Gene Expression

1
Gene Expression

• The problemBiomedical Engineering is inherently
  reverse engineering requiring analysis-first
  and synthesis second. (A good system has already
  been built.)Analysis at cell level has been
  reversedTraditional symptom to function to
  metabolite, to protein (often enzyme) to
  gene.Now Gene (genomics) to protein
  (proteomics), to metabolite, to function.

2
The interplay between the genome and the
cell. The regulatory problem extragenomic and
gene-driven responses. Development via
differentiation. The uni-directional
hypothesis Signal transduction
3
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.

4
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.

5
The need for quantification.

• Complex objective functions

6
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.
• SNPs
• Polymorphic mutations
• Multiple gene diseases

7
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.

8
Bioinformatics

• Pattern-recognition techniques
• Alons motifs

9
Technical Approaches

• Scale III Reverse physiology
• Disease-related studies
• Mechanisms (e.g. chemotaxis, apoptosis,specific
  differentiation steps)

10
Technical Approaches

• Scale II Specifics in Search of Generalizations
  / Generalizations in Search of Specifics
• Paradigm systems
• Synthetic systems

11
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.