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Bio4med | Research Projects

This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie COFUND grant agreement No 665735.

Bio4Med Research Projects:


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15: Bio4Med - Metabolic regulation of the DNA damage response in pancreatic beta cells in different models of type 2 diabetes
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Supervisor:
prof. Agnieszka Dobrzyn
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Foreign partner:
Dr Harini Sampath, Oregon Health and Science University, Portland, USA
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WWW
http://team.nencki.gov.pl/
Background:
Pancreatic islet/beta cell failure is central to the onset and progression of diabetes. Oxidative stress associated with metabolic dysfunction significantly contributes to beta cell injure and type 2 diabetes development. Cellular components, including DNA, are subject to oxidative damage. If left unrepaired, this damage can lead to multiple adverse cellular outcomes, including increased mutagenesis and cell death. The major pathway for repair of oxidative base lesions is the base excision repair pathway, catalyzed by DNA glycosylases with overlapping but distinct substrate specificities. The objective of the Project is to determine the effect of impaired cell metabolism on DNA damage repair pathways in pancreatic islets during the progression of type 2 diabetes. Experiments will be carried out in vivo on different genetic and dietary models of obesity-related type 2 diabetes and in vitro on pancreatic beta cell line. Transient overexpression and siRNA technology will be used to specifically affect expression of key metabolic genes and transcription factors. To asses DNA damage repair functional genomics and biochemical approaches will be employed.
Aim:
To determine the effect of impaired cell metabolism on DNA damage repair pathways in pancreatic islets during the progression of type 2 diabetes.
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