In silico analysis of enteroendocrine cell size in Drosophila with altered NAD+/NADH redox balance
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Journal Title
Journal ISSN
Volume Title
Kemian tekniikan korkeakoulu |
Master's thesis
Author
Date
2024-06-17
Department
Major/Subject
Biosystems and Biomaterials Engineering
Mcode
CHEM3028
Degree programme
Master’s Programme in Life Science Technologies
Language
en
Pages
71
Series
Abstract
Enteroendocrine cells (EECs) are vital components of the body endocrine system. They play a key role in the regulation of metabolism, digestion, and overall homeostasis through hormone secretion in response to nutritional and environmental signals. However, the precise molecular mechanisms which underpin the function and fate of EECs remain largely unknown. Previous work in the Hietakangas lab has identified a major regulator of EEC function: the transcription cofactor C-terminal binding protein (CtBP). Mechanistically, CtBP senses changes in the redox balance of nicotinamide adenine dinucleotides (NAD+/NADH) within EECs induced by dietary alterations and translates them into specific transcriptional programs that determine cell fate and growth. This study investigates potential connections between altered NAD+/NADH redox balance, hormonal signalling, diet, and EEC size. To accomplish this aim and analyse the size of EEC upon genetic alterations of CtBP-dependent target proteins, a machine learning-based image analysis pipeline was developed. The findings of the study indicate that CtBP and its transcriptional targets have a significant impact on EEC growth, generally promoting enlargement of EECs. Limitations of this study include variations in image quality and the need for mechanistic validation. Broadly, I conclude that sugar availability may determine EEC size in part via the redox-sensitive transcription cofactor CtBP and its associates.Description
Supervisor
Kostiainen, MauriThesis advisor
Hietakangas, VilleRovenko, Bohdana
Keywords
Drosophila, enteroendocrine, nutrient sensing, CtBP
