How do insects that transmit tropical diseases metabolise and resist insecticides?

Insecticide resistance is the major threat to most insect borne diseases in the developing world, particularly mosquitoes that transmit malaria, dengue fever and zika.  This project will investigate precisely how insecticides are taken up by mosquitoes and metabolised in order to design new technology to fight tropical disease. 

Where does this project lie in the translational pathway?

T1; this  project is fundamental to understanding how insects are protected against chemical insult.   

Methodological aspects of the PhD project

Enzyme kinetics; in silico/ computational modelling; recombinant DNA and protein methods; proteomics; metabolomics;  analytical chemistry (e.g. HPLC, LC and GC MS/MS;);   microscopy; immunohistochemistry       

Expected outputs of the PhD project

1, Publications in specialist (biochemical, insect) and general journals e.g. JBC, Biochem J, PNAS, Curr Biol,  IBMB,

2. Pilot data for funding applications  e.g. BBSRC and Wellcome Trust

3. Development of new IP, tools and paradigms to counteract insecticide resistance 

What external industry links or training opportunities will be available for the student (ex. SMEs, industry, health agencies)?

SME Placement:  Innovative Physical Organic Solutions (IPOS), Huddersfield University will co-supervise and provide training in analytical chemistry and metabolomics

 

Required skills/experience/aptitudes

Degree in biological or chemical discipline.

Key publications that relate to this proposed project

1.

Yunta, C., Grisales, N., Nász, S., Hemmings, K., Pignatelli, P., Voice, M., Ranson, H., Paine, M.J.I., (2016) Pyriproxyfen is metabolized by P450s associated with pyrethroid resistance in An. gambiae. Insect Biochem. Mol. Biol. 78, 50–57. doi:10.1016/j.ibmb.2016.09.001

2.

Ismail, H., O’Neill, P., Hong, D.,  Finn, R.D., Henderson, C.J. Wright, A. T., Cravatt, B. F., Hemingway, J., and Paine, M. J. I. (2013) Pyrethroid Activity-Based Probes for Profiling Cytochrome P450 Activities Associated with Insecticide Interactions Proc National Acad Sci. USA. Nov 18th early edition. doi 10.1073/pnas.1320185110

3.

Edi, C. V., Djogbenou, L., Jenkins, A. M., Regna, K., Muskavitch, M. A., Poupardin, R., Jones, C. M., Essandoh, J., Ketoh, G. K., Paine, M. J., Koudou, B. G., Donnelly, M. J., Ranson, H., and Weetman, D. (2014) CYP6 P450 Enzymes and ACE-1 Duplication Produce Extreme and Multiple Insecticide Resistance in the Malaria Mosquito Anopheles gambiae. PLoS genetics 10, e1004236

4.

Bradley J. Stevenson , Jaclyn Bibby , Patricia Pignatelli , Sant Muangnoicharoen , Paul M. O’Neill , Lu-Yun Lian , Pie Müller, Dimitra Nikou , Andrew Steven , Janet Hemingway , Michael J. Sutcliffe , Mark J. I. Paine  (2011) Cytochrome P450 6M2 from the malaria vector Anopheles gambiae metabolizes pyrethroids: sequential metabolism of deltamethrin revealed.  Insect Biochem Mol Biol.  41 492 – 50

5.

David J.P, Ismail H.M, Chandor-Proust A, Paine M.J.I (2013) Role of cytochrome P450s in insecticide resistance: impact on the control of mosquito-borne diseases and use of insecticides on Earth. Philos Trans R Soc Lond B Biol Sci 368: 20120429. (Top 10 most cited in 2013)

The deadline for applications is Friday 20th July 2018 23.45 BST.

More information on this programme can be found here

here

https://www.ka4alka.com.ua

http://medicaments-24.net