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

This project will help understand why organisms age differently by establishing the effect of early life environments on epigenetic ageing in the model insect, Nasonia vitripennis. How individuals and species age so differently is one of the major unanswered questions in evolutionary biology with early life environments being a major predictor of lifespan.  

Ageing is a mechanistically complex process influenced by many environmental and genetic com- ponents. The effects of these components influence each other, making them difficult to investigate, especially in complex mammalian models. Therefore, a large body of ageing research is based on simple model invertebrate organisms. Advantages include easy and inexpensive to keep in a laboratory, short life span, genetic and molecular tools available, and a sequenced genome.  

However, current invertebrate ageing models (Drosophila and C. elegans) do not possess certain chemical marks (DNA methylation), an important part of how most organisms age. An epigenetic clock is a biochemical test based on measuring the accumulation of this DNA methylation. There is evidence that epigenetic clocks mirror true biological age and its associated morbidity and mortality better than chronological age in many species including us.  

The jewel wasp, Nasonia vitripennis, an emerging model, has a functional methylation system, making it an ideal species to investigate the epigenetics of ageing. We have established an epige- netic clock in this species.  

Early life effects on ageing have pervasive influence on the ecology and evolution of a range of species from fish to birds to humans. It would be useful to study a dramatic example, where a distinct early life environment lead to a dramatic switch in ageing strategy, a so-called senescence plasticity. An example of this is larval diapause in Nasonia where if the mother experiences autumn-like conditions, her larval offspring become dorminant over winter and then as adults live much longer than adult Nasonia who haven’t overwintered.  

Photos of the same man ageing from young adulthood to late middle age.

Figure 1: Early life environments seem to be one of the most important factors in how an organism ages. 

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 Nasonia, machine learning, RNAi knockdowns of methylation enzymes and high-throughput behavioural analysis, to analyse chrono- logical and 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 in R, a statistical programming language, Python, a general-purpose, high-level programming language widely used in bioinformatics, molecular biology, RNAi, behavioural analysis and Nasonia husbandry as required.  

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

Further details on how to contact the supervisor for this project and how to apply for this project can be found here: 

For any enquiries related to this project please contact Eamonn Mallon, [email protected].  https://www2.le.ac.uk/projects/selab.  

To apply to this project: 

  • You must include a CENTA studentship application form, downloadable from: CENTA Studentship Application Form 2024. 
  • You must include a CV with the names of at least two referees (preferably three) who can comment on your academic abilities. 
  • Please submit your application and complete the host institution application process via: https://le.ac.uk/study/research-degrees/funded-opportunities/centa-phd-studentships.  Please scroll to the bottom of the page and click on the “Apply for NERC CENTA Studentship” button.  Your CV can uploaded to the Experience section of the online form, the CENTA application form 2024 can be uploaded to the Personal Statement section of the online form.  Please quote CENTA 2024-L4-CENTA2-GENE1-MALL  when completing the application form. 

Applications must be submitted by 23:59 GMT on Wednesday 10th January 2024. 

Possible timeline

Year 1

Analyse the survivorship and behaviour of non-diapaused and diapaused adult Nasonia  in order to measure the effects of larval diapause on the lifespan and healthspan of adults.

Year 2

Analyse whole genome bisulfite sequencing libraries from non-diapaused and diapaused adult Nasonia from eight timepoints in order to discover if larval diapause alters adult epigenetic ageing.

Year 3

Analyse the survivorship, behaviour and whole genome bisulfite sequencing libraries from diapaused Dnmt3 knockdown Nasonia and diapaused control knockdown Nasonia over eight timepoints in order to experimentally induce changes in genome-wide DNA methylation in diapaused Nasonia and measure their effects.

Further reading

  • 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. 
  • Brink K., Thomas C., Jones A. , Mallon E.B. An epigenetic clock in an insect model system bioRxiv 2023.02.14.528436. https://doi.org/10.1101/2023.02.14.528436. Our preprint with the discovery of an insect epigenetic clock.