PhD Studentship: CENTA 2027-B06 Combatting Insecticide Pollution: An Evolution-Informed Molecular Docking Framework to Protect Pollinators and Beneficial Insects

University of Birmingham; Birmingham; On-site; GBP 18,000 - 20,000; Full time

Job summary

University of Birmingham invites applications for a PhD project addressing global insect declines by developing an evolution-informed molecular docking framework. The role will assemble target-protein sequences across arthropods, generate structural models with AlphaFold and homology modelling, and benchmark docking against resistance data.

The aim is a species-risk prioritisation framework and safer chemistries to guide regulators and industry toward reduced environmental pollution, with a

Job description

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.

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.