Dr Mark Paine

Reader

Dr Paine graduated in Genetics from Wits University, Johannesburg in 1983. In 1990 he obtained his PhD for research on the molecular biology of viper venoms from the Liverpool School of Tropical Medicine. In 1993 he moved to the University of Dundee Biomedical Research Centre to work on molecular aspects of human drug metabolising enzymes.  In 2006 he swopped man for mosquitoes and returned to the Liverpool School of Tropical Medicine to work on the related chemical detoxification mechanisms of insects, and the problem of insecticide resistance.

Teaching

Aspects of vector biology, insecticide resistance and vector control for undergraduate and postgraduate modules.

Research

Spraying

Enzyme Characterisation Group (ECG)

Research in the ECG  is aimed principally at understanding the molecular mechanisms of insecticide resistance and to translate this knowledge into practical solutions for tropical diseases.  Our basic aim is to identify the proteins and the processes leading to resistance. This involves the use of a broad range of biochemical and molecular techniques and collaborations with transgenic, structural and computational modeling groups.  Over the past five years, through IVCC funding (www.IVCC.com) we have made substantial progress in identifying the major P450’s associated with pyrethroid resistance in Anopheline and Culicine vectors of malaria and dengue (reviewed in David et al, 2013 http://rstb.royalsocietypublishing.org/content/368/1612.toc). Allied to this are studies on heme oxygenase, which is involved in heme detoxification, thus crucial to the survival of blood-sucking insects.  Funded by the Leverhulme Trust, we are asking the question, how do mosquitoes survive a blood meal? – see August 2012 Leverhulme Newsletter http://www.leverhulme.ac.uk/news/newsletter.cfm.  We also have a major interest in the development of novel biosensors for the detection and monitoring of insecticides. We recently secured funding from the Wellcome Trust Affordable Healthcare in India Scheme to develop simple visual assays (quantification tests) for the rapid and reliable monitoring of DDT, carbamate and organophosphates. These will be used in Visceral Leishmaniasis and malaria control operations in India and worldwide . (http://www.wellcome.ac.uk/Funding/Technology-transfer/Funded-projects/India/index.htm).  Finally, we work with diverse academic, industry and government organisations and are open to new collaborations and contract research opportunities.

Students

  • Selcan Alptekin, Investigating the interaction of the methylene dioxyphenyl moiety with resistance associated  P450s  (Syngenta/HGCA)  (1/10/2010)
  • Cherry Dyke, Mechanisms of insecticide resistance in  An. stephensi (NIH-Fogarty International Center) (1/05/2012)
  • Mark Mallot, A genomic approach to understanding insecticide resistance in diamondback moth (Plutella xylostella) (BBSRC/Syngenta) (01/10/12)
  • Christopher Spencer, Molecular characterisation of An. gambiae heme oxygenase (Leverhulme) (01/10/12)
  • Glauber Pacelli, Biochemical, structural and physiological characterization of Aedes aegypti heme oxygenase: a novel target for dengue control (CNPq)  (01/04/13)

Staff

  • Dr Marlize Coleman, Project Manager, Insecticide Quantification Kits (IQK) for Vector Control Programmes in India’
  • Dr Hanafy Ismail,  Post Doctoral Research Assistant, IQK development
  • Dr Cristina  Yunta-Yanes, Post Doctoral Research Asistant,  Structure/ function of P450s associated with insecticide resistance
  • Ms Kay Hemmings, Technician/ ECG lab manager,  Enzyme characterisation
  • Mr Christopher Williams, Technician, Immunodiagnostics 

Current Projects

  • 2013 to 2015

    Improving the impact of IRS for Visceral Leishmaniasis with enabling integrated decision support systems

    $2,233,443 - (PI Hemingway, Co-Pi, Paine, Coleman and Coleman)

    Donors: Bill and Melinda Gates Foundation
  • 2013 to 2016

    Affordable Healthare in India Translation Award. Insecticide Quantification Kits (IQK) for Vector Control Programmes in India

    £955,627 - (PI Paine)

    Donors: Wellcome Trust
  • 2014 to 2017

    Defining the mechanism of action of the 8-aminoquinolines: A pre-requisite to rationally designed safe antimalarials for the elimination era

    £518,135 - Biagini GA (PI), O’Neill PM, Paine M, Ward SA and Baker D (Co-Is)

    Donors: Medical Research Council
  • 2012 to 2015

    Molecular Characterisation of Anopheles gambiae Heme Oxygenas

    £205,361 - (PI Paine, Co-Pi, Lycett and Lian)

    Donors: Leverhulme Trust
  • 2011 to 2015

    African Vector Control: New tools. (PI Ranson LSTM; 33% of Euro 1 m for Work Package

    €330,000 - (Co-PIs G. Lycett, M Paine and P. McCall)

    Donors: EU AVECNET
  • 2012 to 2016

    National Institutes of Health/ National Institute for Allergies and Infectious Diseases. Program for Resistance, Immunology, Surveillance and Modelling of Malaria in Uganda (PRISM)

    $309,284 - (PI Dorsey UCSF Collaborator M Paine)

  • 2014

    Quantification of pyripoxyfen and permethrin from ITNs

    £13,078 - (Pi, Paine)

    Donors: IVCC
  • 2014

    IVCC, in vitro characterisation of insecticide metabolism of P450s

    £5,980 - (Pi, Paine)

Publications

  • Selected Publications

    Morou E.,  Dowd A.J., Rajatileka S., Steven A., Hemingway J., Ranson H., Paine M.* and Vontas J.(2010) A simple colorimetric assay for specific detection of glutathione-S transferase activity associated with DDT resistance in mosquitoes. PLoS NTD.  In press

    Matambo, T.S., Paine, M.J.I., Coetzee, M., and Koekemoer, L.L. (2010) Sequence characterisation of cytochrome P450 CYP6P9 in pyrethroid resistant and susceptible Anopheles funestus (Dipera: Culicidae). Gen Mol Res.  9, 554-564

    Karunker I, Morou E, Nikou D, Nauen R, Sertchook R, Stevenson BJ, Paine MJ, Morin S, Vontas J (2009) Structural model and functional characterization of the Bemisia tabaci CYP6CM1vQ, a cytochrome P450 associated with high levels of imidacloprid resistance. Insect Biochem Mol Biol39, 697-706

    Dowd A.J., Morou, E., Steven, A., Ismail, H.M., Labrou. N. Hemingway, J.,  Paine, M.J.I* and Vontas, J. (2010) Development of a colorimetric pH assay for the quantification of pyrethroids based on Glutathione-S-Transferase Int. J. Env. Anal. Chem. In press

    Dowd, A.J., Steven , A, Morou, E.A., Hemingway, J, Vontas, J. and  Paine, M.J.I. (2009)  A simple glutathione transferase -based colorimetric endpoint assay for insecticide detection. Enz and Micro Tech. 45, 164-168

    Müller, P., Warr, E., Stevenson, B. J., Pignatelli, P., Morgan, J., Steven, A., Yawson, A. E., Mitchell, S., Hemingway, J., Ranson, H., Paine, M., and Donnelly, M. J. (2008) Field-caught permethrin-resistantAnopheles gambiae s.s. overexpress CYP6P3, a P450 that metabolizes pyrethroids. PLoS Genetics4, e1000286

    Kapelyukh, Y., Paine, M.J.I.*  Maréchal, J-D,  Sutcliffe, M.J., Wolf, C.R. and Roberts, G.C.K. (2008)  Multiple substrate binding by cytochrome P450 3A4: estimation of the number of bound substrate molecules.  Drug Met. Disp36, 21636-44

    Axarli I, A, Kapoli P A, Platis D., Fragulaki, M, Paine, M J I, Hemingway, J., Vontas, J. and Labrou, N. E.  (2008) Engineering sensitive glutathione transferase for the detection of xenobiotics. Biosensors and Bioelectronics24,498-504.

    McLaughlin L.A, Niazi U, Bibby J, David J-P, Vontas J, Hemingway J, Ranson H, Sutcliffe M. J, Paine M.J.I. (2008) Characterization of inhibitors and substrates of Anopheles gambiae CYP6Z2. Insect Mol Biol17, 125-35.

    Morou E, Ismail HM, Dowd AJ, Hemingway J, Labrou N, Paine M,* Vontas J. (2008) A dehydrochlorinase-based pH change assay for determination of DDT in sprayed surfaces. Anal Biochem378, 60-4.

    Marechal J-D, Kemp C.A., Roberts , G.C.K, Paine M.J.I, Wolf, C.R. and Sutcliffe M.J. (2008)  Insights into drug metabolism by cytochromes P450 from modelling studies of CYP2D6-drug interactions. British Journal of Pharmacology 153, S82-S89