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[Challenge Topic] FUTURE OF OPTOGENETICS (Jared Toettcher, Amir Mitchell)

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Posted at 2012-4-30 12:13:33 | All floors |Read mode
Edited by zhiyuanli at 2012-5-10 12:54

original link: http://www.ucsf-pku.org/index.php/FUTURE_OF_OPTOGENETICS

Challenge statement"How can we use spatial and temporal complex inputs to develop a deeper understanding of biology?"
A variety of new techniques are becoming available to the systems biologist for applying inputs that vary in time and space. Optogenetic tools are a powerful collection of techniques for stimulating specific biological activities (e.g. protein binding, ion channel flux, transcription) in a user-defined manner using specific wavelengths of light. But biologists must adapt the way they design experiments and analyze the results in order to use these tools to their full potential. The goal of this challenge is to identify a small number of transformative experiments that will apply variable inputs to probe biological systems in new ways.
Some key topics and areas of interest will be: multicellular communication/computing, system identification in signaling pathways (deducing feedback and feed-forward connections), quantifying signal processing.


Possible or anticipated outcomesWe anticipate developing two to three well-reasoned plans for experimental investigations enabled by optogenetic tools. These plans should include the biological system to be studied, a plan for ‘wiring in’ optogenetic inputs, the set of variable inputs to apply (and the system outputs expected), and finally a quantitative analytical framework to connect and interpret them.


Problem backgroundWith any new technology, the experimentalist must adapt the way they design experiments to maximize the information they can learn. Optogenetics is no different - with the freedom to deliver controllable inputs to specific cells or proteins comes the requirement of a framework for interpreting the results. As these tools reach maturity, we're challenged to identify the problems for which they will be most transformative!
Neural optogenetics has focused on expressing components using tissue-specific promoters, and broadly applying light inputs that are ignored by nearby cells not expressing these components. Single-cell optogenetic experiments have 'plugged into' a few signaling pathways for spatial activation, including G protein activation in yeast and mammalian cells. Finally, we're just beginning to have tools for temporal activation experiments at the transcriptional and post-translational levels.\




Schedule

DAY 1, Part 1: Introduction/tutorial
  • Overview of some breakthroughs, exciting current directions
  • The toolbox: neuronal optogenetics, light-gated dimerization, transcriptional induction, split enzyme reconstitution, etc.

DAY 1, Part 2: Brainstorm for the 'team challenge'
  • Identify a set of exciting directions to sleep on (study, update a wiki with ideas, etc).

DAY 2
  • Develop ideas further
  • Continue discussion
  • Vote on ideas, select small number to pursue (or switch to end of DAY 1)
  • Divide up into 2-3 subgroups to tackle these issues in more detail
  • 'Prototype' solutions: come up with an experimental plan (cell types, constructs, optogenetic tool, perturbations to use, expected results)

POSSIBLE DIRECTION FOR DAY 1We could develop a simple MATLAB GUI for probing a small set of gene network (or signaling pathway) architectures. Students could put in various time-varying inputs to different networks and get a sense for how pathway architecture determines the response...

HW ideas
Online simulation"Experiment" with matlab GUI

Reading listReviews on OptogeneticsA few application papers(list of papers to get students excited about this direction)

Other materialsPotentially useful videosOptogenetics panel discussion: http://mediazone.brighttalk.com/event/ReedElsevier/3d191ef6e2-5932-intro%3Demail
Youtube videos (e.g., http://www.youtube.com/watch?v=I64X7vHSHOE (Nature method of the year, focuses on Neurobiology)

WISH LISTWill MATLAB be available to all students? Could we have access to at least a few machines running MATLAB that we can run our simulation software on? Do students have MATLAB access at home (for a homework assignment using this code)?
Are there any experimental resources that would be worth having? The ability to look at photoswitching yeast?

ISSUES TO STILL ADDRESSWe don't want this to get unfocused. We should have a few potential 'grand ideas' for injecting into discussion so even if students don't generate a focused discussion on their own, we can direct it.



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 Author| Posted at 2012-5-7 22:13:18 | All floors
Something from WIKI:
Optogenetics is the combination of genetic and optical methods to control specific events in targeted cells of living tissue, even within freely moving mammals and other animals, with the temporal precision (millisecond-timescale) needed to keep pace with functioning intact biological systems.
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 Author| Posted at 2012-5-7 22:19:37 | All floors
I'm very interested in how "tunable" this tool is. Can the input & output an analogy relation, rather than the "ON or OFF" relation? If such a tool been developed, it will be a perfect place to do real and precise "parameter scan". I always hope to see my chaos in real system...
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IP  162.105.21.109

Posted at 2012-5-9 21:34:47 | All floors
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Can this technique used to modify the circadian rhythm of organisms? In the represilator, the oscillation period is tunable by varying some parameters; maybe optogenetics can give a simple way to tune  and couple the oscillation.
An interesting idea is about using this technique to make bacteria "showing", like neo light. The lighting pattern can be programmed and shines on a bacteria culture. For example, we can use them to write "PKU-UCSF".
  

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The idea of tuning an oscillator's period is a very good idea - and something we should definitely discuss during the workshop! It would be wonderful to use these tools to tunably control a single pa   Posted at 2012-6-21 08:34

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Posted at 2012-5-11 00:47:01 | All floors
I wondered if we use different wavelengths of light to control the behavior of cells, would we consider the influence of natural light? Trauner's lab have developed a optical switch by allosteric controlling of an ionotropic glutamate receptor, but the experiment can only be done in a dark room...

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This can be a tricky problem. Some systems are more sensitive to this issue than others. For instance, sometimes an optogenetic system requires an extra small molecule that you can add to the medium,   Posted at 2012-6-21 08:36

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Posted at 2012-5-11 04:27:49 | All floors
I wondered if we use different wavelengths of light to control the behavior of cells, would we consi ...
tqli replied at 2012-5-11 00:47



Very interesting topic and what's the different between wavelength and lntensity to the engineered cell? Meanwhile,  I am also wondering the possible values of the techinique in evolutionary and devlopment studies... Is it possible to focus on a single network or a pathway presented in different animal models, and try to figure out how and why the network/pathway evolves? Or maybe minotor the same network/pathway of a single type of cell or organism, e.g., stem cells and yeast, and see how they develope? This piece of news here shows that engineered stem cells still hold their opto-sensitivity during and after muturation in the brain while did not impair their natural activities as a neurons[1].

Then, the problems are how "effective" this method is, consistency and correlation, and whether or not such perfect example of network/pathway could exist...However, I'm looking foward to a deeper understanding of its values when combined with data mining and models, and see how it works.

Cheers!

[1]http://medgadget.com/2011/11/combining-stem-cells-and-optogenetics-holds-promise-for-neurodegenerative-disorders.html

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Posted at 2012-5-11 09:49:20 | All floors
Very interesting topic and what's the different between wavelength and lntensity to the engineere ...
Haoxu replied at 2012-5-11 04:27


“Is it possible to focus on a single network or a pathway presented in different animal models”
you make me remind the photosynthesis pathway and the two photosystem P700 and P680 in plants ...maybe we can change the photosystems, let them absorb different wavelegth and showed different colour from the world...

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IP  162.105.23.162

 Author| Posted at 2012-5-15 22:57:38 | All floors
In today's discussion, seems that many people are interested in this one.
so.... any more specific suggestions?
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IP  162.105.160.123

Posted at 2012-5-16 21:45:29 | All floors
Sounds a little cruel. Need we inject some genes into the body? Is there any photoreceptors in the biological system which we can utilize for optogenetics study?

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Posted at 2012-5-17 10:43:26 | All floors
as we have discussed last sunday, we want to use the photogenetics to do something like:
first, controlling the behavior of myocardial cells. the reference " Allosteric control of an ionotropic glutamate receptor with an optical switch" published in nat. chem. biol. may be helpful.
second, controlling cells' fate. for examle, we can change the cross-link of DNA through light and let cells behave different.
third, if we can affect the  extracellular matrix through light, maybe we can control some behavior of the cells from the point of population.

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Posted at 2012-5-17 10:49:42 | All floors
"Cryptic Bioluminescence in a Midwater Shrimp
JON A. WARNER, MICHAEL I. LATZ, and JAMES F. CASE"
this article pulished last year in science may offer us a good photoreceptor

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IP  162.105.248.40

Posted at 2012-5-23 10:11:53 | All floors
May Optogenetics  combine with photo-crosslinking?

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photo-crosslinking is a useful tool in biology studies, but it is irreversible. we can't use it to control the moleculars in organisms.  Posted at 2012-5-24 09:36

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Posted at 2012-5-24 05:19:56 | All floors
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    cheers! and maybe its a good idea to engineer these receptors for "other" purposes

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Posted at 2012-5-26 18:25:14 | All floors
since we can give a periodic signal through these optogenetics tools(binding or gene expression), one project is that we could tune cell cycle by light
besides, we could also perturb the cell by changing proteins spatially, then the other thing we could do is pulling proteins to the wired position where they can't function well, then we could learn how does the network or pathway function.

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Posted at 2012-5-26 18:27:56 | All floors
also we could make a switch by this tool, then it is also very useful in therapy, such as adjusting the level of the drug, making the drug only function in specific cells or organs.

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Posted at 2012-5-26 18:32:52 | All floors
there are plenty of papers about this field recently, most of them are using into neuropsychiatric disease part, i list papers related with unicellular organism, like yeast in which we could try this system in our lab this summer
2011-Methods Enzymology-Light Contorl of Plasma Membrane Recruitment Using the PHY-PIF System
2011-Nature Method-Light-based feedback for controlling intracellular signaling dynamics
2011-Nature Method-The promise of optogenetics in cell biology -  interrogating molecular circuits in space and time

let's play with this fancy tool !

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Good reference! reward 10 points~  Posted at 2012-5-27 17:44

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IP  125.39.117.42

Posted at 2012-5-26 21:35:01 | All floors
budding yeast has specific budding pattern, usually it buds near the last one since some mark genes localized there; so one specific experiment we may try is pulling the proteins involving in bud site decision to see whether yeast buds on membrane randomly

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Posted at 2012-5-28 13:45:21 | All floors
Maybe we can use optogenetics to make a cell grow as large as a grape...

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Posted at 2012-5-28 13:58:03 | All floors
Maybe we can make a cell emit light and the light can influence another cell (for example let the second cell also emit light), then let the second influence the third by light...by this maybe we can make a Dominoes effect to amplify some cell signals or functions through some mechanism.

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Posted at 2012-5-28 15:31:31 | All floors
good point! this idea could be used in industry to improve the production rate!!

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