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Dissecting the importance of epigenetic modifiers for immune regulation of muscle regeneration

*Please note this project is self-funded*

Project details

 
1st supervisor: Dr. Robert Knight
2nd supervisor: Dr. Fiona Wardle
Eligibility: Home/EU
Funding: Self-funded
Start date: 1 October 2017
Application deadline: 28 February 2017
Reference number:2017/DI/02

Project description

This proposal aims to use a zebrafish model of muscle regeneration in order to identify the importance of epigenetic signals for controlling how the immune system responds to tissue injury and modulates muscle repair. The purpose is to determine which chromatin modifying proteins regulate the response of immune cells to muscle injury and how this is important for muscle stem cell-mediated regeneration.

Specific Aims to be tested include:

  1. determine the importance of EZH2 function for controlling inflammatory response to tissue injury 
  2. evaluate the importance of TNF signaling for regulating inflammatory cell and muSC responses to injury
  3. functionally test whether EZH2 acts to potentiate responses of inflammatory cell  and muSCs to TNF signaling. 

To address these aims we will use transgenic zebrafish for gene over-expression and visualisation of cells during regeneration. Imaging of cell responses to injury will be performed by confocal and multiphoton microscopy. TNF signaling and EZH2 function will be manipulated by genetic, pharmacological and over-expression techniques. To measure chromatin changes in muSCs and inflammatory cells in response to altered TNF or EZH2 function, RNA-SEQ and ChIP-SEQ will be performed on cells isolated by flow cytometry.

Candidate genes regulated by EZH2 and TNF in muSCs and inflammatory cells will be identified using computational analyses of ChIP-SEQ and RNA-SEQ data. Selected candidate genes will then be tested for their role in controlling inflammatory cell and muSC responses to injury by over-expression under the control of cell specific promoters and cell behaviour analysed by live cell imaging.

To view entry requirements and fee information, see the Dental and Health Sciences Research MPhil/PhD

 

Next steps

How to apply

Please apply online at https://apply.kcl.ac.uk/ following these steps:

  1. Register a new account/login
  2. Open a new application
  3. Under Choose a programme:
    1. Programme type: Research programme
    2. Faculty name: Dental Institute
    3. Award type: Research degree
    4. Select ‘Dental and Health Sciences Research MPhil/PhD (Full-time)
    5. Select September 2017 as the start date (for 1 October 2017 start)

Please note: Applicants must include the project reference number in the 'Research proposal' section of their application.

Contact for further information
Informal enquires can be sent to Dr. Knight (robert.knight@kcl.ac.uk) or Dr. Wardle (fiona.wardle@kcl.ac.uk). 
 

Related division Craniofacial Development and Stem Cell Biology.

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