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Engineering genetic systems for control of Anopheles stephensi (Ref: 2019-21LA)


Project Description

A 3.5-year PhD studentship, fully funded by The Pirbright Institute and registered with the Royal Veterinary College of the University of London, is available to a highly motivated student interested in the genetic control of mosquitoes. The student will be mainly based at The Pirbright Institute but with regular visits to the University; a full range of research and transferrable skills training will be made available to the student as appropriate. The start date is anticipated to be January 2020.

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 control expression of Cas9, building on our prior experience of development of engineered sterile males, which have successfully entered field use. We take a synthetic biology approach, using rational design and standardised, characterised parts and modules to the extent possible, though recognising also than the degree of characterisation available is less than in some microbial systems. 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 the application process and application form can be found by visiting The Pirbright Institute’s website - click Visit Website. Please note that sending your CV attached to an email is not sufficient; your application will only be considered further if it is on the correct application form.
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.

Funding Notes

This studentship is open to science graduates (with, or who anticipate obtaining, at least a 2.1 or equivalent, in a relevant biological subject in their undergraduate degree, or a Master degree - subject to university regulations). Other first degrees, e.g. veterinary science, will be considered.
Students without English as a first language must provide evidence that they meet the English language requirement, e.g. with an IELTS score of 7.0 and no less than 6.5 in any of the subsections.
Eligible students will receive a minimum annual stipend of £15,009 and a small cost-of-living top-up; University registration fees will be paid.

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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