Comments on: BioBrick as a functional role http://freelancingscience.com/2008/04/03/biobrick-as-a-functional-role/ protein science, open science and freelancing science Sat, 19 Jul 2008 18:40:14 +0000 http://wordpress.org/?v=MU By: Pawel Szczesny http://freelancingscience.com/2008/04/03/biobrick-as-a-functional-role/#comment-366 Pawel Szczesny Sun, 06 Apr 2008 20:09:07 +0000 http://freesci.wordpress.com/?p=95#comment-366 Thanks Raik, but obviously my limited English skills made this post not so easy to understand. I don't recomment just working with proteins. I have seen many protein parts in the Registry and all of them, inluding BBa_I712006, share the same feature - in practice, they are nothing else than pieces of DNA. There's no protein sequence, no functional annotation, no domain breakdown. And to be clear, I don't propose to overlay this DNA sequence with all this information - I want to put this piece into a container that has a function written over it. Such sequence should have all its protein-derived information attached to it, but should be identified by its functional role, not some out-of-nowhere DNA. In this way we can have more than one sequence fullfiling this role - and we should. In the current version of the Registry, two enzymes performing exactly the same function but one normal and one thermostable will be two independent biobricks, with no data shared between. For me it doesn't make sense, as they differ only in stability and sequence - the rest is essentially identical. Both have defined sequence and defined outcome. Why to completely separate them? Plug 'n play receptor concept as you call it is again the same story - instead of having bunch of different biobricks that differ lets say by receptor domain, I want to have buckets with receptor domains, membrane parts, and reporting domains and ability to mix them in novel ways. These combinations if done, should be reported if they work - that's clear. But we don't gain any knowledge if signal transduction component is in the same container with GFP based reporter device. Thanks Raik, but obviously my limited English skills made this post not so easy to understand. I don’t recomment just working with proteins. I have seen many protein parts in the Registry and all of them, inluding BBa_I712006, share the same feature - in practice, they are nothing else than pieces of DNA. There’s no protein sequence, no functional annotation, no domain breakdown. And to be clear, I don’t propose to overlay this DNA sequence with all this information - I want to put this piece into a container that has a function written over it. Such sequence should have all its protein-derived information attached to it, but should be identified by its functional role, not some out-of-nowhere DNA. In this way we can have more than one sequence fullfiling this role - and we should. In the current version of the Registry, two enzymes performing exactly the same function but one normal and one thermostable will be two independent biobricks, with no data shared between. For me it doesn’t make sense, as they differ only in stability and sequence - the rest is essentially identical. Both have defined sequence and defined outcome. Why to completely separate them?
Plug ‘n play receptor concept as you call it is again the same story - instead of having bunch of different biobricks that differ lets say by receptor domain, I want to have buckets with receptor domains, membrane parts, and reporting domains and ability to mix them in novel ways. These combinations if done, should be reported if they work - that’s clear. But we don’t gain any knowledge if signal transduction component is in the same container with GFP based reporter device.

]]> By: Raik http://freelancingscience.com/2008/04/03/biobrick-as-a-functional-role/#comment-365 Raik Sun, 06 Apr 2008 19:35:39 +0000 http://freesci.wordpress.com/?p=95#comment-365 On a first glance, the MIT Registry may seem to only contain "transcription logic" parts but there is, actually, also an increasing number of protein (domain) Biobricks. Your plug 'n play receptor idea,for example, was already put into practice by the 2007 iGem team from Slovenia: See BBa_I712006! Two more teams were working with protein parts during the 2007 iGem. Check out the projects from Freiburg and UCSF! BTW, out of those only 3 protein teams, 2 made it to the final. So working with proteins is a clear winning strategy. Ah, and there are also 2 Riboswitch Biobricks on their way to the registry: e.g. BBa_I752000 You have a good point that we ultimately want to get away from the strict DNA-centric view and this discussion is already in full swing. On the other hand, we absolutely need to have a single exact sequence for each actual Biobrick. We couldn't do any reproducible engineering otherwise. The more abstract information you are describing could then be layered on top of this basic Biobrick description. On a first glance, the MIT Registry may seem to only contain “transcription logic” parts but there is, actually, also an increasing number of protein (domain) Biobricks. Your plug ‘n play receptor idea,for example, was already put into practice by the 2007 iGem team from Slovenia: See BBa_I712006!
Two more teams were working with protein parts during the 2007 iGem. Check out the projects from Freiburg and UCSF! BTW, out of those only 3 protein teams, 2 made it to the final. So working with proteins is a clear winning strategy. Ah, and there are also 2 Riboswitch Biobricks on their way to the registry: e.g. BBa_I752000

You have a good point that we ultimately want to get away from the strict DNA-centric view and this discussion is already in full swing. On the other hand, we absolutely need to have a single exact sequence for each actual Biobrick. We couldn’t do any reproducible engineering otherwise. The more abstract information you are describing could then be layered on top of this basic Biobrick description.

]]> By: Pawel Szczesny http://freelancingscience.com/2008/04/03/biobrick-as-a-functional-role/#comment-362 Pawel Szczesny Sat, 05 Apr 2008 19:47:19 +0000 http://freesci.wordpress.com/?p=95#comment-362 Bryan, if I understood you correctly, your idea for a biobricks is to have a set of sequences, that fullfil a certain functional role, and while this is what I mean here, it's only part of the story. Between a function of some gene, and its DNA sequence there's a whole spectrum of information defining interactions of all its levels (DNA/RNA/protein sequence and structure) with other elements at all their levels. This information should be for example semantically included in the definition of a biobrick, so it is more like multiinput/multioutput device, instead of single input/ouput one. Without addressing in some way the complexity of these elements, we are unlikely to scale up (which mean we wouldn't even enter the roadmap you have written). Bryan, if I understood you correctly, your idea for a biobricks is to have a set of sequences, that fullfil a certain functional role, and while this is what I mean here, it’s only part of the story. Between a function of some gene, and its DNA sequence there’s a whole spectrum of information defining interactions of all its levels (DNA/RNA/protein sequence and structure) with other elements at all their levels. This information should be for example semantically included in the definition of a biobrick, so it is more like multiinput/multioutput device, instead of single input/ouput one. Without addressing in some way the complexity of these elements, we are unlikely to scale up (which mean we wouldn’t even enter the roadmap you have written).

]]> By: Bryan Bishop http://freelancingscience.com/2008/04/03/biobrick-as-a-functional-role/#comment-356 Bryan Bishop Sat, 05 Apr 2008 02:14:44 +0000 http://freesci.wordpress.com/?p=95#comment-356 In a sense, this is what we are doing when we are making transcriptional switches and DNA/RNA logic circuits in vitro in synthetic biology; what you have to do is make sure that the various biomolecules (ribo/deoxyribo) <b>only</b> hybridize where you want them to, where you want their sequences to match up, what to match/not-match, and basically it all looks like a nasty regular expression from a late night of perl programming. Then, you use Seeman code and other stuff relating to nucleic acid physics (or just the RNAinverse server from Vienna) to come up with the complementary strands and to make sure you don't accidentally step on your own toe, which is ironic since we call them toeholds anyway. This sounds close to what you are suggesting: instead of specifying one and only one sequence, write a program that can work within a certain domain and generate alternatives that still match the functional specifications, as wrestled from experimentation, computational simulations via molecular dynamics and DNA physics, or from the literature as the case may be. A few friends and I have started a database for this <i>in general</i> for any sort of project, trying to mimic the success of apt and CPAN over <a href="http://heybryan.org/mediawiki/index.php/Skdb" rel="nofollow">here</a> (in the context of a material science project to make a kinematic self-replicating machine, but this is another subject for another time). - Bryan In a sense, this is what we are doing when we are making transcriptional switches and DNA/RNA logic circuits in vitro in synthetic biology; what you have to do is make sure that the various biomolecules (ribo/deoxyribo) only hybridize where you want them to, where you want their sequences to match up, what to match/not-match, and basically it all looks like a nasty regular expression from a late night of perl programming. Then, you use Seeman code and other stuff relating to nucleic acid physics (or just the RNAinverse server from Vienna) to come up with the complementary strands and to make sure you don’t accidentally step on your own toe, which is ironic since we call them toeholds anyway. This sounds close to what you are suggesting: instead of specifying one and only one sequence, write a program that can work within a certain domain and generate alternatives that still match the functional specifications, as wrestled from experimentation, computational simulations via molecular dynamics and DNA physics, or from the literature as the case may be. A few friends and I have started a database for this in general for any sort of project, trying to mimic the success of apt and CPAN over here (in the context of a material science project to make a kinematic self-replicating machine, but this is another subject for another time).

- Bryan

]]> By: Turulcsirip - attilacsordas http://freelancingscience.com/2008/04/03/biobrick-as-a-functional-role/#comment-355 Turulcsirip - attilacsordas Thu, 03 Apr 2008 18:19:51 +0000 http://freesci.wordpress.com/?p=95#comment-355 [...] I really like your constructive BioBrick criticism: BioBrick as a functional role http://freelancingscience.com/2008/04/03/biobrick-as-a-functional-role/ « előző | attilacsordas — 2008. 04. 03. [...] [...] I really like your constructive BioBrick criticism: BioBrick as a functional role http://freelancingscience.com/2008/04/03/biobrick-as-a-functional-role/ « előző | attilacsordas — 2008. 04. 03. [...]

]]> By: Turulcsirip - attilacsordas http://freelancingscience.com/2008/04/03/biobrick-as-a-functional-role/#comment-354 Turulcsirip - attilacsordas Thu, 03 Apr 2008 18:18:06 +0000 http://freesci.wordpress.com/?p=95#comment-354 [...] I really like your constructive BioBrick critics: BioBrick as a functional role http://freelancingscience.com/2008/04/03/biobrick-as-a-functional-role/ « előző | attilacsordas — 2008. 04. 03. [...] [...] I really like your constructive BioBrick critics: BioBrick as a functional role http://freelancingscience.com/2008/04/03/biobrick-as-a-functional-role/ « előző | attilacsordas — 2008. 04. 03. [...]

]]>