Project highlights

  • Epigenetic Aging Research with Insect Model: This project aims to uncover how organisms age by using an insect model, Nasonia vitripennis, which possesses a functional methylation system. The research will explore the relationship between development and aging by analyzing epigenetic dynamics during diapause, a state of arrested development that has been shown to increase lifespan in insects. 
  • Testing the Programmatic Theory of Aging: The project will test hypotheses related to the programmatic theory of aging, which suggests that aging is a continuation of developmental processes. It will specifically examine whether genes affected by diapause or rapamycin treatment during development are the same as those affected during aging, providing insights into the mechanisms linking development and aging. 
  • Innovative Methodology Combining Genomic and Transcriptomic Analysis: The project employs a combination of whole genome bisulfite sequencing (BS-seq) and RNA-seq to analyze changes in DNA methylation and gene expression across different life stages of Nasonia. This approach will help identify the genetic and epigenetic factors that contribute to aging and how they are influenced by developmental arrest and pharmacological interventions like rapamycin. 

Overview

This project delves into the relationship between diapause—a developmental arrest induced by environmental cues—and ageing, using the insect model Nasonia vitripennis. Ageing is a critical biological process with broad implications for ecosystems and the natural environment. The research aims to explore whether ageing is a programmed process driven by genetic and epigenetic mechanisms or merely the result of incidental damage accumulated over time. 

Central to this study is the programmatic theory of ageing, which posits that ageing results from developmental programs that are beneficial early in life but become detrimental later. This theory can be seen as a mechanistic version of the antagonistic pleiotropy theory, which suggests that genes advantageous during early life may have adverse effects in later stages. Diapause, a natural adaptation to environmental stressors such as seasonal changes, offers an ideal context to explore this theory. By pausing development, diapause allows organisms to survive unfavorable conditions, and preliminary findings indicate that Nasonia adults that underwent larval diapause exhibit a significant increase in lifespan compared to those that did not. This suggests a strong link between environmental adaptation and longevity. 

The study focuses on the epigenetic changes that occur during diapause and how these changes influence the ageing process, providing insights into how environmental factors regulate essential biological processes. By investigating these molecular mechanisms, the research will enhance our understanding of how developmental programs extend into adulthood, potentially driving the ageing process. 

The project examines the similarities in gene expression changes during diapause and adult ageing, potentially identifying genetic pathways involved in both development and ageing. This could provide valuable insights into how organisms maintain resilience and adapt to changing environmental conditions over their lifespan. 

By testing the effects of rapamycin—a compound known to extend lifespan by mimicking diapause-like effects—the research highlights how external influences can modulate ageing, reinforcing the idea that environmental factors play a crucial role in shaping biological outcomes. 

This project integrates environmental biology, genetics, and epigenetics to address key questions about the relationship between development, ageing, and environmental adaptation, contributing to a broader understanding of how organisms respond to and are shaped by their environments. 

Close-up of a black insect (Nasonia vitripennis)

Figure 1: Nasonia vitripennis, a new model for epigenetic ageing. 

Host

University of Leicester

Theme

  • Organisms and Ecosystems

Supervisors

Project investigator

Co-investigators

How to apply

Methodology

The methods of the study involve using advanced genetic and molecular biology techniques to analyze the impact of diapause and rapamycin on epigenetic aging in the wasp Nasonia vitripennis. Specifically, the PhD candidate will conduct whole genome bisulfite sequencing (BS-seq) to measure DNA methylation at single-base resolution across the genome at various time points in diapaused and non-diapaused adult wasps. Additionally, RNA sequencing (RNA-seq) will be used to examine gene expression changes during different life stages (embryo, larva, pupa, and adult) under diapause and rapamycin treatments. Bioinformatic analyses will be performed to identify differentially methylated regions and gene expression patterns, allowing the team to test hypotheses related to the programmatic theory of aging. 

Training and skills

DRs will be awarded CENTA Training Credits (CTCs) for participation in CENTA-provided and ‘free choice’ external training. One CTC can be earned per 3 hours training, and DRs must accrue 100 CTCs across the three and a half 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, next-gen sequencing, 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

Please contact Eamonn Mallon, Department of Genetics, Genomics and Cancer Sciences, University of Leicester, [email protected] for further details. https://le.ac.uk/people/eamonn-mallon.

To apply to this project:  

  • 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: CENTA PhD Studentships | Postgraduate research | University of Leicester.  Please scroll to the bottom of the page and click on the “Apply Now” button.  The “How to apply” tab at the bottom of the page gives instructions on how to submit your completed CENTA Studentship Application Form 2025, your CV and your other supporting documents to your University of Leicester application. Please quote CENTA 2025-L9 when completing the application form.  

Applications must be submitted by 23:59 GMT on Wednesday 8th January 2025.  

 

Possible timeline

Year 1

Analyse BS-seq libraries from non-diapaused and diapaused adult Nasonia from eight time-points in order to discover if larval diapause alters adult epigenetic ageing.

Year 2

Analyse RNA-seq libraries of non-diapaused and diapaused Nasonia at each developmental stage and during adult ageing in order to discover if the genes whose activity is affected by diapause during development are the same genes affected by diapause during adult ageing. 

Year 3

Analyse RNA-seq libraries of control and rapamycin treated Nasonia at each developmental stage and during adult ageing in order to discover if manipulating ageing with rapamyacin will affect the same gene expression changes mediated by diapause. 

Further reading

Journal:  

  • 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.L., Jones, A. et al. Exploring the ageing methylome in the model insect, Nasonia vitripennis. BMC Genomics 25, 305 (2024). https://doi.org/10.1186/s12864-024-10211-7 Our paper with the discovery of an insect epigenetic clock.