How Cell Death Fuels Growth

Secondary Supervisor(s): Professor Chris Bunce

University of Registration: University of Birmingham

BBSRC Research Themes: Integrated Understanding of Health (Regenerative Biology)

Project Outline

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.

References

Farrell L, Puig-Barbe A, Haque MI, Amcheslavsky A, Yu M, Bergmann A and Fan Y (2022). Actin remodeling mediates ROS production and JNK activation to drive apoptosis-induced proliferation. PLoS Genet 18(12): e1010533.

Hounsell C and Fan Y (2021). The Duality of Caspases in Cancer, as Told through the Fly. Int J Mol Sci 22(16): 8927.