Nutrigenomics Bill of fare and genetic code. -Omics. -omics Technologies. Fingerprinting. Transcriptomics
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1 Nutrigenomics Bill of fare and genetic code Regulation der Genexpression durch Nährstoffe Biozentrum Medizinische Biochemie -Omics -omics Technologies Transcriptomics Fingerprinting Foodstuffs Inkubation Zellkultur Isolation RNS Ribonukleinsäure Prozessierung Markierung -Mikroarray Hybridisierung RNS/-
2 Array Technologies RNA hybridized to DNA Probeset Design Data Analysis Pipeline Bioinformatics & systems biology ~74% of all human multi-exon genes are predicted to be alternatively spliced Approach EXPRESSION Transkription mrn Translation PROTEIN Markiert Methods Transkription mrns crns crns Scannen Transkriptomanalyse
3 Affymetrix technology Viabilität Wirkkonzentration Reportergen-Assays (ARE, NFkB) foodstuff? RNA Isolation Reinigung Markierung -Mikroarray gene list MicroArray Novel approach Pooling creates a biological average absolute expression Viabilität Wirkkonzentration Reportergen-Assays (ARE, NFkB) foodstuff Detoxification Glutathion- Metabolism absolute Expression Absolute Expression of Gene x A B C sample pooling Absolute Expression of Gene x expression in pooled sample RNS Isolation Reinigung Markierung -Mikroarray gene list Inflammation Pathway Novel Validation Strategies Nutrient-gene interactions Influence of footstuffs
4 Carbohydrate sensing Regulation of transcription Energy sensing (Amino acids, TOR, Akt-1, FOXO, p53, Sirt-1); Carbohydrates (ChREBP, SREBPs); Fatty acid sensing (during feeding and fasting, PPARs, Fat oxidation, Ketogenesis; Bile salts sensing (Cholesterol), ATP-binding cassette transporter; farnesoid X receptor (FXR); Inflammatory sensing (Redox-Sensing, NF- B, HO-1, IDO, TNF- etc.); Liver sensing (Metabolic stress, Dedox I/II, CYP450); Cell cycle control (ATM), Apoptosis sensing; Angiogenesis sensoring; Immune sensing (innate immunity, defensins); Odorants and Spices sensing (human gut, EC cells); Carbohydrate rich diet Fatty acids sensing ChREBP - Carbohydrate response elements (ChRE) ist in den Promotoren verschiedener Glukose-responsiven Genen identifiziert worden; in der Abwesenheit von Glucose wird der Transkriptionsfaktor ChREBP von der Protein Kinase A phosphoryliert und im Zytoplasma zurück gehalten; steigt der Glukosespiegel wird eine Phosphatase aktiviert (Xylulose-5-P abhängig) ChREBP kann dann in der Zellkern translozieren und dort an ChREs gebunden zahlreiche Gene transaktivieren; Fatty acids sensing Footstuffs & diseases Stimulation of -oxidation Inhibition of lipid synthesis
5 Lipids & inflammation Lipids & inflammation Lipid mediators Lipid mediators TLR4 recognition of fatty acids can induce the production of proinflammatory cytokines Response elements 1 PKC, p38mapk, ERK1/2, JNK 1/2, PI3K/Akt 4 NEMO P IKK / Ser Cys-SH inactive IKK / 2 I B- Cys-S-S-Cys NF B IKK / Footstuffs & adipocytokines Abbau von I B- NF-kB 3 COX-2, inos, TNF- TNF- Entzündungssignalweiterleitung Macrophages & adipocytes Leptin as an energy sensor macrophages and preadipocytes are genetically related
6 Macrophages & adipocytes Footstuffs & oncogens Nature Reviews Immunology 8, 2008, Hotamisligil & Erbay Ras Onkogen Nature Reviews Immunology 8, 2008, Hotamisligil & Erbay Ras-mTOR sensing Mutiertes Ras - ist immer aktiv (z.b ADP-Ribosylierung durch Mikroorganismen) Sugar-packed diet may boost pancreatic cancer risk Pankreaskrebs increased risk by 93 % Pankreaskrebs Transforming growth factor beta exists in three known subtypes. Upregulated in some human cancers (pancreas). Play a crucial role in tissue regeneration and immune systems Dysregulated Ras signaling can ultimately lead to oncogenesis and cancer Loss of tumor suppressor activity p53 Enhanced matrix degeneration and angiogenesis Metastatic cancer
7 Reactive oxygen species Footstuffs & ROS sensing 1 PKC, p38mapk, ERK1/2, JNK 1/2, PI3K/Akt, PERK Antioxidative capacity Ub Ub Ub Cys-S Zn Cys-S Electrophilic attack 2 Phosphorylation P Degradation Cys-S-S-Cys Nrf-2 3 HO-1, IDO, GST Detoxification, DNA-Repair Phase II Genes Risk benefit assesment Clinical trials Personalized medicine SNPs & epigenetics DNA repair i. early genes Inflammation apoptosis Pathway-oriented gene expression
8 Clinical trials Personalized medicine CEL-Files Whole blood analysis after oral consumption gene list -Mikroarray? Expression Functional Biochemistry Pathways pathway analysis Proteinstructure Gene x Geneontology Biosequence Locus Sequencehomology Interaction systems biology Danke für Ihre Zeit
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