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Deciphering the regulation of necrosis

Primary Supervisor: Dr Yun Fan, School of Biosciences

Secondary supervisor: Dr Nik Hodges

PhD project title: Deciphering the regulation of necrosis

University of Registration: University of Birmingham

Project outline:

Necrosis is a type of premature cell death frequently caused by excessive insults such as trauma, infection and toxins. Unlike apoptosis, a major form of programmed cell death, necrosis has long been considered to be passive and uncontrolled. However, recent studies have revealed that certain types of necrosis can be genetically controlled thus regulated. This has attracted growing interests to decipher regulation of necrosis because it may provide therapeutic targets for many human diseases including neurodegenerative disorders and inflammatory diseases. However, our knowledge about regulation of necrosis is still very limited. This is partly due to lack of in vivo assays for systematic analyses. To address this, we have recently established a model of regulated necrosis controlling neuronal death in Drosophila, an organism with advantages of genetic manipulation. Intriguingly, our study has revealed that a strong analogy exists between mammals and Drosophila in regulation of necrosis. It is therefore feasible to use Drosophila assays to further dissect regulation of necrosis in vivo. 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:

  1. Li M., Sun S., Priest J., Bi X. & Fan Y. (2019). Characterization of TNF-induced cell death in Drosophila reveals caspase- and JNK-dependent necrosis and its role in tumor suppression. Cell Death & Disease 10: 613.

BBSRC Strategic Research Priority: Understanding the Rules of Life: Neuroscience and behaviour

    Techniques that will be undertaken during the project:

    • Drosophila genetics
    • Epistasis analysis
    • Molecular cloning
    • Sequencing
    • qRT-PCR
    • Western blots
    • Immunohistochemistry
    • High-resolution microscopy
    • Screening
    • Statistics

    Contact: Dr Yun Fan, University of Birmingham