Primary Supervisor: Dr Yun Fan, School of Biosciences
Secondary supervisor: Prof Chris Bunce
PhD project title: Understanding life after cell death
University of Registration: University of Birmingham
Apoptosis, a major form of programmed cell death, is frequently activated in response to stress to remove damaged cells in multi-cellular organisms. It is therefore the guardian of health. However, it has long been a mystery how tissue recovers after damaged cells are removed. Work by us and others has revealed that, surprisingly, apoptotic cells can actively promote compensatory proliferation of their neighbouring cells to maintain tissue homeostasis, a process termed Apoptosis-induced Proliferation (AiP). Recent studies in several organisms including Drosophila and mammals have revealed that AiP plays critical roles in tissue recovery and regeneration and, in pathological conditions, uncontrolled AiP can lead to excessive tissue overgrowth. Yet there is not much known about regulation of AiP at the cellular and molecular level. This PhD project is designed to further dissect the molecular anatomy of AiP. By using Drosophila as a model organism, combined approaches including genetic epistasis, molecular biology, proteomics, immunohistochemistry, advanced microscopy and quantitative data analysis will be employed to systematically identify and characterise novel regulators of AiP. As AiP is evolutionary conserved, this project will make substantial contributions to our understanding of the cellular strategies and the genetic pathways used to maintain tissue homeostasis and promote tissue repair.
- Amcheslavsky A., Wang S., Fogarty C., Lindblad J.L., Fan Y. & Bergmann A. (2018). Plasma membrane localization of apoptotic caspases for non-apoptotic functions. Developmental Cell 45: 450-464.
BBSRC Strategic Research Priority: Integrated Understanding of Health: Regenerative Biology
Techniques that will be undertaken during the project:
Drosophila genetics, epistasis analysis, statistics, 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