Transcript Gene Expression

Gene Expression
The problem:
Biomedical Engineering is inherently
“reverse engineering” requiring analysisfirst 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 interplay between the genome and the
cell.
The regulatory problem – extragenomic and
gene-driven responses.
Development via differentiation. The unidirectional hypothesis
Signal transduction
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.
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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
– Synthetic systems
The Overall Goal
• Guidance of research.
– The ‘control’ hypothesis
– Mechanistic design of experiments
• Codification of biological knowledge
– Quantification, numerical databases
– Standard mechanisms (computational
modules)
• Synthesis.