Interacting gene circuits

1
Interacting gene circuits

• http//occawlonline.pearsoned.com/bookbind/pubbook
  s/bc_mcampbell_genomics_1/medialib/method/mirror/G
  raph/u9sspp.htm
• Discovery questions 27 and 28

2
Protein-DNA interactions

• http//occawlonline.pearsoned.com/bookbind/pubbook
  s/bc_mcampbell_genomics_1/medialib/method/mirror/P
  etri/s_purp_w.htm
• Discovery questions 29-31

3
How do cells throw switches?

• Gene regulation is a stochastic process that must
  differentiate between signal and noise.
• Models for these stochastic processes
• Binomial model
• Normal model

4
Cell division

• 50 copies of a given proteins6 of the time one
  cell will get 19 or fewer copies and 6 of time
  it might get 31 copies
• Binomial frequency function assumes independent
  experiments
• The fate of one molecule is independent of the
  other 49

5
Whither the molecules

• 50 trials, n50
• Each trial results in success with probability of
  p, in this case p0.5 for each cell
• (n/k) pk(1-p)n-k (first feature is binomial
  coefficient)
• Probability that one cell gets 25 molecules
• (50/25) (.5)25 (1-.5)50-25 0.112

6
The effect of stochastic process and noise

• Proteins are expressed in bursts of varying
  durations with different outputs
• The total number of proteins produced from any
  one gene is not the same each time, but an
  average normal distribution

7
Stochastic effects

• Randomness means that if you measure the amount
  of protein produced by the same gene in thousands
  of identical cells the outcome will vary.
• Normal or Gaussian distribution

8
The return of lambda and the repressilator

• Pgs. 236-241

9
Ok, but how does it all work?

• Sports analogy very nice
• Cooperation through communication
• Cell sentries emit signals to organize
• Checkpoints
• DNA replication for example
• Redundancy
• Multiple ways to do anything and everything

10
How reliable is a system?

• Reliability probability of B being produced
  (arbitrarily set at 0.9)
• If B production requires two genes, R .81
• Etc. page 243