New malaria control interventions though targeting the mosquito blood meal; determining the endectocidal and gametocytocidal effects of novel chemotherapeutics.

A number of drugs administered to humans to control malaria and other infectious diseases have been observed to have an additional benefits by reducing onward malaria transmission. For example the drug ivermectin, a broad-spectrum antiparasitic compound used for the treatment and control of onchocerciasis and lymphatic filariasis has also be observed to kill malaria mosquitoes who feed on treated individuals (endectocidal). 

Similarly the anti-malarial drug primaquine kills Plasmodium falciparum gametocytes, the sexual stage of the parasite found in the mosquito vector, thereby preventing transmission (gametocytocidal). The aim of this project is to determine the endectocidal and gametocytocidal impacts of a range of chemotherapeutics administered individually and in combinations. The candidate will be based between the departments of Vector Biology and Tropical Disease Biology and will conduct a range of experiments including experimental mosquito infections both in the UK and sub Saharan Africa.  The study will involve a number of technologies, including; molecular genetic screening, high-content imaging, confocal laser scanning microscopy, flow cytometry/cell sorting and potentially analytical techniques e.g. LC-MS/MS.

Where does the project lie on the Translational Pathway?

T1 (Basic Research) + T2 (Human/Clinical Research) + T3 (Evidence into Practice)

Expected Outputs

The project will produce high quality REF returnable 3*/4* publications and will provide the evidence base for large scale research council and industry funding. Recent PhD graduates from our labs have published extensively in the general science journals (Nature, PNAS, Nature Communications). This is a key strategic area for LSTM and brings together research groups from across the Biological Sciences faculty

Training Opportunities

The student will gain skills in rigorous, replicated experimental design; statistical analysis; mosquito rearing; experimental infections; parasitology;  molecular genetic screening, high-content imaging, confocal laser scanning microscopy, flow cytometry/cell sorting and potentially analytical techniques e.g. LC-MS/MS. Microscopy.  Quantitative skills involve statistical analyses and potentially some PK-PD modelling.

 

Skills Required

 

Key Publications associated with this project

Smit, M.R. et al 2018 Safety and mosquitocidal efficacy of high-dose ivermectin when co-administered with dihydroartemisinin-piperaquine in Kenyan adults with uncomplicated malaria (IVERMAL): a randomised, double-blind, placebo-controlled trial. Lancet Infectious Diseases, 18,  ‏ 615-639 

Graves, P.M. et al 2018 Primaquine or other 8‐aminoquinolines for reducing Plasmodium falciparum transmission. Cochrane Systematic Review - Intervention Version published: 02 February 2018 https://doi.org/10.1002/14651858.CD008152.pub5

Staedke, S.G. et al 2020Effect of long-lasting insecticidal nets with and without piperonyl butoxide on malaria indicators in Uganda (LLINEUP): a pragmatic, cluster-randomised trial embedded in a national LLIN distribution campaign. Lancet, 395, 1292-1303

Camarda, G et al 2019  Antimalarial activity of primaquine operates via a two-step biochemical relay. Nature Communications, 10, e3226

McPhillie, M.J. et al 2020 Potent Tetrahydroquinolone Eliminates Apicomplexan Parasites. Frontiers in Cellular and Infection Microbiology, 10, e203

Deadline: Thursday 11th February 2021; 12:00 noon GMT

Further details on the MRC/DTP and CASE programmes and application guidance and process can be found here