This PhD opportunity is being offered as part of the LSTM and Lancaster University Doctoral Training Partnership. Find out more about the studentships and how to apply.
| Abstract | Insects are evolving resistance to insecticides, threatening global health and food security. A key driver of this resistance is that insects change how certain genes are switched on and off. These changes are largely controlled by transcription factors (the proteins that act as “switches” for genes). Many transcription factors rely on special reactive sites, which make them sensitive to chemical and environmental stress. This project will use chemical proteomics (specialised chemical probes that reveal which proteins interact with insecticides and how their reactive sites change) together with transcriptomics (sequencing to measure changes in gene activity) to uncover the key regulators of resistance. By linking changes at the RNA and protein level, the student will identify the most important “control points” and new genetic or protein markers of resistance. The project will provide training in quantitative analysis of large sequencing and proteomics datasets, alongside hands-on skills in chemical biology and molecular biology. The findings will help design better surveillance tools for resistance and may even suggest new ways to overcome it. |
| Where does this project lie in the translational pathway? | T1 - Basic Research |
| Methodological Aspects | Methodological aspects The project will combine laboratory work and computational approaches: 1. Chemical proteomics: Develop and apply chemical probes to identify proteins that interact with insecticides. 2. Transcriptomics: Use RNA sequencing to measure genome-wide changes in gene activity in resistant vs. susceptible insects. 3. Integration and analysis: Use statistical and machine-learning approaches to integrate protein- and RNA-level datasets, highlighting the most important transcription factors and regulators. 4. Validation: Laboratory testing to confirm the role of key regulators in resistance. |
| Expected Outputs | 1. Identification of transcription factors and reactive protein sites that control insecticide resistance. 2. A dataset linking gene activity, protein networks, and reactive amino acids to resistance outcomes. 3. New markers for tracking resistance in field populations. 4. At least two publications in peer-reviewed journals. 5. Transferable skills in big-data analysis, molecular biology, and interdisciplinary research. |
| Training Opportunities | 1. Technical training: chemical proteomics, sequencing, molecular biology. 2. Quantitative training: bioinformatics, statistics, integration of large datasets. 3. Professional development: presenting at international conferences, writing publications, and preparing funding applications. 4. Career preparation: skills directly relevant to careers in academia, biotech, pharma, and applied health research. |
| Skills Required | We welcome applicants from a wide range of scientific backgrounds. No prior expertise in entomology or resistance biology is required. The ideal student will have: 1. Enthusiasm for interdisciplinary science. 2. Interest in data analysis and problem-solving. 3. Willingness to learn both laboratory and computational techniques. 4. Students with background in chemistry and biochemistry are desirable but not essential 5. Experience with coding, statistics, or laboratory work would be helpful but is not essential. |
| Subject Areas | Malaria & other Vector Borne Diseases+ Resistance Research & Management |
| Key Publications associated with this project |
1. Balaska S, Grigoraki L, Lycett G, Weetman D, Oladepo F, Colman F, Vontas J, Paine MJI, Ismail HM. Predictive chemoproteomics and functional validation reveal Coeae6g-mediated insecticide cross-resistance in the malaria vector Anopheles gambiae. Provisionally accepted, Nature Communications (Pending final editorial revisions. This wi ll soon be available in LSTM archive) 2. Dyer NA, Lucas ER, Nagi SC, McDermott DP, Brenas JH, Miles A, et al. Mechanisms of transcriptional regulation in Anopheles gambiae revealed by allele-specific expression. Proceedings Biological sciences / The Royal Society. 2024;291(2031):20241142. https://doi.org/10.1098/rspb.2024.1142 3. Ingham VA, Wagstaff S, Ranson H. Transcriptomic meta-signatures identified in Anopheles gambiae populations reveal previously undetected insecticide resistance mechanisms. Nature communications. 2018;9(1):5282. https://doi.org/10.1038/s41467-018-07615-x 4. Ingham VA, Elg S, Nagi SC, Dondelinger F. Capturing the transcription factor interactome in response to sub-lethal insecticide exposure. Curr Res Insect Sci. 2021;1:None. doi: 10.1016/j.cris.2021.100018. 5. Ismail HM, O'Neill PM, Hong DW, Finn RD, Henderson CJ, Wright AT, et al. 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. 2013;110(49):19766-71. https://doi.org/10.1073/pnas.1320185110 |