Gene regulation in biological responses:

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Gene regulation in biological responses: 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

Gene regulation in biological responses

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

Generation of models

Reverse Transfection RNAi + Microarray Hypothesis testing: high throughput/single gene Reverse Transfection RNAi + Microarray

Summary gastrin-mediated gene expression CREB/CREM/ATF-modulated 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