Description du poste
Insect populations are declining worldwide, and agrochemical pollution is a principal driver. Current insecticide safety assessments underestimate environmental harm because they rely mainly on short-term mortality tests on a few surrogate species, most often honeybees, and overlook sublethal and community-level effects. The central environmental problem this project will solve is evolutionary: broad-spectrum insecticides—pyrethroids, neonicotinoids, organophosphates, carbamates and diamides—act on molecular targets conserved across the arthropod phylogeny, so pests, pollinators, natural predators and parasitoids share vulnerability through ‘toxicity by descent’. This project will deliver a predictive, evolution-informed molecular docking framework that protects beneficial insects by quantifying how sequence and structural divergence in insecticide target proteins translates into differential susceptibility across species. Key research questions are: (1) How does target-site divergence across arthropod phylogenies predict insecticide binding and toxicity? (2) Can molecular docking of representative insecticides against structurally modelled target proteins recapitulate documented resistance and species-sensitivity data? (3) Can the resulting framework guide selection of chemistries that spare vulnerable nontarget species and reduce environmental pollution? To answer these questions, the project will compile target-protein sequences for five major insecticide classes across a phylogenetically representative panel of pests and beneficial arthropods, generate and refine structural models using homology modelling and AlphaFold, and run validated molecular docking pipelines against a panel of environmentally relevant insecticides. Predictions will be benchmarked against empirical resistance and sensitivity data from the literature and validated experimentally in Drosophila melanogaster and cell-based assays. The outcomes are oriented directly to solving an environmental problem: a species-risk prioritisation framework and a cheminformatics tool that enable regulators and industry to identify at-risk species, avoid harmful chemistries and design safer insecticides, informing evidence-based risk assessment under the precautionary principle and contributing to halting insect declines. The project will run over 3.5 years: Year 1 will focus on phylogenomic data assembly and structural modelling; Year 2 on docking pipeline development and benchmarking; Year 3 on experimental validation and case-study application with the industrial partner; the final six months on integration, thesis writing and dissemination. For further information on this project and details of how to apply to it please click the 'Apply' button above. Further information on how to apply for a CENTA studentship can be found on the CENTA website: https://centa.ac.uk/apply/ Funding notes: This project is offered through the CENTA3 DLA, funded by the Natural Environment Research Council (NERC). Funding covers: annual stipend, tuition fees (at home-fee level), Research Training Support Grant. Academic requirements: at least a 2:1 at UK BSc level or a pass at UK MSc level or equivalent. Further information: https://centa.ac.uk/apply/ International students are eligible for studentships to a maximum of 30% of the cohort. Funding does not cover any additional costs relating to moving or residing in the UK. International applicants must fulfil the international student entry requirements, including English language: https://www.birmingham.ac.uk/postgraduate/pgt/requirements-pgt/international/index.aspx . References: Colbourne et al. 2022. Toxicity by descent: A comparative approach for chemical hazard assessment. Environmental Advances 9: 100287. Gandara et al. 2024. Pervasive sublethal effects of agrochemicals on insects at environmentally relevant concentrations. Science 386. LaLone et al. 2023. From protein sequence to structure: The next frontier in cross-species extrapolation for chemical safety evaluations. Environmental Toxicology and Chemistry 42. Weston et al 2013. Multiple origins of pyrethroid insecticide resistance across the species complex of a nontarget aquatic crustacean, Hyalella azteca. Proceedings of the National Academy of Sciences 110.