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Identification of the molecular mechanisms of longevity in long-lived mutants of insulin and Klotho signalling


Project Description

Aim and hypothesis

The aim of this project is to understand at molecular level the cellular changes that are
regulated by insulin signalling and Klotho in longevity. Specifically we will identify the FOXO/DAF-16 target genes up- or down regulated in long-lived C. elegans mutants.

Methodology and innovations

a) To identify the downstream targets of FOXO/DAF-16, our existing long-lived C. elegans mutant strains will be used (either alone or in various combinations) and quantitative PCR (qPCR) of candidate target genes and/or transcriptome analysis using microarrays will be carried out. The datasets will be referenced to wild type C. elegans.
b) To validate any identified hits in (a), genetic mutants (where available, or RNAi/targeted mutagenesis of the identified hits) will be used in combination with classical genetic methods (e.g. epistasis analysis) to assess how mutations in the identified hits alter longevity of the long-lived worms

Funding Notes

DTA3/COFUND participants will be employed for 36 months with a minimum salary of (approximately) £20,989 per annum. Tuition fees will waived for DTA3/COFUND participants who will also be able to access an annual DTA elective bursary to enable attendance at DTA training events and interact with colleagues across the Doctoral Training Alliance(s).
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 801604.

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