Understanding regulated necrosis using Drosophila as a model organism

Sun, Shiyao (2021). Understanding regulated necrosis using Drosophila as a model organism. University of Birmingham. Ph.D.

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Abstract

Necrosis is often associated with diseases, and it was believed to be a form of accidental cell death for a long time. Recent studies have shown that some specific types of necrosis are molecularly controlled therefore regulated. However, its underlying mechanisms are poorly understood. In my PhD project, I examined the molecular mechanisms of necrosis induced by Eiger (Egr), the Drosophila homolog of the tumour necrosis factor α (TNFα). I showed that the c-Jun N-terminal kinase (JNK), a stress-response molecule, and the initiator caspase Dronc, a protease known for its role in activating apoptosis, are both required and sufficient to induce necrosis. Moreover, I conducted a genetic screen to identify novel regulators of Egr-induced necrosis, which discovered roles of reactive oxygen species (ROS) and Sima, the Drosophila homolog of the hypoxia inducible factor-1α (HIF-1α) in necrosis. Further genetic analyses suggested that Sima acts upstream of ROS in mediating Egr-induced necrosis.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):