The search for an answer

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The search for an answer
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Questions

• The detecitive story
• Find clues and look for questions
• Not all witness tell the truth, not all articles
  are the absoulte truth
• Be critical. Always!

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Your Dr. Watson

• Your colleagues and peers
• Treasure box The Article Database
• For example Medline, PubMed
• Books to brush up on rusty knowledge

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Introduction to database searching PubMed
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Then Go!
Type keywords
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Keyword
Authors
Title Year of publication

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Access
Abstract
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Project Example
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Thermosensation and the search for the cold truth

• The mammalian sensory system is capable of
  detecting and discriminating thermal stimuli over
  a broad temperature spectrum
• From noxious cold (lt8C) to noxious heat (gt25C)
• At present six temperature sensitive transient
  receptor potential (TRP) channels have been
  described that together cover almost the entire
  range of temperatures that mammals are able to
  sense.

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Thermosensation and the search for the cold truth

• A number of labratories have studied cold using
  cultured dorsal root ganglion neurons as in vitro
  model of afferent nerves.
• Two populations of cold sensitive cultured DRG
  can be divided by their sensitivity to menthol.
  (Reid et. al. Nature 2001)
• Those that are activated by cold and sensitive to
  menthol
• TRPM8
• Another population that are activated by cold but
  are insensitive to menthol
• ? TRPA1 (also known as ANKTM1)

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Conflict
Did not observe activation of TRPA1 with cold
temperatures when the channel was heterologously
expressed in HEK293 cells
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Conflicts

• The ability of TRPA1 to respond to cold
  temperatures in vitro is still unresolved
• Story et al Cold and mustard oil activates a
  menthol-insensitive population of dorsal root
  ganglion neurons in culture ?TRPA1
• Jordt et al Did not find neurons that were
  activated by mustard oil and cold but not to
  menthol ?TRPM8

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?
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The question

• Is TRPA1 involved in the thermosensation of cold?
• What does the literature say
• Arguments for and against
• Can we devise molecular tools to study this
  question?