Investigating the role of F-actin polymerisation in Apoptosis-induced Proliferation

Farrell, Luchi James (2019). Investigating the role of F-actin polymerisation in Apoptosis-induced Proliferation. University of Birmingham. Ph.D.

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Abstract

Apoptosis-induced proliferation (AiP) is a recently defined phenomenon where dying cells can contribute towards non-cell-autonomous proliferation. Studies in the genetic model Drosophila melanogaster have provided great insight into the process of AiP. Induction of AiP in Drosophila relies upon activation of the initiator caspase Dronc, followed by the production of reactive oxygen species (ROS) and activation of stress responder c-Jun N-terminal kinase (JNK). Signal propagation results in the release of various mitogenic factors including Wnt orthologue Wingless (Wg), TGF-β orthologue Decapentaplegic (Dpp) and EGF orthologue Spitz (Spi), causing proliferation in neighbouring tissue. However, the mechanistic details that underlie AiP, such as how Dronc activates JNK are largely unknown. Recent developments in the field, have shown that Dronc subcellular localisation to the plasma membrane, is an important event in coordinating AiP propagation. Furthermore, previous identification of small GTPase Rho1 (RhoA orthologue), suggests that cytoskeletal regulation could be an important event in AiP induction. The work presented in this thesis investigates the hidden potential of F-actin regulation during AiP and focuses on two key regulators identified, exploring their crucial functions in mediating AiP.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):