2026-09-18T19:02:52Zhttps://api.repository.cam.ac.uk/server/oai/requestoai:www.repository.cam.ac.uk:1810/2919062021-04-21T19:44:17Zcom_1810_221629com_1810_34581col_1810_221630
Drosophila melanogaster as a high-throughput and in vivo model to study body weight and feeding behaviour
10.17863/CAM.39064
Chalmers, Jennifer
Yeo, Giles
Obesity and its associated comorbidities represent one of the greatest public health challenges
of the 21st century. Whilst the increase in prevalence has been driven by changes in lifestyle
and environment, it is clear that there is a genetic component underlying the variation in
body weight between individuals. However, the speed of translating obesity genetics into
insightful biological knowledge has not kept pace with the rate of identification of potential
genes of interest. One reason for this is that studies have so far been addressed in complex
model organisms such as mice.
Drosophila melanogaster is a key model for research in developmental biology, cell
biology and neurobiology, and has also recently been demonstrated to be an excellent model
for dissecting metabolic homeostasis pathways. In this thesis, a suite of assays was developed
in Drosophila to examine changes in the state of energy homeostasis and changes in energy
intake in response to specific genetic perturbations. This screen was validated by its ability
to detect metabolic perturbation in wild-type flies, and to differentiate between positive and
negative control genes. Different Drosophila models were investigated for their suitability
for the screen, and neuron-specific RNAi was found to provide the most useful information.
CRISPR was also investigated as a method of generating mutations in target genes de novo.
The validated screen was then used to explore genes highlighted by GWAS studies of
human body mass index (BMI), and by transcriptomics studies of fasted mouse hypothalamic
neurons. Each of these screens identified some genes which are already known to play an
important role in the control of energy homeostasis in mammals, demonstrating that the
screen is able to produce relevant results. They also highlighted several genes for which
there is currently no published functional data, demonstrating the utility of Drosophila in a
high-throughput screen to assay the potential involvement of genes in the neuronal control of
food intake and body weight.
University of Cambridge
2019-05-18
Thesis
Doctoral
Doctor of Philosophy (PhD)
en
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Obesity
genetics
Drosophila
GWAS
RNAseq
Screen