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Thesis Defence

PhD degree for Andreas Kompatscher

AndreasPhD 12 Sep 2018

Andreas Kompatscher successfully defended his thesis entitled "Unlocking the doors of transcription: key transcriptional regulators in calcium and magnesium reabsorption".

 

Outline of this thesis

The aim of his thesis was to heighten our understanding of the transcriptional regulation behind Mg2+ and Ca2+ reabsorption in the kidney. Although much is known about the biochemical and molecular basis of Mg2+ and Ca2+ transport pathways and its regulatory networks, there is very few knowledge available on how Mg2+ and Ca2+ reabsorption is regulated at the transcriptional level. Despite the existence of several electrolyte disorders that are caused by transcription factors and their binding partners. Therefore, this thesis aimed to elucidate the transcriptional networks that regulate Ca2+ and Mg2+ reabsorption in the kidney. Chapter 2 provides a genome-wide assessment of all binding sites of transcription factor HNF1b in the DCT. An immortalized DCT cell line and a HNF1b renal knockout mouse was used to confirm our HNF1b candidate gene. These results contribute to a heightened understanding of the transcriptional regulation behind Mg2+ handling in the DCT. In chapter 3 we elucidated an additional novel binding partner of HNF1b in the TAL. We performed additional luciferase assays and siRNA knockdown experiments to confirm the transcriptional regulation of HNF1b on this target gene. This study revealed HNF1b as a novel transcriptional activator of Mg2+ and Ca2+ transport in the TAL. Chapter 4 investigates the function of nuclear protein FAM111a in renal Mg2+ transport. Both RNA-sequencing and GFP-pulldown experiments were used to identify transcriptional targets and binding partners. These findings contribute to a better understanding of the renal electrolyte phenotype in FAM111a patients and could lead to potential new treatments for Kenney-Caffey type 2 syndrome patients. In chapter 5 we characterized the P2x6 KO mouse investigating its potential renal electrolyte phenotype by performing metabolic cage experiments and subsequent screening of magnesiotropic genes with real-time quantitative-PCR (RT-qPCR). In chapter 6 the findings of this thesis are summarized and further discussed by placing them in the context of current knowledge on the transcriptional regulation behind Mg2+ and Ca2+ transport in the TAL and DCT.

Click here to access Andreas' thesis digitally.

 

 

 


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