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. Studies of early retrovirus-host interactions. Viral determinants for pathogenesis - PowerPoint PPT PresentationTRANSCRIPT
Torunn Bruland; post doc NTNU, DMF
Gene regulation in biological responses:Focus on gastrin responses in neuroendocrine cells in the gastro-intestinal tract
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
BIOMEDICAL PROBLEM
SCREENINGgenome-widesystem-wide
HYPOTHESIS GENERATIONdata analysis
HYPOTHESIS TESTING
high throughput/single gene
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
IntroductionEnterochromaffin-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
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
BIOMEDICAL PROBLEM
SCREENINGgenome-widesystem-wide
HYPOTHESIS GENERATIONdata analysis
HYPOTHESIS TESTING
high throughput/single gene
•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
Generation of models
BIOMEDICAL PROBLEM
SCREENINGgenome-widesystem-wide
HYPOTHESIS GENERATIONdata analysis
HYPOTHESIS TESTING
high throughput/single gene
•gastric carsinoma•gastric carcinoids•hypergastrinemia
•gastrin-mediated gene expression•CREB/CREM/ATF-modulated gene expression
•Genome-wide gene expression
•gastric mucosa custommicroarrays
•system-wide screening ofCREB/CREM/ATF splice variants
statistical methods for: •preprocessing and discrimination and classification•rule-based methods for classification•optimal use of biological background knowledge
Hypothesis testing: high throughput/single gene
Reverse Transfection RNAi + Microarray
BIOMEDICAL PROBLEM
SCREENINGgenome-widesystem-wide
HYPOTHESIS GENERATIONdata analysis
HYPOTHESIS TESTING
high throughput/single gene
•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
BIOMEDICAL PROBLEM
SCREENINGgenome-widesystem-wide
HYPOTHESIS GENERATIONdata analysis
HYPOTHESIS TESTING
high throughput/single gene
Prosjektansvarlig Astrid Lægreid, professor, dr.scient.,
ProsjektmedarbeidereLiv Thommesen, førsteam.. dr.philos., HiSTTorunn Bruland, post.doc. dr.philos., IKM, NTNUOla Ween, post.doc. dr.scient., IKM, NFRKristine Misund, cand.scient. NTNUTonje Strømmen, siv.ing. NTNU
Gene regulation in biological responses:Focus on gastrin responses in neuroendocrine cells in the gastro-intestinal tract