Developing a Drosophila model of radiation induced toxicity to identify risk loci

Trinca, Terrence 2022. Developing a Drosophila model of radiation induced toxicity to identify risk loci. PhD Thesis, Cardiff University. Item availability restricted.

Preview	PDF (PhD thesis) - Accepted Post-Print Version Download (10MB) | Preview
	PDF (Cardiff University Electronic Publication Form) - Supplemental Material Restricted to Repository staff only Download (4MB)

Abstract

Humans are becoming increasingly more exposed to radiation through medical treatment such as radiotherapy, occupational hazard, environmental exposure, and travel at high-altitude or space flight. The long-term consequences of radiation exposure/treatment are poorly understood, with the field of radiobiology currently lacking any pre-clinical models. Drosophila melanogaster offers to be an enticing in vivo pre-clinical model to better understand the radiation response, largely due to its short lifespan, genetic tractability and affordability of research. The work presented here highlights efforts to develop a Drosophila model for long-term radiation-induced tissue toxicity. Initial work involved characterising Drosophila response to radiation using various metric of overall health such as lifespan, fertility and movement assaying. Subsequent work identified tissue specific sensitivity to radiation treatment, as observed in humans, in particular the midgut was identified as a sensitive organ. Further, it was shown that the midgut underwent systemic remodelling and sustained oxidative stress which persists long-term post radiation treatment. Drosophila were then used to identify genetic loci associated with the radiation response. To do this, an RNA-seq experiment was performed which quantified the transcriptome of various adult tissues (e.g. midgut, brain, muscle and fat body) post irradiation. For each tissue there were many differentially expressed genes, and subsequent analysis identified a subset of 19 genes which were differentially expressed in all tissues – a conserved signature of irradiation. Additional to employing genome-wide approaches, a candidate approached was performed on a select number of genes, to try and functionally validate their role in modulating radiation sensitivity in Drosophila. This work highlights the need and the success of a Drosophila radiation response model. RNA-seq analysis has identified many loci that have yet to be functionally validated, and as majority of these loci have human orthologues, their functional validation may help to elucidate the underlying mechanisms of long-term radiation�induced tissue toxicity in humans

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Biosciences
Subjects:	Q Science > Q Science (General)
Date of First Compliant Deposit:	7 November 2022
Last Modified:	10 Jun 2023 01:53
URI:	https://orca.cardiff.ac.uk/id/eprint/154017

Actions (repository staff only)

Edit Item