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Regulation of apoptosis-induced compensatory cell proliferation in tissue homeostasis and stress response

Principal Supervisor: Dr. Yun Fan - School of Biosciences

Co-supervisor: Dr. Neil Hotchin

PhD project title: Regulation of apoptosis-induced compensatory cell proliferation in tissue homeostasis and stress response

University of Registration: University of Birmingham

Project outline:

In multi-cellular organisms, coordinated cell death (e.g. apoptosis) and cell replacement is critical for tissue recovery in response to stress or damage. Although there is not much known about this process at the cellular and molecular level, recent studies including ours have discovered that apoptotic cells can actively induce compensatory proliferation of surrounding cells through a non-apoptotic function of caspases, a family of cysteine-proteases that normally execute apoptosis. This PhD project is designed to further dissect the molecular anatomy of compensatory cell proliferation in response to apoptosis. By using Drosophila as a model organism, combined approaches including genetic screening, molecular biology, immunohistochemistry, and proteomics will be employed to systematically identify and characterise novel regulators of apoptosis-induced cell proliferation at the molecular level. Because apoptosis-induced cell proliferation has been observed in maintenance of tissue homeostasis in multiple organisms including mammals, identification of its underlying regulatory mechanisms in Drosophila will significantly impact our understanding of its physiological role in tissue repair as well as its pathological role in multiple human diseases.

References:

  1. Li M., Lindblad J.L., Perez E., Bergmann A. and Fan Y. (2016). Autophagy-independent function of Atg1 for apoptosis-induced compensatory proliferation. BMC Biol. 14: 70.
  2. Fan Y.*, Wang S., Hernandez J., Yenigun V.B., Hertlein G., Fogarty C.E., Lindblad J.L. and Bergmann A. (2014). Genetic models of apoptosis-induced proliferation decipher activation of JNK and identify a requirement of EGFR signaling for tissue regenerative responses in Drosophila. PLoS Genetics 10 (1): e1004131. (*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
  • In vitro caspase cleavage assays
  • Mass spectrometry
  • Immunohistochemistry and high-resolution microscopy

Contact: Dr Yun Fan, University of Birmingham