GeneExpression-MedUniWien基因表达-维也纳医科大学.pptVIP

Gene Expression The problem:Biomedical Engineering is inherently “reverse engineering” requiring analysis-first and synthesis second. (A good system has already been built.)Analysis at cell level has been reversed:Traditional: symptom to function to metabolite, to protein (often enzyme) to gene.Now: Gene (genomics) to protein (proteomics), to metabolite, to function. The Need for Quantification Massive amounts of qualitative information Genome (human – 3 109 nucleotides; ~40,000 genes): Introns and Exons Individual genes: promoters, operators, transcribed regions. Transcription Translation Protein processing Gene Networks Transcription factors Inducers, represssors, attenuators, anti-attenuators. The need for quantification. A large signaling network Characterize “devices” Identify “connections” Little spatial segregation Physical systems use channels to direct signals; media are common to many channels Biological systems use highly differentiated chemical complementation. The need for quantification. Complex objective functions Technical approaches Scale I: Bioinformatics Searching the genomic database – The ultimate goal is to link all sequences to their functions. Interspecies: look for highly conserved regions to infer basic behavior. Use functionally identified sequences in one species to infer function in other species. SNP’s Polymorphic mutations Multiple gene diseases Bioinformatics … Intraspecies: Difference between consensus genome and individual genomes. Purpose (disease?) – driven investigation of differences among individuals. Need for clinical database and familial symptomatic and genomic data. Bioinformatics … Pattern-recognition techniques Alon’s “motifs” Technical Approaches Scale III: ‘Reverse’ physiology Disease-related studies Mechanisms (e.g. chemotaxis, apoptosis,specific differentiation steps) Technical Approaches Scale II: Specifics in Search of Generalizations / Generalizations in Search of Specifics Paradigm systems Syn