TMT Thesis Notes: Difference between revisions
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== Signal Design == | == Signal Design == | ||
Figure out a way to measure the coupling between parameters for a given input time-course | |||
* | *Look at the parameter sensitivities over time. I can use the correlation coefficient as a metic for the coupling between parameters. Define the Independence Coefficient as 1 - abs(correlation coeff). This give a measure of the independence of each pair of parameters. | ||
Figure out how to select input-timecourses that will allow for independent estimates of parameters | |||
*Here we need to pick from a number of possible experiments (input time-courses) to select a set of experiments that will allow for the best possible estimation of each parameter. Presumeably we are looking for experiments where two parameters are independent and the sensitivity is high for both parameters (so they can be simultaneously/independently estimated from one experiment), and experiments where the sensitivity is high for only one parameter out of a pair of non-independent (ie correlated) parameters. | |||
* | |||
== Parameter Estimation == | == Parameter Estimation == |
Revision as of 11:54, 6 June 2006
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Biology
- Show that cells can live on a chip
- Stick yeast cells down in the channel, and flow media (at a slow rate) over them. Take a picture every 5 mintutes and compile into a movie of yeast cells growing (hopefully). Need to start with cells growing exponentially, and concentrate to OD 1.5-2. Try sonicating briefly to break up clumps (talk to Jeff).
- I've proven to myself that cells can grow on a chip, though I still don't have a good movie demonstrating this. I will try to get this evidence so everyone will be a believer.
- Show that you can control in ON/OFF fashion response of cells to alpha factor
- Using strain with YFP driven by Pprm1 promoter. Show that cells won't react (ie fluoresce) when they are not in part of channel where alpha factor is flowing, and that they do react when they are exposed to alpha factor. I need to use casein in the media to block pheromone adsorption to the tubes and channel walls.
- Find out if reset of receptor/G protein sub-system is limited by pheromone dissociation or Ste2 internalization.
- Hit cells with a short dose of pheromone and see if reset is on the order of 4-5 mintutes (internalization) or 10 minutes (dissociation). See if Alejandro has already done this.
- (Is yeast pheromone response the best model system for this project?)
Data Collection/Analysis
- Show that you can measure Ste5-YFP translocation to membrane
- This will involve either using or reimplementing the image analysis tools used by Alejandro and Andrew. Also, I might want to use/reimplement their autofocus routine. I should look into this soon.
Signal Design
Figure out a way to measure the coupling between parameters for a given input time-course
- Look at the parameter sensitivities over time. I can use the correlation coefficient as a metic for the coupling between parameters. Define the Independence Coefficient as 1 - abs(correlation coeff). This give a measure of the independence of each pair of parameters.
Figure out how to select input-timecourses that will allow for independent estimates of parameters
- Here we need to pick from a number of possible experiments (input time-courses) to select a set of experiments that will allow for the best possible estimation of each parameter. Presumeably we are looking for experiments where two parameters are independent and the sensitivity is high for both parameters (so they can be simultaneously/independently estimated from one experiment), and experiments where the sensitivity is high for only one parameter out of a pair of non-independent (ie correlated) parameters.
Parameter Estimation
- Get jacobian working
- Would knowledge of parameter groupings affect parameter estimation? I want to think about this some more, maybe chat with some people in the lab, and try to talk to John Tolsma (@Jacobian) about this.
Administrative Issues
Thesis Committee
Q1. Do we need Thorner on the committee?
- I think so.
Q2. Do we need a yeast person on the committee?
- Thorner
Q3. Do we need a dynamic systems person on the committee?
- It's looking more and more like the answer is yes. I don't know enough to be efficient at guiding myself through the parameter estimation and dynamic system analysis. Figuring out who we can add should be a top priority.
- People to talk to:
- Jacob White
- Alan Oppenheim
- He suggested that I talk to George Verghese. Looking at his research interests it looks like he could be the right guy to talk to.
- Paul Barton
Should have a committee meeting ASAP to discuss current directions.
Should have another committee meeting mid/late Spring 2006 to update and plan.
Decision Points/Milestones
Much of my research depends on several programs working correctly (Jacobian, SloppyCell). Since neither of these programs are in their final releases yet (and may still contain bugs), I need to set decision points by which I need to have complete confidence in the program. If the program is not working by this decision point, then I will find a new program/method.