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Title: Exploring inter-organ signaling in Drosophila
Authors: Lopes, Tatiana Raquel Gonçalves
Advisor: Aliaga, Irene Miguel
Keywords: Drosophila
nutrient sensor
mini-white gene
Issue Date: 2-May-2019
Abstract: The gut is already known to be an important nutrient-sensing endocrine organ, with the capacity of regulating its own functions and influencing the roles of other organs. Previous work in the Lab focused on the characterization of a novel nutrient sensor expressed in the Drosophila midgut ECs, more specifically, interstitial cells. Deletion or knockdown of this sensor from these cells, leads to, among other phenotypes, a developmental delay that is exacerbated in poor nutritional conditions, hence, being defined as a nutrient sensor. Apart from being responsive to nutritional cues, prior experiments found this sensor to be a pH sensitive chloride channel gated by zinc, and was named hodor. My project aimed to continue this work in order to contribute to the further understanding of inter-organ signaling, by addressing several questions related to hodor, like finding which component is responsible for the phenotypes exacerbation under poor nutritional conditions, as well as, to identify transcripts whose expressions changes in response to Hodor activity. I was able to partially rescue two of hodor mutant phenotypes through food supplementation, as well as giving preliminary data that supports the rescue of a third phenotype. Together with experiments performed by my supervisor, my data supports a model whereby, in the absence of hodor, the interstitial cells experience an osmotic shift that prevents the release of signals required to regulate food intake and results in a delay in development. Furthermore, I highlighted four candidate genes whose expression is altered in hodor mutant larvae, for future investigation into the mechanisms controlling hodor function. Throughout my project I came across other novel findings not directly associated with hodor. I have shown that the mini-white gene, a truncated form of the white gene encoding an ATP-binding cassette (ABC) transporter in Drosophila, influences developmental timing. I discovered that introducing the mini-white gene in an otherwise mutant white fly leads to faster pupariation time, thus, faster development. Moreover, I also found that larvae and adults seem to have different location to store zinc within the intestine. Although hodor is not conserved in mammals, it is present in the mosquito species responsible for malaria transmission (Anopheles gambiae). This makes it a potential target for biotechnology approaches aiming to control mosquito populations in the wild. Simultaneously, since Hodor is a nutrient sensor that is mainly present in the midgut enterocytes, understanding its mechanism is also important to increase our knowledge about how ECs sense nutrients and how they communicate with other cells/organs, thus, contributing to our understanding of the gut response to the diet.
Description: Dissertação de Mestrado em Biotecnologia para as Ciências da Saúde
Document Type: Master Thesis
Appears in Collections:DGB - Dissertações de Mestrado
TD - Dissertações de Mestrado

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