Establishing an insect model for epigenetic diseases

Qualification: PhD

Department: Genetics

Application deadline: 31 May 2021

Start date: 27 September 2021

Overview

Supervisors:

Dr Eamonn Mallon and  Professor Flaviano Giorgini

Project description:

Epigenetics is defined as the heritable change in expression of a gene without any change in the DNA sequence. It is important in fields as diverse as human cancer biology and the ecological response of animals and plants to environmental pollutants. The methylation of the fifth position of DNA’s cytosine’s ring is one of the most widespread epigenetic markers.


The study of epigenetics has for the most part been correlational. A common correlational research strategy is to examine the methylation differences between two phenotypes and hypothesise that the differences found are the causes of the phenotype. What is rarer is a strategy analogous to reverse genetics, whereby the methylation of an organism is changed, and the resultant phenotype studied to confirm methylation’s role.
Until recently, what reverse epigenetics there has been of a general, crude sort. For example, early studies of the role of methylation in mammalian development, simply knocked out DMNT3, the enzyme responsible for the production of new methylation marks. This reduced the methylation throughout the embryo’s genome and the resultant phenotype was measured. Other studies decreased total genomic methylation by the use of drugs such as 5-aza-2’-deoxycytidine. This has now all changed with the use of the CRISPR system to alter the methylation levels at a single locus.

Simple insect models are needed to understand complicated biological processes. The parasitic wasp Nasonia vitripennis is a prime contender as an insect model species for epigenetics. The fruit fly, Drosophila melanogaster, has long been the predominant insect model for genetics. However, Drosophila, for the most part, lacks CpG methylation. Nasonia, like other hymenoptera, has a functional methylation system. Nasonia replicates many of the abilities of the Drosophila model, namely it is easily maintained in a laboratory environment due to its short generation time (approximately 2 weeks) and ease of rearing. Its genome has been sequenced and many molecular tools are now available for this species. Recently, CRISPR/Cas9 technology has been used to induce site specific mutations on the cinnabar (cinnabar) gene in N. vitripennis adding a new powerful molecular tool for reverse genetics for this insect. 
In this project you will identify candidate genes for various epigenetic diseases. You will then alter their methylation status using CRISPR technology and record their phenotype using a series of assays.

Merely as an example, consider cancer. The development of human cancer is a multistep process, involving changes in signalling, cell-cycle and cell-death pathways, as well as interactions between the tumour and the tumour microenvironment. To dissect the steps of tumorigenesis, simple animal models, such as insect models are needed. Changes in methylation are a fundamental part of cancer development. This project will develop a system to allow changes in methylation status on a given gene in an insect model. This could lead to an insect model for cancer epigenomics, a major step forward in the field.

Mukherjee et al (2015) Insects as models to study the epigenetic basis of disease, Progress in Biophysics and Molecular Biology, Volume 118, Issues 1–2, Pages 69-78. https://doi.org/10.1016/j.pbiomolbio.2015.02.009

Funding

Funding

The Studentship provides:

  • 3 Years of stipend at UKRI rates

  • 3 Years tuition fees at UK rates

Entry requirements

Entry requirements

UK Bachelor Degree with at least 2:1 in a relevant subject or overseas equivalent.

The University of Leicester English language requirements apply where applicable.

Informal enquiries

Informal enquiries

Project enquiries to Dr Eamonn Mallon emb3@le.ac.uk 

Application enquiries to pgradmissions@le.ac.uk

How to apply

How to apply

To submit your application, please use the Apply button at the bottom of the page and select September 2021 from the dropdown menu.

With your application, please include:

  • CV
  • Personal statement explaining your interest in the project, your experience and why we should consider you
  • Degree Certificates and Transcripts of study already completed and if possible transcript to date of study currently being undertaken
  • Evidence of English language proficiency if applicable
  • In the reference section please enter the contact details of your two academic referees in the boxes provided or upload letters of reference if already available
  • In the funding section please specify that you wish to be considered for the GGB Mallon 2021 studentship
  • In the research proposal section please provide the names of the project supervisors and project title (a research proposal is not required)

Eligibility

Eligibility

This PhD studentship is available to UK/EU applicants only.