Project highlights

  • Why individuals and species age so differently is an unanswered question in evolutionary biology.
  • Diapause is an example of senescence plasticity, where the same genetics produces different ageing patterns in an organism
  • Using next-gen sequencing the project will measure DNA methylation across the genome of Nasonia and build the first insect epigenetic clock.

Overview

Why individuals and species age so differently is an unanswered question in evolutionary biology. Ageing is the combination of DNA, cellular and organ damage leading to a decline in function and increased chance of dying. This project will combine two major themes in the study of ageing; epigenetic clocks and senescence plasticity.

An epigenetic clock is an emergent property of the epigenome which is a better measure of true biological age than chronological age. Epigenetic clocks are used widely through-out biogerontology. Epigenetic clocks are calculated by combining chronological age and epigenetic marks (methylation) on genes to give a better representation of biological age.

Diapause is an overwintering stage in some insects where development is arrested. There are many differences between diapaused insects and non-diapaused members of the same species, including a decrease in ageing during and after diapause. Diapause is an example of senescence plasticity, where the same genetics produces different ageing patterns in an organism.

Nasonia (a small hymenopteran) exposed to short photoperiod and 20 degrees C initially produce offspring which do not go through diapause but then switch to producing diapause bound offspring by day eight of laying. When they are seven days old, the nondiapaused larvae will begin to pupate and continue their normal development. The diapaused offspring remain suspended as larvae for up to eighteen months. DNA methylation is involved in Nasonia diapause.

Using next-gen sequencing the project will measure DNA methylation across the genome of Nasonia. We will then build the first insect epigenetic clock. We can then compare ageing in diapaused/normal larvae and diapaused/normal adults to see does diapause affect this epigenetic ageing.

This project, by developing an insect model of epigenetic ageing, is ambitious, adventurous and beyond the state-of-the- art. Current invertebrate models of ageing (Drosophila and C. elegans) do not possess DNA methylation, reducing their generality. Future study into diapause as an example of senescense plasticity could allow us to differentiate between various similar theories for the evolution of ageing. If adult ageing is affected by early life experiences this could have wide consequences for understanding life history traits in insects.

Host

University of Leicester

Theme

  • Organisms and Ecosystems

Supervisors

Project investigator

Prof. Eamonn Mallon, University of Leicester ([email protected])

Co-investigators

Prof. Bambos Kyriacou, University of Leicester ([email protected])

How to apply

Methodology

This project combines whole genome bisulfite sequencing of age controlled larval and adult Na- sonia vitripennis and penalised regression analysis to analyse epigenetic ageing in diapaused and non-diapaused Nasonia.

Training and skills

Students will be awarded CENTA2 Training Credits (CTCs) for participation in CENTA2-provided and ‘free choice’ external training. One CTC equates to 1⁄2 day session and students must accrue 100 CTCs across the three years of their PhD.

The student will be provided with training, as required, in R, a powerful and increasing popular statistical programming language, Python, a general-purpose, high-level programming language widely used in bioinformatics, molecular biology and Nasonia husbandry.

Training will also be provided in the preparation of NGS libraries. The student will also become conversant with general molecular biology techniques such as PCR, qPCR and cloning.

Partners and collaboration

This is a collaborative project between the lead supervisor Mallon and co-supervisor Kyriacou.  The supervisors have complimentary interests and expertise in hymenoptera, DNA methylation and diapause and of next generation sequencing techniques to investigate these areas. Mallon will provide specific expertise in the role of epigenetics, while Kyriacou is a leading expert on insect diapause. This proposal will benefit greatly from the ongoing collaboration between Mallon and Kyriacou in the neurogenetics group, e.g. joint weekly seminars.

Further details

Please contact Eamonn Mallon, Department of genetics and genome biology, University of Leicester, [email protected] for further details. https://www2.le.ac.uk/projects/selab

If you wish to apply to the project, applications should include:

  • A CV with the names of at least two referees (preferably three and who can comment on your academic abilities)

Applications to be received by the end of the day on Wednesday 11th January 2023. 

Possible timeline

Year 1

Whole genome bisulfite sequencing from non-diapaused adult to establish an epigenetic clock.

Year 2

Whole genome bisulfite sequencing from non-diapaused and diapaused larva.

Year 3

Whole genome bisulfite sequencing from diapaused adult.

Further reading

Journal:

  • Horvath, S. DNA methylation age of human tissues and cell types. Genome Biol 14, 3156 (2013). https://doi.org/10.1186/gb-2013-14-10-r115. The original paper that discovered epigenetic clocks in humans.
  • Pinho, G.M., Martin, J.G.A., Farrell, C. et al. Hibernation slows epigenetic ageing in yellow-bellied marmots. Nat Ecol Evol 6, 418–426 (2022). https://doi.org/10.1038/s41559-022-01679-1. A paper showing a very clear effect of mammalian hibernation on epigenetic ageing.

COVID-19

The lifespan experiments are the most sensitive to disruption. A large scale lockdown would see the student shift focus to the bioinformatic part of the project, either analysing their own sequencing or sequencing already available in the lab or publicly.