ETH Zurich 2006

From 2006.igem.org

Contents 1 Introduction 2 People 2.1 Students 2.2 Supervisors 2.3 Advisors 3 Events & Timeline 4 Project Ideas 4.1 Individual Phenomena 4.2 Oscillator-based Phenomena 4.3 Collaborative Phenomena 5 Development Groups 5.1 Quorum Sensing based (Dominic, Giorgia, Herve) 5.2 Oscillator based (Urs, Christophe, Jonas) 5.3 Generation based (-) 5.4 Other projects (Jonas, Simon, Dominic) 6 Merged Projects 7 Ballot 7.1 Constructor (aka Project X) 7.1.1 Additional Comments: 7.2 Counter (aka The Thing) 7.2.1 Additional Comments: 8 External Information 8.1 Links 8.2 Papers

Introduction

• About us

People

Students

Simon Barkow	Christophe Dessimoz	Zlatko Franjcic
Dominic Frutiger	Robin Künzler	Urs A. Müller
Jonas Nart	Kristian Nolde	Alexander Roth
Tamara Ulrich	Giorgia Valsesia	Herve Vanderschuren

Supervisors

Jörg Stelling

Sven Panke

Eckart Zitzler

Advisors

Uwe Sauer	Martin Fussenegger	Andreas Hierlemann
Kay-Uwe Kirstein	Ruedi Aebersold

Events & Timeline

• Upcoming Talks

• Meetings

• Timeline

Project Ideas

This is the brainstorming section. In this section you will find random ideas and comments without too much consideration of feasability etc. Crazy ideas and wild dreams are welcome!

Individual Phenomena

Designing and tweaking so that the individual behaves in a desired way.

• Buffer Bacteria
• Random Number Generator
• Linear Amplifier

Oscillator-based Phenomena

Some clocking behaviors, such as counters and integrators etc.

• Generation Counter
• Oscillation Counter
• Swiss Watch

Collaborative Phenomena

Some of us have a great interest in some form of emergent phenomena and group dynamics based on simple local rules and external stimulae. Examples would be behaviors like sorting, pattern detections, flocking etc.

• Edge Detection
• Constructor Bacteria
• Sorting Bacteria
• Predator-Prey Behavior
• Pulser

Development Groups

We decided to cluster related projects and to form groups which will dedicate their time to this cluster. The goal is to converge to some single preferred solution based on these project ideas while keeping an eye on feasability, coolness, usefulness, and modular architecture on the way.

If you are in no group yet, please choose one.

Quorum Sensing based (Dominic, Giorgia, Herve)

• Sorting Bacteria
• Pulser
• Constructor Bacteria
• Controlled Cell Division
• Predator-Prey Behavior

Oscillator based (Urs, Christophe, Jonas)

• Generation Counter
• Oscillation Counter
• Swiss Watch

Generation based (-)

• Generation Counter
• Changing Generation Colors

Other projects (Jonas, Simon, Dominic)

• Edge Detection
• Buffer Bacteria

Merged Projects

The two projects below are the outcome of the work of our two remaining development groups. They both have their pros and cons and the discussion continues until at least Monday evening.

• Project X aka "SO-Constructor" by the development group for the Quorum_Sensing_based projects.
• Counter aka "The Thing" by the corresponding development group for Oscillator_based projects.

Ballot

Please everybody make your vote (1 means "forget it" and 10 means "definitely a Nature paper") on the four criteria.

Constructor (aka Project X)

CONSTRUCTOR	Urs	Tamara	Jonas	Zlatko	Giorgia	Simon	Kristian	Herve	Dominic	Alexander	Christophe	Robin
Usefulness	6	4	-	7	-	6	-	-	-	-	-	-
Feasability	4	8	-	6?	-	5	-	-	-	-	-	-
Modularity	10	8	-	10	-	9	-	-	-	-	-	-
Coolness	9	7	-	10	-	9	-	-	-	-	-	-

Additional Comments:

Tamara:
As an engineer, I think the counter is completely useful and totally cool as well. I'm really
excited at the prospect that it might actually work (which I frankly still doubt a little bit at
the moment). The SO-Constructor definitely is cool as well, but I don't see it's usefulness yet,
but as I'm no bilogist, it is not mine to judge.
Talking about modularity, I see that the SO-Constructor has a lot of modules, but they are not
'parallel' modules, but 'serial' modules, i.e. if one module fails, the overlaying modules won't
work as well. They strongly depend on each other. I also see the problem of tuning, because there
is a real lot of tuning to do and nearly everything needs to be tuned. For me, some questions 
arise like: Can you simply change the threshold for a certain protein in quorum sensing? Anyway,
the probability that we have some results to present in the end is still relatively high.
I don't think the counter is really modular, altough it is a combination of one basic part (the
'thing'). The point is, if that basic part works, the whole counter probably works as well. If it
doesn't, then we don't have anything at all. But shouldn't we just take the risk and try it? No
risk, no fun :-)
Conclusion: The SO-Constructor is in my opinion the 'safer' option, meaning that we are much more   
probable to get something that actually works. Whereas the Counter is much more useful and
revolutionary, at least when we get to work it somehow.

Dominic:
As I already have said during the meeting, I am a little bit concerned about the effects of the 
different presentation styles and levels of detail: it is hard to judge the feasability of one or
the other, since for the SO-Constructor I can see a clear stepwise approach with controllable
biological units to implement, but I am doubtful about the tuning and proper interplay of all these
components - although I am confident that to some degree this can be achieved. 
As for the Counter I am also not sure about the basic biological assumptions, e.g. whether the
toggle switch units are available and will work as well as the symmetric repression/activation
that is necessary, although the modeling part suggests everything is straightforward - but this
might be deceiving.
It is hard for me to judge the biological unpredictabilites and risks, but from an engineering
point of view the Counter building block is of the more useful thing to do, since it has a broad 
application range thanks to the clear interfaces. 
Last but not least such a technical unit seems more suitable in the context of Synthetic Biology.

Urs:
I think if the whole thing works this project is astonishing. But I'm in doubt about it. The fact
that you could model each step seperatly is of course a big advantage of this project. The 
probability that at least a few of the steps work is quite high and so you will see some results at 
the end. I'm not so sure about the usefulness. To encapsulate some bacterias which produce a 
certain substance could be usefull but I'm not an expert in this stuff.

Zlatko:
I like the general idea and concept of the SO-Constructor project very much, even if many team members
expressed their doubts about the practical benefits (as Urs mentioned above it could be used for
substance (e.g. drug) encapsulation. I'm not sure, but I think that one may also use the whole thing
for detection and localization purposes (e.g. of toxic substances)). As others pointed out already,
overall feasibility, especially the expected difficulties in connecting the different modules, could
be a drawback here. Dominic, Giorgia and Herve have really elaborated an excellent model, but to me it
seems to be very complex and I don't know if we could manage to set the whole thing up in time (on the
other hand this does not seem to be a general concern because of the "intermediate results"). But
since my knowledge of (applied) molecular biology is very limited and I don't know how (non-)volatile
the counter circuit is, my personal feasibility estimation stands on thin soil.

Counter (aka The Thing)

COUNTER	Urs	Tamara	Jonas	Zlatko	Giorgia	Simon	Kristian	Herve	Dominic	Alexander	Christophe	Robin
Usefulness	10	10	-	9	-	8	-	-	-	-	-	-
Feasability	6	7	-	7?	-	7	-	-	-	-	-	-
Modularity	7	5	-	5	-	8	-	-	-	-	-	-
Coolness	8	10	-	9	-	9	-	-	-	-	-	-

Additional Comments:

Urs:
From the engineer's point of few a counter like this is of course a crucial brick. As you can take 
the concentration of any substance you like (by transforming it to our input S) and also add for 
every single counter step a specific gene needed for an application this counter can be used 
whereever you want. The big disadvantage is of course that if the counter doesn't work there will be
no result you can see.

Christophe:
About feasibility: i don't agree with much of what has been said here. The counter is made of two 
toggle switches. These switches exist in the nature (lambda repressor) and have also been synthetized 
(Gardner et al., partly also on MIT registry). Now, the only things we need to come up with are A) a way 
of having 4 different types of road blocks, which is, as Sven said, possible using zinc-fingers that 
target different dna seqs, and B) a way to have S working as an inducer and as a repressor, in a 
roughly symmetrical manner. And that's all. I am not saying that it is trivial, but seriously, it is 
really doable. And even if we don't manage it to do it for the jamboree, finishing it later could  
still be academically very rewarding.

Bottom line: The difference between the two projects, i guess, is that most of the work in the QS project
would be at the assembling/tuning of existing parts for a very cool final effect, while in the the counter,
we would focus the energy of the whole group into realizing a little module that is reliable and reusable. Both
projects are cool, both teams have done an increadible amount of preparatory work until now and so at this 
point, i would be very excited working on either projects.

Zlatko:
A stable counter would be a very nice thing to have. In my eyes this project seems to be a bit more feasible,
but maybe that's a misjudgement. The model as elaborated by the group is detailed and the simulation seems to
be quite promising. On the other hand the "all-or-nothing" scenario makes it a bit risky.

PS: even though I didn't give a 10 for coolness, I do believe that it's a Nature candidate.

External Information

Links

• Modeling and illustration tools

Papers

bulter04, atkinson03, bates05, keiler01, suetsugu03, sudesh00, römling02, ross91, sutherland01, Lai04, zogaj01, miller01, basu05, goryachev05,

you04,