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[Challenge Topic] BIOCHEMICAL NETWORK DESIGN (Volkan Sevim, Raj Bhatnagar, Illes Farkas)

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Posted at 2012-4-30 12:05:00 | All floors |Read mode
Edited by zhiyuanli at 2012-5-12 19:12

Oringinal Link: http://www.ucsf-pku.org/index.php/BIOCHEMICAL_NETWORK_DESIGN


If you plan to attend this session, then please do the following:
Have a look at [http://www.youtube.com/watch?v=M66ZU2PCIcM this video about team work] at the design company IDEO.
See the  "Homework" section below
Tell us what background you have in (a) Modeling, (b) Stochastic simulations, (c) Programming. <br/>Click to contact us: [mailto:volkan.sevim@ucsf.edu Volkan Sevim], [mailto:raj.bhatnagar@gmail.com Raj Bhatnagar], [http://hal.elte.hu/fij Illes Farkas].

Thank you and see you in 北京.

Challenge statement
Design a circuit that can perform more than one function. Part of the challenge is to quantiatively define "function", "circuit" and "performs a function".

Outline

This plan assumes that (a) four days will be spent on this topic and (b) there will be short presentations after Day 2 and Day 4.

Day 1. Getting on board

*Motivation: With examples. (Volkan, Raj, Illes)
**Are there general principles in biology? Example: FFLs have been found in many different organisms/pathways. Why? Look at 4-5 examples in particular.
**Look at 2-3 examples where one circuit can do more than one thing.
**Brainstorming: Listing and grouping possible functions.

*Functions (Volkan, Raj, Illes)
**How do we define the "functionality" of a circuit?  What criteria are appropriate?
**Review functions that have been previously studied by biologists: Adaptation, switching, oscillators.

*Biochemical network modeling (Volkan)
**Intro based on [http://books.google.com/books?id=roHTk4m8JGAC Wilkinson's book]
**Underlying principles: mass action kinetics, Michaelis Menten kinetics
**Commonly used methods: ODE, boolean, stochastic.  What are the limitations of each approach?  Discuss easy-to-implement variations of these techniques.
**Discussion of BioNetGen based on homeworks

Day 2. Suggesting circuits
*Brainstorming: Listing circuits and testing some of them manually with NFsim. (Raj)
**Reproduce what is already known with some easy examples (Novak-Tyson 2008 may be a good guide)
**how can motifs uncovered?  Discussion of parameter search, topology enumeration, evolutionary algorithms etc

*Prepare evening presentation: How can a circuit perform more than one function? (Volkan, Raj, Illes)
** possible topics: how to design a circuit that responds to different inputs? to the same input but has a different functionality for different parameter sets?
** how to adapt a simple model to include strong biological constraints
** examples in biology of one architecture with multiple functions

Day 3. Selecting circuits
*Scripting intro (Illes)
**Time-consuming analyses are prohibitive without scripting: Matlab, Perl, Python, etc. Based on [http://hal.elte.hu/fij/perl this course].
*Brainstorming: How can we best model our chosen biochemical network? (Volkan, Raj, Illes)
**What is the right granularity to model our network to study the chosen properties?
**What computational analyses can we run overnight?
**Implement simple analysis from pre-compiled parts. Start them in the evening.

Day 4. Producing results
*Compact representation of biochemical network data (Raj)
** characterization of networks using methods from dynamical systems. How can we quantify desirable properties of biochemical networks?
**Phase diagrams
**Stable and unstable states.  Robustness with respect to perturbations of the input or the parameters.
**Possible directions:  Sensitivity analysis.  Probe a circuit with random inputs.
*Evening presentation: Which parameter ranges of which circuits produce more than one behavior? (Volkan, Raj, Illes)

===================================================
THE ALTERNATIVE

Challenge statement
Design a circuit that can generate a switch-like transition by integrating an input signal over a certain period. This signal is simply the concentration of a protein, P, produced by your circuit. You are free to assign any function to the P: it could act as an inhibitor, a transcription factor, or a kinase. Take the amplitude of P is an indicator of the environmental condition: high amplitude = favorable, low amplitude = unfavorable. (XXX How is environment coupled to the production of P? Can we provide P as a timeseries?)

Your circuit should generate a sharp and irreversible transition, e.g., from a low state to high, when the conditions are favorable over a certain period, e.g., 20 minutes. You are free to use any number of components in the circuit. Stick to known biological transcriptional or post-transcriptional regulatory mechanisms.

Day 1
Getting on board. See above.

Day 2
Brainstorming
*Divide an conquer. What are the two functional modules in this circuit? Sensor & switch.
*Design a sensor.
*Design a switch coupled to the sensor.

*Prepare evening presentation:
Describe modules & functions, the roadmap.

Day 3
Demonstrate functionality of the design. Visualization of the output.

Day 4
Compare designs to that of a known biological counterpart, yeast Cln3-Whi5-Cln1/2 circuit. What are the differences? Is there a setting where your circuit can perform better than the yeast's?

Optional: Give your circuits to the bioinformatics group to see if similar designs are seen in real organisms.



==Homework==
'''Reading'''
*Stochastic modeling -- The first subsection (1.1., 2.1, 3.1, etc.) in each section of [http://books.google.com/books?id=roHTk4m8JGAC Wilkinson's book.]
*Dynamics of network motifs -- [http://dx.doi.org/10.1146/annurev.physchem.012809.103457 Tyson-Novak 2010]
*NFsim & BioNetGen -- [http://dx.doi.org/doi:10.1038/nmeth.1546 Sneddon et. al. 2011]
*Design Principles of Biochemical Oscillators -- [http://www.nature.com/nrm/journal/v9/n12/full/nrm2530.html Novak-Tyson 2008]
*Network Motifs -- [http://www.weizmann.ac.il/mcb/Ur ... genetics_review.pdf Alon 2007]
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 Author| Posted at 2012-5-13 08:49:56 | All floors
I'm quite interested in "Design a circuit that can perform more than one function." Some biological circuits in stress response can initiate totally opposite output modules, like the p53 DNA damage response network.
Many work has been devoted to understand how these opposite decisions are made under different stress levels. I think it will be very meaningful and interesting to try to engineer such a system based on one ( or many ) of the proposed mechanisms, and see which one can really complete the task of "life and death decision "
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Posted at 2012-5-15 14:15:29 | All floors
Reply zhiyuanli Add Thread

How to get the book<Stochastic Modelling for Systems Biology>? I can't find the e-book by google link.
I think it is very interesting and fancy to design a circuit for a lot of functions.
But why here is deserted..~~~~(>_<)~~~~
   

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 Author| Posted at 2012-5-15 19:57:34 | All floors
Reply songdaidai Add Thread


    when you try to find something with copyrights, baidu should be better than google~
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Posted at 2012-5-15 22:05:04 | All floors

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Posted at 2012-5-15 22:34:24 | All floors
Reply root Add Thread


    Thank you...~~

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Posted at 2012-5-16 02:36:26 | All floors
I thought a successful network is more or less "a living thing", which constanstly changes and improve itself through various tests, which can cause internal strutural changes, e.g. connections, values, relations, etc. I don't know if neccessary but I think this should be considered to fit the idea maybe as a sub-curcuit into the bigger curcuit that we can have a more flexible model to map real life systems.

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Posted at 2012-5-16 15:07:56 | All floors
Reply Haoxu Add Thread


    Sounds interesting. But I think what you said is an artificial life rather than just a circuit which could perform some functions. As far as I know, designing a complex system which acts as a life is very hard, and I doubt whether we are able to do it in four days...

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Posted at 2012-5-16 16:37:55 | All floors
This topic reminds me of the complex system, which I am very interested in. And this is even more creative, because we are going to design a new complex system. I believe I am suitable for this topic because I am good at modeling as well as programming.

Personally, I like the former one better, because it's more interesting. Besides, the alternative seems to be less complete than the original one.

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 Author| Posted at 2012-5-17 22:36:02 | All floors
Reply skysniper Add Thread

Ya, in silico evolution can easily produce some "computer lifes" that behave like a real one, in the sense that something that can eat, mate, compete, reproduce, mutate and evolve. However, in the wet lab, it is even difficult to define how to "design a life" because most of the things we do is based on certain model organisms. One Interesting relevant work is to design and  synthesize the whole genome of Mycoplasma genitalium
http://stke.sciencemag.org/cgi/content/abstract/sci;319/5867/1215
www.nature.com/nature/journal/v473/n7347/abs/473403a.html



   
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Posted at 2012-5-21 15:35:54 | All floors
Can we really find out some multifunction network in life? By analogy, it is more likely that different functions are assigned to different circuits in a computer, and the multifunction behaviour is achieved by calling different part by a control circuit.

If we want to achieve a multifunction network, maybe it will be at the cost of other properties of the network, such as robustness. So what is the advantage of the multifunction network comparing to a integrated network of different functions module? One advantage might be that the former is easier to build in artifical circuit, because we can use few nodes to achieve more than one functions, and it might be useful under certain circumstance.
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