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Local gene drives for mosquitoes


Project Description

A PhD studentship funded by The Pirbright Institute is available to highly motivated students interested in genetic control of mosquitoes.

New tools are required for improved malaria control or elimination. The development of CRISPR-based systems has led to a resurgence of interest in “gene drive” methods. Gene drives bias inheritance in their favour and can thereby, in principle, persist and even increase in allele frequency in wild populations despite not conferring an individual fitness benefit. However, simple CRISPR/Cas9-based designs may spread through entire species, which is unlikely to be desirable in all cases. Instead, we seek to develop alternative gene drive designs allowing intervention in one population with minimal impact on nearby non-target populations of the same species. The student will focus on the development of such population-level drive systems in the mosquito Anopheles stephensi, an important malaria vector that is also relatively amenable to genetic studies.

The ‘daisy drive’ concept provides an elegant conceptual method for limiting both spatial spread and temporal persistence of CRISPR/Cas designs. The daisy drive is a multi-component ‘split drive’ system, in which each element drives (‘homes’) only in the presence of the previous element in the chain. However, the first element of the chain does not drive, so forming a ‘licensing factor’ or ‘tether’ for the whole system, limiting its geographic spread.

Key to homing drives is controlling the ‘homing’. It is crucial for many designs that this occurs only where intended, which is premeiotic germline cells, and not elsewhere, e.g. embryos via maternal deposition, somatic cells, etc. Expression elsewhere can have severely negative consequences on fitness, resistance and other aspects of drive performance.

The student will develop methods to restrict expression of Cas9 to the germline. We take a synthetic biology approach, using rational design and standardised, characterised parts and modules to the extent possible, however germline restriction can only be verified by generating transgenic insects. The Pirbright Arthropod Genetics Group has several related gene drive and genetic control projects ongoing, with about 24 research staff; world-leading expertise and resources are available.

TO APPLY: Full details of how to apply can be found on our website - click Visit Website.
For enquiries regarding the application process please email Admissions Enquiries - click Email Now.
For informal enquiries regarding this project please email the project supervisors noted above.
Please note: Due to the current COVID-19 situation there is likely to be a delay with recruitment/possible delay to the start date of this studentship.

Funding Notes

This is a fully funded studentship open to science graduates with, or who anticipate obtaining, at least 2.1 or equivalent in a relevant biological subject in their undergraduate degree, or a Masters degree - subject to university regulations. Other first degrees, eg medical or veterinary science, will be considered. Open to UK, EU and international students. Eligible students will receive minimum annual stipend of £15,285 plus cost of living top-up of £2,200; university registration fees will be paid. Students without English as first language must provide evidence of IELTS score of 7.0 and no less than 6.5 in any subsections.

References

- Alphey, L. (2014). "Genetic Control of Mosquitoes." Annual Review of Entomology 59: 205-224
- Noble, C., et al. (2019). "Daisy-chain gene drives for the alteration of local populations." Proceedings of the National Academy of Science (USA) 116: 8275-8282.

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