Staff Profile: Mark Paine, BSc., PhD
Areas of interest: Molecular understanding of detoxification mechanisms in insect vectors and development of new reagents to overcome insecticide resistance.
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.
Aspects of vector biology, insecticide resistance and vector control for undergraduate and postgraduate modules.
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.
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)
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 and grants
$2,233,443 - Bill and Melinda Gates Foundation, Improving the impact of IRS for Visceral Leishmaniasis with enabling integrated decision support systems. 01/12/13 – 31/01/15 (PI Hemingway, Co-Pi, Paine, Coleman and Coleman))
£955,627 - Wellcome Trust, Affordable Healthare in India Translation Award. Insecticide Quantification Kits (IQK) for Vector Control Programmes in India’ 1/02/13 – 1/08/16 (PI Paine)
£518,135 - Medical Research Council- “Defining the mechanism of action of the 8-aminoquinolines: A pre-requisite to rationally designed safe antimalarials for the elimination era” Biagini GA (PI), O’Neill PM, Paine M, Ward SA and Baker D (Co-Is) 2014-2017
£205,361 - Leverhulme Trust, Molecular Characterisation of Anopheles gambiae Heme Oxygenas (PI Paine, Co-Pi, Lycett and Lian). 1/10/2012 – 30/09/15
€330,000 - EU AVECNET African Vector Control: New tools. (PI Ranson LSTM; 33% of Euro 1 m for Work Package - Co-PIs G. Lycett, M Paine and P. McCall). 1/7/11 – 30/6/15
$309,284 - National Institutes of Health/ National Institute for Allergies and Infectious Diseases. Program for Resistance, Immunology, Surveillance and Modelling of Malaria in Uganda (PRISM) (PI Dorsey UCSF Collaborator M Paine) 2012 – 2016
£13,078 - IVCC, Quantification of pyripoxyfen and permethrin from ITNs, 01/03/14 – 31/12/14 (Pi, Paine)
£5,980 - IVCC, in vitro characterisation of insecticide metabolism of P450s, 01/03/14 – 31/12/14 (Pi, Paine)
Russell, Tanya L., Morgan, John, Ismail, Hanafy, Kaur, Harparkash, Eggelte, Teunis, Oladepo, Folasade, Amon, James, Hemingway, Janet, Iata, Harry and Paine, Mark (2014) 'Evaluating the feasibility of using insecticide quantification kits (IQK) for estimating cyanopyrethroid levels for indoor residual spraying in Vanuatu'. Malaria Journal, Vol 13, Issue 1, e178.
Mitchell, Sara N., Rigden, Daniel J., Dowd, Andrew J., Lu, Fang, Wilding, Craig S., Weetman, David, Dadzie, Samuel, Jenkins, Adam M., Regna, Kimberly, Boko, Pelagie, Djogbenou, Luc, Muskavitch, Marc A. T., Ranson, Hilary, Paine, Mark, Mayans, Olga and Donnelly, Martin (2014) 'Metabolic and Target-Site Mechanisms Combine to Confer Strong DDT Resistance in Anopheles gambiae'. PLoS ONE, Vol 9, Issue 3, e92662.
Edi, Constant V.A., Djogbenou, Luc, Jenkins, Adam M., Regna, Kimberly, Muskavitch, Marc A. T., Poupardin, Rodolphe, Jones, Christopher M., Essandoh, John, Kétoh, Guillaume K., Paine, Mark, Koudou, Benjamin, Donnelly, Martin, Ranson, Hilary and Weetman, David (2014) 'CYP6 P450 Enzymes and ACE-1 Duplication Produce Extreme and Multiple Insecticide Resistance in the Malaria Mosquito Anopheles gambiae'. PLoS Genetics, Vol 10, Issue 3, e1004236.
Riga, M., Tsakireli, D., Ilias, A., Morou, E., Myridakis, A., Stephanou, E.G., Nauen, R., Dermauw, W., Van Leeuwen, T., Paine, Mark and Vontas, John (2014) 'Abamectin is metabolized by CYP392A16, a cytochrome P450 associated with high levels of acaricide resistance in Tetranychus urticae'. Insect Biochemistry and Molecular Biology, Vol 46, pp. 43-53.
Ismail, Hanafy, O'Neill, Paul M, Hong, David W, Finn, Robert D, Henderson, Colin J, Wright, Aaron T, Cravatt, Benjamin F, Hemingway, Janet and Paine, Mark (2013) 'Pyrethroid activity-based probes for profiling cytochrome P450 activities associated with insecticide interactions.'. Proceedings of the National Academy of Sciences of the United States of America, Vol 110, Issue 49, pp. 19766-19771.
- 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 Biol. 39, 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-resistant Anopheles gambiae s.s. overexpress CYP6P3, a P450 that metabolizes pyrethroids. PLoS Genetics. 4, 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. Disp. 36, 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 Bioelectronics. 24,498-504.
- 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 Biol. 17, 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 Biochem. 378, 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