Bacterial Chemotaxis

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Bacterial Chemotaxis

• Dr. Chrisantha Fernando
• Systems Biology Centre
• University of Birmingham, UK
• March 2007

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Thanks to

• Uri Alon. The core of this lecture is based on a
  lecture given by Uri Alon, available at
• http//www.weizmann.ac.il/mcb/UriAlon/
• Actually you can even here him giving the lecture
  in audio. I highly recommend it.

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Rating 18 Neutrophil follows and kills bacteria
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What is Chemotaxis?
Rapid Response
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Cant measure spatial gradients!
Difference in chemical too small to be detected
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Runs and Tumbles
Berg, Brown, 1972
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Due to Clockwise or Anti-Clockwise of Flagella
Motor
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Adaptation of tumbling frequency
EXACT
Well mixed reactor Measure tumbles Add
attractant
Adaptation time
Add attractant
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Exact Adaptation

• The steady state tumbling frequency is
  independent of the attractant concentration.

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Mechanism?
6 proteins control this computation. Adler.
Attractant binds
Receptor/Kinase
1000 receptors
Kentner and Sourjik
30 binding sites for CheY on motor
Cooperativity.
CheY-P increases the prob. that motor turns
clockwise, I.e producing tumbling.
Clockwise/Anti-Clock
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Add attractant
Attractant shuts off kinase CheY gets
de-phosphorylated Tumbles decrease rapidly But
how does adaptation occur, i.e increased tumbling
again?
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Adaptation
Methylation can sensitize the detector This
happens slowly, to an extent determined by two
oppositely acting proteins.
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CheR methylates and sensitizes CheB
de-methylates and desensitizes CheB is activated
by CheY-P, i.e. negative feedback loop.
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• How robust is this circuit to change in protein
  concentration? Uri Alon asked whether it was
  fine tuned or robust.

Behaviour Styles!
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Experiments to alter protein levels in real
bacteria.

• Compute average tumbling frequency of population
  using image processing.
• A variety of individual differences were found
  even in genetically identical organisms
  nervous vs. relaxed.

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Robust feature
Not robust
Not robust
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Why is exact adaptation robust?

• Adaptation time and tumbling frequency is not
  robust.
• Mutants with only partial adaptation (no CheR and
  CheB) have 1 normal chemotaxis ability.
• Hypothesis Chemotaxis mechanism evolved so that
  exact adaptation was robust to variation in
  protein level changes.
• Is it possible to have a good chemotaxis
  mechanism without exact adaptation?

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Protein is noisy

• Sometimes only 20 copies of a protein in a cell.
  This will vary due to noise in transcription and
  translation.
• Imagine making a circuit that had to be robust to
  very unreliable and poorly specified electrical
  parts.

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CheB


Active
Em
Output
E
CheR
Input u
Inactive

• Tar complex (E) in methylated and unmethylated
  form
• Ligand binds to methylated form only, and
  inactivates
• We require a steady fixed active Em.
• So, in proportion to Em active, we destroy Em
• This means, if u is increased, there is less
  Em, so less destruction of Em so, Em again
  increases to its steady state.
• Or, if u is decreased, Em is increased, and
  so Em destruction rate increases so again
  reducing Em to steady state.

Em
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Binds to only Methylated receptors
Chemoattractant
Active receptor
Rate of de-methylation By CheB
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Problems with Current Explanations

• Explaining how the Tar complex can be so
  sensitive (high gain) over many orders of
  magnitude.

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Dennis Bray Outstanding Issues

• http//www.pdn.cam.ac.uk/groups/comp-cell/Question
  s.html