Manipulating sex determination pathways for pest control

CHAPMAN_U23DTP2

CRISPR/Cas9-based gene drives can introduce and spread genes and desirable traits into wild populations, offering a wide range of potential uses in insect pest control.

For example, they can spread sterility and reduce agricultural pest populations in a targeted and environmentally friendly way.

Gene drive technologies have often targeted highly basal elements of the sex determination pyramid to reduce the fitness of, or kill, females.

More efficient and controllable technologies can be designed to manipulate higher-level regulators of sexual fate to effect complete sex conversion (female to male).

These can potentially be deployed across a broad range of gene drive systems, to spread through a target population, causing a growing wave of sex ratio distortion, leading to rapid pest population reduction.

In this exciting project, the student will develop novel gene drives that utilise sex conversion as a population control measure by converting crop-damaging females into benign males. The model is a global agricultural pest, the medfly (Ceratitis capitata).

The student will gain cutting-edge research skills in molecular genetics, CRISPR/Cas9 technology, theoretical modelling and reproductive biology.

The project collaborates with the Pirbright Institute and Imperial College London, world-leading research centres for developing genetic technologies.

The project aims to manipulate sex determination pathways in the medfly to effect population control through gene editing, a gene drive system in which males are converted into XX pseudomales. The designs produced will then be evaluated in tests and theory.

The student will gain research skills in advanced genetic and genomic manipulations.

They will train at UEA, Pirbright and Imperial and gain key insights into developing and applying novel gene drive systems in the applied sector, as well as receiving excellent training and career development from the thriving Norwich Biosciences Doctoral Training Partnership.

References

Michelle Anderson, Estela Gonzalez, Matthew Edgington, Joshua Ang, Deepak-Kumar Purusothaman, Lewis Shackleford, Katherine Nevard, Sebald Verkuikl, Tim Harvey-Samuel, Philip T Leftwich, Kevin Esvelt, Luke Alphey. (2022) A multiplexed, confinable CRISPR/Cas9 gene drive propagates in caged Aedes aegypti populations. bioRxiv, https://doi.org/10.1101/2022.08.12.503466.

Alex Siddall, Tim Harvey-Samuel, Tracey Chapman, Philip T Leftwich. Manipulating insect sex determination pathways for genetic pest management: opportunities and challenges. (2022) Frontiers in Biotechnology and Bioengineering, 10: 867851.

Philip T Leftwich, Lewis G Spurgin, Tim Harvey-Samuel, Callum Thomas, Leonela Carabajal Paladino, Matthew P. Edgington, Luke S Alphey (2022). Genetic pest management and the background genetics of release strains. Philosophical Transactions of the Royal Society B. 376, 20190805.

Angela Meccariello, Marco Salvemini et al. (2019) Maleness-on-the-Y (MoY) orchestrates male sex determination in major agricultural fruit fly pests. Science doi: 10.1126/science.aax1 Philip T Leftwich, Michael Bolton, Tracey Chapman. (2016) Evolutionary biology and genetic techniques for insect control. Evolutionary Applications. 9, 212-230