[BBF Standards] systemic limitation of biobricks for combinatorial logic?

[Drew Endy]

As background information relevant to your discussion:

1. there is a common signal carrier for gene expression devices.  it  
is called PoPS, for Polymerase Per Second.  read about it here: http://openwetware.org/wiki/Adventures

2. biochemical cross talk within a self mixing volume can be handled  
via the specificity of molecular interactions.  look up zinc finger  
DNA binding proteins.  read Reshma Shetty's dissertation from MIT  
(this year).  Also read Zarrinpar A, Park SH, Lim WA., PMID: 14668868

3. new organelles could be created thereby providing engineered  
additional spatial insulation.  see the 2007 UCSF iGEM team's second  
project (here: http://parts.mit.edu/igem07/index.php/UCSF/Organelle_Intro) 
.  Also read Barry Canton's dissertation from MIT (this year).

4. cell-cell signaling can be used to communicate across bacteria.   
read Weiss and Knight (http://www.princeton.edu/~rweiss/papers/rweiss-dna6.pdf 
) and more recent papers from Ron's lab at Princeton (see http://weisswebserver.ee.princeton.edu/pubs.html) 
.

Drew



On May 19, 2008, at 10:42 PM, James Lawson wrote:

> Hi folks,
>
> This might be a little from left field, and I don't have the  
> solution, but I have had this idea since I became familiar with the  
> gene-centric abstraction level that the entire Biobricks / standard  
> parts systems is based on. I don't think the level that we're  
> designing these systems at is helping us here, particularly with  
> respect to this system-wide visibility of gate outputs. We have no  
> 'encapsulation' mechanism. The non-nucleated cells we're using as  
> chassis for these systems don't have any mechanism for membrane- 
> based compartmentalisation, so any all the 'computation' is done in  
> pretty much the same compartment. Nucleated, compartmentalised cells  
> are able to get a step further by creating an encapsulation  
> mechanism, where some kind of reaction or transformation of species  
> may be contained within a delineated zone.
>
> Leveraging any of these membrane compartmentalisation (or membrane  
> mircodomain) based systems of encapsulation would require some  
> pretty extensive engineering and standardisation of the transport  
> and cytoskeletal systems within a cell, so I guess it isn't really  
> tractable for a while.
>
> To add to Herbert's comments:
> In unicellular organisms, one could say that quorum sensing systems  
> are analogous to neural networks in multicellular organisms as a  
> solution to this problem of encapsulation and input/output  
> visibility management we're talking about. I have heard quite a lot  
> about people doing engineering with quorum sensing systems and I  
> think this is probably where the synthetic biology community will  
> continue to look to. I don't really know how much we know about  
> heterogeneous bacterial colonies - perhaps someone could enlighten  
> me on the state of the field?
>
> Kind regards,
> James Lawson
>
> Herbert Sauro wrote:
>> Funny you should mention this solution:
>>
>> > Can this be solved by using single cells for each circuit, then
>> > somehow providing inter-cell communication?
>> > (Also seems quite difficult, correct?)
>>
>> Because this is how evolution got round the problem by inventing  
>> neural circuits.
>>
>> Herbert Sauro
>>
>> J C wrote:
>>
>>> Hi all,
>>> I have been reading about biobricks for some time,
>>> I am a computer engineer.
>>>
>>> For combinatorial logic, it seems the limitation of biobricks
>>> is the system-wide visibility of all gate outputs, is this correct?
>>> In circuits with multiple gates, each gate must employ a unique
>>> input signal and output signal, otherwise the multiple outputs
>>> will conflict with the inputs.
>>>
>>> How is this being addressed other than by finding unique
>>> signals to feed to each gate?
>>>
>>> This is not a scalable solution for larger circuits, i.e. adders
>>> or latches (RAM storage for more than 1 bit).
>>>
>>> Can this be solved by using single cells for each circuit, then
>>> somehow providing inter-cell communication?
>>> (Also seems quite difficult, correct?)
>>>
>>> There was a similar comment on this recently, though I didn't
>>> see any solution discussion?
>>> http://biobricks.org/pipermail/standards_biobricks.org/2008-February/000034.html
>>> "The lack of physical separation of signals, as is the case in
>>> microelectronics, could be one of the biggest limitations to the
>>> standardized bioparts concept. "
>>>
>>>
>>> The idea offered in that thread,
>>> "Actually this could lead to a design process where you operate  
>>> e.g. on a
>>> system level and design your nice circuit, but depending on the  
>>> circuit the
>>> design computer programme chooses one of different devices (and  
>>> finally
>>> parts) that interact in the way you like."
>>>
>>> This is actually quite impossible for multi-gate designs.  A multi- 
>>> bit adder
>>> or memory storage would require far too much complexity.  The  
>>> components
>>> (i.e. "transistors") need to have completely compatible outputs so  
>>> that
>>> any output can connect to any input.  Otherwise they are not  
>>> "generic parts".
>>> Similar issues led to much complexity in the early days of  
>>> semiconductor
>>> fab.
>>>
>>> --
>>> Cheers!
>>>
>>> _______________________________________________
>>> Standards mailing list
>>> Standards at biobricks.org
>>> http://biobricks.org/mailman/listinfo/standards_biobricks.org
>>>
>>
>>
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>
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