Torunn Bruland; post doc NTNU, DMF

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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
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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

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Gene regulation in biological responses
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Molecular mechanisms in the normal and diseased
gastrointestinal system
Normal Early
gastric cancer Adenocarsinoma
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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
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Several gastrin responsive genes contain cAMP
responsive promotor element (CRE)
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Modulation of gastrin-mediated gene expression
by transcriptional regulators of the
CREB/CREM/ATF family
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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

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Generation of models
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Hypothesis testing high throughput/single gene
Reverse Transfection RNAi
Microarray
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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

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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