K. Robison's Comments on the b-galactosidase Chart and Welz's Reply

Date: Mon, 08 May 95 22:14:07 0800
From: Gary Welz 
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Keith,

Thanks for your comments

robison@mito.harvard.edu (Keith Robison) wrote:

>Your flowchart for lacZ expression already presents the danger of 
>being interpreted in a linear fashion.  The "decisions" made by
>lacI (repressor) and CRP are made in parallel.  You probably have
>not made the mistake, but your diagram would suggest that CRP acts
>first and lacI second.


Yes, this is probably a necessary correction.  But discussing these 
things is just part of the process of refining the model.  It wasn't 
obvious to me that these "decisions" are made in parallel - at least not 
parallel until the activator initially signaled that there was no 
glucose present. 

Maybe the chart should look like:

>I think you'll find such diagrams will suffer from such problems
>increasingly as you try to model a significantly complex system.
>Flowcharts are inherently linear beasts, ill-suited for parallel 
>processes, especially biological ones with many non-linearly combined
>inputs.

Yes, these problems will definitely increase. The representation is meant to be suggestive of the large scale structure. Eventually any flow chart will look like a tangled mess, but that still doesn't discourage me from making more charts. At least not until I or someone else comes up with a better representation of these processes. Though this type of representation is crude and inherently flawed, I haven't seen significantly better ones of gene expression processes in textbooks or journal articles.

I know there are diagrams representing interactions, but they usually relate to the physical relationships of the genes, RNA and ribosomes rather than abstract diagrams of processes. I'm trying to get away from the topography - i.e. the physical layout of things - and instead make sense of the relationships between processes.

Diagrams I've seen of interactions haven't really indicated the overall flow of events, that's also part of what I'm trying to get at.

What might be some of the intitial processes on a chart for a whole organism be? Final processes? What's the relationship between different developmental subroutines? Those are some of the questions that I think would benefit from a large scale analysis. I want to step back and try to see the whole elephant - even if my vision is blurred.

You mentioned problems with

>non-linearly combined inputs.

Yeah, that may be tricky, but think about the fuzzy logic chip that controls the processes taking place in expensive Japanese cars.

>Keith Robison
>Harvard University
>Department of Cellular and Developmental Biology
>Department of Genetics / HHMI
>
>robison@mito.harvard.edu 
Gary Welz

Vahe Bedian commented on the flow chart and Robison's comments.

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