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Torunn Bruland; post doc NTNU, DMF. Gene regulation in biological responses: Focus on gastrin responses in neuroendocrine cells in the gastro-intestinal tract. Studies of early retrovirus-host interactions. Viral determinants for pathogenesis
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Torunn Bruland; post doc NTNU, DMF Gene regulation in biological responses: Focus on gastrin responses in neuroendocrine cells in the gastro-intestinal tract
Studies of early retrovirus-host interactions Viral determinants for pathogenesis and the influence of sex on the susceptibility to Friend murine leukaemia virus infection Dr. philos thesis 2003; NTNU, Faculty of Medicine • ANIMAL MODEL (mice) • virology • immunology • cell biology • signal transduction • molecular biology • statistic
Molecular mechanisms in the normal and diseased gastrointestinal system Normal Early gastric cancer Adenocarsinoma
Gene regulation in biological responses: Focus on gastrin responses in neuroendocrine cells in the gastro-intestinal tract Enterochromaffin-like (ECL) cells are a distinctive type of neuroendocrine cells in the gastric mucosa underlying the epithelium Introduction Longer term stimulation of ECL cells by gastrin stimulates significant proliferation of ECL cells
Several gastrin responsive genes contain cAMP responsive promotor element (CRE)
Modulation of gastrin-mediated gene expression by transcriptional regulators of the CREB/CREM/ATF family
Work plan: cDNA/oligo/splice variant MIKROARRAY • gastric carsinoma • gastric carcinoids • hypergastrinemia • gastrin-mediated gene expression • CREB/CREM/ATF-modulated • gene expression • Genome-wide gene expression • gastric mucosa custom microarrays • system-wide screening of CREB/CREM/ATF splice variants
Hypothesis testing: high throughput/single gene Reverse Transfection RNAi + Microarray
Summary • gastrin-mediated gene expression • CREB/CREM/ATF-modulated • gene expression • High throughput • 96-well • array based • Single gene • knock-up • knock-down • (RNAi) • animal models • Genome-wide gene expression • gastric mucosa custom microarrays • system-wide screening of CREB/CREM/ATF • splice variants • statistical methods for: • preprocessing and discrimination and classification • rule-based methods for classification • optimal use of biological background knowledge
Gene regulation in biological responses: Focus on gastrin responses in neuroendocrine cells in the gastro-intestinal tract Prosjektansvarlig Astrid Lægreid, professor, dr.scient., Prosjektmedarbeidere Liv Thommesen, førsteam.. dr.philos., HiST Torunn Bruland, post.doc. dr.philos., IKM, NTNU Ola Ween, post.doc. dr.scient., IKM, NFR Kristine Misund, cand.scient. NTNU Tonje Strømmen, siv.ing. NTNU