REF. NO. 2014_02 JK/LA/GL Liverpool Click here to apply TITLE

REF. NO. 2014_02 JK/LA/GL Liverpool
Click here to apply
TITLE: Molecular components of sexual development in Aedes aegypti and Aedes albopictus
ANTICIPATED START DATE: January 2015
DURATION: 4 years full-time
ELIGIBILITY:
 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 Masters degree (subject to university regulations).
Other first degrees, e.g. veterinary science, will be considered. You should be looking for a challenging,
interdisciplinary research training environment and have an active interest in the control of infectious diseases.
 This is fully-funded studentship only open to UK students and eligible EU students who qualify for home-rated fees, in
line with BBSRC criteria http://www.bbsrc.ac.uk/web/FILES/Guidelines/studentship_eligibility.pdf.
 Students without English as a first language must also 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.
SUPERVISION:
Principal Supervisor:
Co-Supervisor:
University Supervisor:
Dr Jaroslaw Krzywinski (Pirbright)
Professor Luke Alphey (Pirbright)
Dr Gareth Lycett (Liverpool School of Tropical Medicine/University of Liverpool)
PROJECT DETAILS
Mosquito-borne viral diseases affecting livestock and man constitute a major international problem. Periodic epidemic
outbreaks of Rift Valley fever, chikungunya, Japanese encephalitis, or dengue have devastating consequences to local
economies, primarily in the poor tropical countries. An outbreak of chikungunya in Italy and a rapid spread of its vector,
Aedes albopictus, in Europe show that the danger is also looming in more temperate regions. Management of arboviral
diseases relies heavily, or solely on the use of insecticides to control mosquito vectors. However, their effectiveness is
threatened by the emergence of insecticide resistance. Alternative mosquito control methods are, thus, urgently
needed. One of the proposed methods is the sterile insect technique (SIT). It relies on repeated massive releases of
sterile males, whose mating with native females produces no offspring, leading to a crash of target populations. SIT
has proved spectacularly successful in elimination of serious agricultural pests, but its use for mosquito control is
hampered by lack of adequate methods of sorting males from females.
Technological advances have opened prospects for the development of transgenic Aedes strains that would produce
conditional male-only generations suitable for SIT. Such approaches depend on the identification of sex- specific genes
that could serve as targets to induce female lethality or masculinisation (sex reversal to phenotypic males). Elimination
of females at the embryonic stage would drastically reduce costs of male production for releases. Therefore, the sex
determination pathway is expected to provide optimal targets.
In insects sex is determined in early embryos by a primary signal that triggers a life-long expression of a cascade of sexspecifically spliced genes (in Drosophila: sxl > tra/tra2 > dsx), whose products control all developmental processes.
Elements of the cascade have been identified only in several non-drosophilid species. Comparisons of their sequences
revealed an astonishing variety of primary signal genes and (apart from the well conserved dsx) high evolutionary
lability of other subordinate genes. Importantly, in all studied species, knockdown of genes located upstream of dsx led
to female masculinization or death at the embryo stage.
In mosquitoes only dsx has been described. Therefore, the project aims to identify other sex determination genes and
dissect their function in two major arbovirus vectors, Aedes aegypti and A. albopictus, using comparative genomics
tools and state-of-the-art methods of male and female transcriptome profiling, gene functional analysis, and insect
transgenesis. The specific objectives of the project are:
1. Identify Aedes orthologs of candidate sex determination genes detected recently by our group in
Anopheles gambiae.
2. Conduct an RNA-seq-based analysis of transcriptomes of the A. aegypti male and female neonate first
instar larvae to identify sex-specific transcripts indicative of sex-determining function.
3. Experimentally validate sex-specificity of transcription from all candidate sex determination genes and
conduct their functional characterization using transient assays.
4. For all genes validated in A. aegypti, identify orthologs in A. albopictus and conduct their functional
analysis.
5. Generate proof-of-concept transgenic strains of A. aegypti with conditional female-lethal or sexreversal phenotype.
FUNDING:
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This is a BBSRC fully funded project. The student will be based at the Pirbright Institute and registered with the
University of Liverpool.
Eligible students will receive a minimum annual stipend of £13,863 plus cost of living top-up. University
registration fees will be paid, and funding for consumables and travel will be provided.
All students at The Pirbright Institute are offered free membership of the SGM for the duration of their studies.
Further information regarding the partner institutions can be found at:
www.pirbright.ac.uk/
http://www.liv.ac.uk/
http://www.lstmliverpool.ac.uk

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