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Tag Archives: Synthetic biology

Synthetic biology is not engineering, it’s a programming

Topic of this post has been sitting in my head for the very long time, but I couldn’t come up with a good enough opening. I’ve found it recently in the comments thread under the post on systems biology by Derek Lowe over at In the Pipeline. Citing Cellbio:

A trick of the human mind has us believe that if we rename something, we have changed the fundamental nature of the beast, but we have not.

I have taken it out of the context, but it applies very well to current situation in synthetic biology. My enormous frustration with this field comes from the fact that most of so-called synthetic biology is nothing else than genetic engineering with more systematic approach. The whole engineering meme has stuck in people’s head and many of them seem to care more about characterization of the system than about understanding how it works.

If we take a bearing from a car and from a bike, both will differ in shape and very likely one couldn’t be replaced by the other. However, their role and mechanism of work is the same, no matter in which machine we put it (this is BTW what I tried to say in my previous post on BioBricks, but judging from the comments I failed). Mainstream synthetic biology doesn’t seem to be interested in understanding how car and bike works – it’s interested in taking both of them apart as fast as possible, puting labels on the parts and pretend that now we understand how they work. And while this approach can be succesful to a certain extent in engineering, biology, especially synthetic biology, is not engineering, it’s rather a programming.

If we look at the particular component of conserved signalling pathway in two different organisms, its sequence most likely will differ. And for some pairs of organisms sequences of this component stop to be freely exchangable: they need to be mutated to fit particular chassis. Repository of information what works where is a great starting point, but it’s about the time to move further. It’s about the time to express biological systems as sets of functional roles and to build a compiler that transforms an abstract description of biological system into sequence understandable by the particular architecture (organism). This is what I think synthetic biology is all about. It’s designing by understanding.

Formalized language of biological processes sounds like a domain of systems biology, but a compiler certainly doesn’t, so such programming framework could use the best of both worlds. Can you imagine “Hello world” equivalent of a living cell? Or how would you debug program in such language? Sounds like lots of fun.

8 Comments

Posted by Pawel Szczesny on November 19, 2008 in bioinformatics, Biological engineering, Synthetic biology

Tags: BioBrick, Genetic engineering, Synthetic biology, Systems biology

Photography is not a hobby. Updated CV and feedback request.

18 Nov

Yesterday I asked over at FriendFeed for the feedback on my early attempt of making visual CV (big thanks to all who commented). Here’s a revised version that hopefully looks much better. The key to read the image above (click to see larger version) is as follows: Y-axis represents time (with dotted line indicating more or less the present moment); areas of interest are along X-axis; color of the phrases indicates my confidence level; font size denotes amount of time I spent on the topic (so in this case I have spent lots of time using perl, but I still don’t feel very confident about it); placement of the phrases denotes which areas of interest particular project/phrase spans; area below the dotted line shows my approximate plans and hopes for the future.

The first version had “Photography” area instead of “Visualization”, but I needed to change that since it was confusing everybody and raised questions why I put a hobby on a professional CV. Photography (or visual arts) is not my hobby. My hobby is choir singing (which I do for over 14 years already, currently singing jazz and gospel). Visualization/Photography is there to indicate that I consider data visualization one of the most important elements of scientific method. What I’m trying to figure out is what kind of presentation can help us in understanding really complex systems, such as human (genetic, to make it easier) diseases. And when we understand them curing is going to be much easier. At least I hope it will.

Anyway, the true reason to post it is to ask my readers for feedback on missing elements of my plans. So far my ideas for the future research projects split into a few paths. First path is to work further on bacterial systems (or subsystems, such as secretion systems etc.). This work would translate later on into something I call Synthetic Biology Framework, which would be a tool helping in designing new biological systems, and maybe later would result in creating a programming language for a cell. My first ideas about the framework were to design engineered bacteria producing some important compounds, maybe drugs, but now I think the cooler use for the framework would be to design bionano machines. The second path is about modelling of human diseases, with important milestone which is analysis of human genome and metagenome (genobiome as I call it) – if the data will be available. Because I don’t think I could do better here than thousands of scientists if I were using the same information, here’s a moment where synthetic biology comes into play again – I hope that I could design nanomachines that would server as quick diagnostic tools or would be reporting the body state in some mostly non-invasive way (aiming at issue of “how is my cholesterol level building up”). The third path is mostly empty and concerns visualization methods. So far I have no clear idea how to build a system that would visually assist in understanding how cells work. I plan to experiment with 3D printing and 3D visualization of biological networks, but I have no clear idea where this will lead me.

So if you have some opinion, comment, idea how to connect some dots, how to jump from one area to another (for example I have no yet idea how to approach pharmacogenomics), or if you think that it doesn’t make sense at all feel free to comment.

3 Comments

Posted by Pawel Szczesny on November 18, 2008 in Career, Research

Tags: CV, Data visualization, FriendFeed, Human genome, Information Visualization, Photography, Resume, Scientific method, Scientific Visualization, Synthetic biology, Visualization

Future of Science on the (ZuiPrezi) map

30 Sep

I’ve just stumbled across map of predictions about global science and innovation created at a recent IFTF workshop in Singapore (the interface is a novel service for online presentation called ZuiPrezi – it looks very promising and I’m waiting for it to come out of private beta). The map contains a few points that resonate with my own scientific interests:

bioelectricity, microbial fuel cells and self-assembly for molecular electronics were for me areas where synthetic biology comes into play
scientific publications changing from journals to articles and proposal to make an institute for free exchange of ideas looked like indications that Science 2.0 memes are spreading very well
and finally, I’m happy to see more people believing that real-time, non-invasive and possibly 3D sensing of biological processes (aka “how is my cholesterol level building up?”) will be available sooner than in 50 years

As usuall with such predictions, I feel like many of them are quite conservative – or even schematic. Only very few were completely new to me, but that’s not necessarily a bad thing. It means that actually most of these predictions will turn out to be true in some time. I would like to see something that would immediately blow me away, but on the other hand it’s all relative :).

Crowdsourcing the future: Can alternate reality game Superstruct help save the world?

1 Comment

Posted by Pawel Szczesny on September 30, 2008 in Comments, Research

Tags: Energy, Institute for the Future, Microbial fuel cell, Synthetic biology, Technology

BioBrick as a functional role

03 Apr

When I initially saw The MIT Registry of Standard Biological Parts, I just fell in love with the idea. However, after closer inspection I realized that it’s not what I hoped to find. The Registry collects an interchangeable functional modules that can be assembled into novel biological systems. And it does it as good as it sounds, but to a certain extent. Pedro wrote some time ago about unavoidable complexity and potential issues with collected parts. I completely agree with his arguments but I have even more doubts about the Registry’s current approach.

First of all, my feeling is that DNA-centric view of life starts to limit us in understanding what is happening at a molecular level. It moved forward science a lot and it is still extremely useful, but with genetics we are not going to understand and avoid emergent properties of biological systems. DNA, RNA, proteins at a sequence and structure level are all interacting with each other. This properties are encoded in DNA, I agree. However, as Pedro pointed out, we have no way to predict what happens after transferring a part to other organism. It is possible to select for mutations that will render this part usable in the other organism, but I don’t think this approach would be of much use if we deal with organisms that are hard to grow (imagine you want to insert a specific system into extremophile organism). And what is more, it’s not necessarily practical if we transfer the part to an organism which already has a similar element encoded in the genome.

In my humble opinion, the Registry can be extended in two directions, transforming parts into a containers that have a specific functional role and include sub-gene elements, like domains or tectons. Let me describe both in more detail.

Currently a BioBrick is assigned a function and a sequence. I would rather see a functional role, that can be fulfilled by many different sequences. For example, if we have an enzymatic function the BioBrick would include not only single DNA sequence from a single organism, but also a protein sequence, domains, sequence motifs and a structure (whatever is available), and all these should be available for all organisms for which we can assign reliably this information. To clarify, I’m far from populating the Registry with BLAST results. I would rather have it done manually, or at least in the way The SEED allows experts to create subsystems and assign a functional roles to proteins. In this way we could just take a gene from a target organism instead of mutating the original one. Having a container would mean that we could include there different flavors of the same gene (for example, after optimization).

For the second thing, I’m a big fan of creating novel functions out of existing elements. That’s a reason why I believe the Registry should include building blocks of proteins as well as other fancy things, like riboswitches. One of the obvious example would be a signal transduction element, where one can attach different receptor domains to the same membrane component. This has been done already thousands of times – why not to standardize it?

Maybe with these two changes maybe we could finally connects some dots and make a complexity of biological systems more understandable or at least traceable. Future directions of the Registry are not very well defined, so I believe there’s a space for at least discussion about such ideas.

7 Comments

Posted by Pawel Szczesny on April 3, 2008 in bioinformatics, Biological engineering, Synthetic biology

Tags: BioBricks, bioengineering, Synthetic biology

Peptide and Protein Building Blocks for Synthetic Biology – EHC Broomley et al.

04 Feb

With my background in protein sequence analysis and recently increasing interest in synthetic biology/biological engineering, Deepak’s post about BioBrick project immediately caught my eye. However, after spending some time around registry of standard biological parts I realized that using full natural proteins as modules wasn’t very appealing to me. My thoughts oscillated in area between nanotechnology at a atomic level, and BioBrick approach – my idea for “a brick” was something from supersecondary structure elements to protein domains.

While I was trying to figure out what was done in this area, here’s what appeared in Google Reader: Peptide and Protein Building Blocks for Synthetic Biology: From Programming Biomolecules to Self-Organized Biomolecular Systems by E.H.C. Broomley, K. Channon, E. Moutevelis and D.N. Woolfson (DOI: http://dx.doi.org/10.1021/cb700249v). It’s not an open access paper, but you can download it from Dek Woolfson lab page. This review summarizes several different approaches to synthetic biology focusing specifically on peptides and proteins as a prime component of newly engineered machines. Why actually peptides and proteins? Here are some points from the paper:

efficient, reproducible and spontaneous folding with all information usually encoded in the polypeptide chain
organization of the folded structures, including secondary structure elements (referred there as tectons), which naturally limits the possible number of folds, but gives enough different structural scaffolds to display many biological functions
frequently observed self-assembly of folded structures into higher-order complexes/nanomachines

The review gives examples of selected protein folding motifs (like collagens or zinc-fingers) that can be used in designing novel fibrous materials, but describes in great detail various assemblies made of protein coiled-coils.

Being pretty familiar with coiled-coil structures, I was rather more interested in general view on the field – and I wasn’t disappointed. Below I copied first figure from this paper (for its legend see the original paper) – it’s a beautiful breakdown of different methodologies in synthetic biology. You can place on this graph most approaches people are taking in this area (from Venter’s bacteria, through BioBricks, to DNA cubes).

Peptide and Protein Building Blocks for Synthetic Biology - EHC Bromley et al.