid-free Leishmania are defective in membrane trafficking, differentiation and infectivity. Molecular Microbiology 52(2): 313-327.
• Zufferey, R, Allen, S, Barron, T, Sullivan, DR, Denny, PW, Almeida, IC, Smith, DF, Turco, SJ, Ferguson, MAJ & Beverley, SM (2003). Ether phospholipids and glycosylinositolphospholipids are not required for amastigote virulence or for inhibition of macrophage activation by Leishmania major. Journal Of Biological Chemistry 278(45): 44708-44718.
• Denny, PW, Lewis, S, Tempero, JE, Goulding, D, Ivens, AC, Field, MC & Smith, DF (2002). Leishmania RAB7: characterisation of terminal endocytic stages in an intracellular parasite. Molecular And Biochemical Parasitology 123(2): 105-113.
• Morgan, GW, Hall, BS, Denny, PW, Field, MC & Carrington, M (2002). The endocytic apparatus of the kinetoplastida. Part II: machinery and components of the system. Trends In Parasitology 18(12): 540-546.
• Morgan, GW, Hall, BS, Denny, PW, Carrington, M & Field, MC (2002). The kinetoplastida endocytic apparatus. Part I: a dynamic system for nutrition and evasion of host defences. Trends In Parasitology 18(11): 491-496.
• Denny, PW, Field, MC & Smith, DF (2001). GPI-anchored proteins and glycoconjugates segregate into lipid rafts in Kinetoplastida. Febs Letters 491(1-2): 148-153.
• McKean, PG, Denny, PW, Knuepfer, E, Keen, JK & Smith, DF (2001). Phenotypic changes associated with deletion and overexpression of a stage-regulated gene family in Leishmania. Cellular Microbiology 3(8): 511-523.
• Williamson, DH, Denny, PW, Moore, PW, Sato, S, McCready, S & Wilson, RJM (2001). The in vivo conformation of the Plastid DNA of Toxoplasma gondii: Implications for replication. Journal Of Molecular Biology 306(2): 159-168.

Media Contacts

Available for media contact about:

• Infectious diseases: Parasites that affect both humans and animals

Grants Awarded

• 2014: Targeting the haemolytic phospholipase PlcHR from Pseudomonas aeruginosa as a novel drug target. British Society for Antimicrobial Chemotherapy (with Dr Ehmke Pohl)
• 2013: The plant IPCS as a novel herbicide target. BBSRC Industrial CASE award (with Prof Patrick Steel and Dr Stephen Lindell, Bayer Crop Science)
• 2012: Antifungals as novel antiprotozoals. N8 Research Partnership (with Prof Debbie Smith, York, and Aureogen Inc, USA)
• 2011: Kinetoplastid SLS inhibitors. MRC Industrial CASE award (with Dr Patrick Steel and Dr Andy Merritt, MRCT Ltd)
• 2011: Screening for antileishmanials. GSK Open Lab Award (Dr John Mina, with Dr Patrick Steel)
• 2011: Structure and Function of the P. aeruginosa PlcHR. Wellcome Trust Project Grant (with Dr Ehmke Pohl)
• 2011: Wellcome Trust Vacation Scholarship (Hannah Kerr, with Dr Patrick Steel)
• 2010: Probing the activity of the virulence factor PlcH from Pseudomonas aeruginosa. Guildford Bench Award (with Dr Ehmke Pohl)
• 2007: Academic Research Collaboration Award. British Council
• 2007: ORS Award (Nilu Wansadipathi)
• 2007: Wellcome Trust Vacation Scholarship (Clare Harding)
• 2006: ORS Award (John Mina, with Dr Patrick Steel)
• 2006: Toxoplasma: sphingolipids in host-parasite interactions, synthesis versus scavenging. BBSRC BB/D52396X/1
• 2005: Isolation of a protozoan sphingolipid synthase: a potential drug target. Royal Society 2005/R1

Supervises

• Miss Julie Thye
• Miss Frances Chadbourne
• Dr Morten Groftehauge
• Mr Christopher Brown
• Miss Jennifer Norcliffe