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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.

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Presentation on theme: "Torunn Bruland; post doc NTNU, DMF Gene regulation in biological responses: Focus on gastrin responses in neuroendocrine cells in the gastro-intestinal."— Presentation transcript:

1 Torunn Bruland; post doc NTNU, DMF Gene regulation in biological responses: Focus on gastrin responses in neuroendocrine cells in the gastro-intestinal tract

2 Viral determinants for pathogenesis and the influence of sex on the susceptibility to Friend murine leukaemia virus infection Studies of early retrovirus-host interactions ANIMAL MODEL (mice) virology immunology cell biology signal transduction molecular biology statistic Dr. philos thesis 2003; NTNU, Faculty of Medicine

3 Gene regulation in biological responses

4 Molecular mechanisms in the normal and diseased gastrointestinal system Normal Early gastric cancer Adenocarsinoma

5 Gene regulation in biological responses: Focus on gastrin responses in neuroendocrine cells in the gastro-intestinal tract Introduction Enterochromaffin-like (ECL) cells are a distinctive type of neuroendocrine cells in the gastric mucosa underlying the epithelium Longer term stimulation of ECL cells by gastrin stimulates significant proliferation of ECL cells

6 Several gastrin responsive genes contain cAMP responsive promotor element (CRE )

7 Modulation of gastrin-mediated gene expression by transcriptional regulators of the CREB/CREM/ATF family

8 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 Work plan: cDNA/oligo/splice variant MIKROARRAY

9 Generation of models

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

11 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 statistical methods for: preprocessing and discrimination and classification rule-based methods for classification optimal use of biological background knowledge High throughput 96-well array based Single gene knock-up knock-down (RNAi) animal models Summary

12 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 Gene regulation in biological responses: Focus on gastrin responses in neuroendocrine cells in the gastro-intestinal tract


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