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Determining novel molecular regulators of necrosis controlling neuronal cell death

Principal Supervisor: Dr Yun Fan - School of Biosciences

Co-supervisor: Dr Saverio Brogna

PhD project title: Determining novel molecular regulators of necrosis controlling neuronal cell death

University of Registration: University of Birmingham

Project outline:

Multiple forms of programmed cell death have been discovered in the past four decades. Among these, apoptosis is the most studied so far with evolutionarily conserved regulatory machineries reported. Recently, regulated necrosis, another type of programmed cell death, has been identified as an alternate to kill cells especially in pathological conditions when apoptosis is defective. However, our knowledge about regulation of necrosis is still very limited which is partly due to lack of in vivo assays for systematic analyses. To address this, we have established a model of regulated necrosis controlling neuronal death in Drosophila, an organism with advantages of genetic manipulation. Intriguingly, our study has revealed the analogy of necrosis regulation in Drosophila with its mammalian counterpart suggesting the feasibility of using Drosophila models to further dissect regulation of necrosis. This PhD project is an initiative to systematically identify and characterise novel regulators of necrosis in an intact organism and explore their roles in controlling neuronal cell death.

References:

Fan Y.* and Bergmann A. (2014). Multiple mechanisms modulate distinct cellular susceptibilities towards apoptosis in the developing Drosophila eye. Dev Cell, 30(1):48-60. (*corresponding author)

BBSRC Strategic Research Priority: Molecules, cells and systems

Techniques that will be undertaken during the project:

  • Drosophila genetics
  • Epistasis analysis
  • Mutation mapping
  • Molecular cloning
  • Sequencing
  • qRT-PCR
  • Western blots
  • Immunohistochemistry and high-resolution microscopy

Contact: Dr Yun Fan, University of Birmingham