Oscillator

Oscillator is Moving!

Thu, 07 Jan 2010 18:00:35 -0500

I’m super excited to be moving Oscillator over to ScienceBlogs! Make sure to update your bookmarks and visit me over at http://scienceblogs.com/oscillator!

"Synthetic" Biology and Evolution by Symbiosis

Sun, 03 Jan 2010 18:42:37 -0500

I like using synthetic to mean “working together”, in “real” synthetic biology as bringing together (synthesizing) a lot of components from different living things in order to create a unique whole, and in “natural” biology in terms of how every living thing must live together with others in communities made up of complex interdependent relationships. I’ve recently been reading a lot of Lynn Margulis’s work on Serial Endosymbiotic Theory (SET): how eukaryotic cells developed through multiple endosymbiotic events between different species of bacteria, with early cooperative relationships leading to intricate co-dependence and entire new domains of life. I love this picture from her article “Serial endosymbiotic theory and composite individuality” for its complexity and for highlighting how deeply connected all life on earth is. We are all synthetic communities.

Synthetic Sources of Natural Rubber

Sat, 02 Jan 2010 12:09:36 -0500

Rubber can be made chemically from fossil fuels, but natural rubber from tropical trees is still the best source, and in many cases the only usable one (car tires need a lot of natural rubber for the right combination of strength and elasticity). Besides being difficult to grow and relatively inefficient, rubber trees are also facing a fungal plague that could potentially wipe out natural rubber within the next few years. Many labs (including mine) are trying to find or engineer different sources of biological polymers. According to a neat article in The Economist, two groups are working with dandelions as potential a new source of natural rubber. One group is using RNA interference to knock down the expression of a gene that makes the rubber polymers that the plant already makes difficult to process, and the other is using more traditional breeding technologies to improve rubber production, selecting and crossing high producers. Not only do dandelions already produce significant amounts already, but their fast growth and ability to grow just about anywhere (which makes them such good weeds) may make them a valuable agricultural commodity.

It’s an interesting project in many ways. Biological polymers are a fascinating and very broad subject, and understanding and engineering how enzymes make and break down these polymers will undoubtably be important for industrial biological engineering. Moreover, a sustainable biological method for producing rubber locally (instead of the current synthetic methods) will be important for environmental conservation and decreasing oil dependence.

However, this also means that there will be serious competition for rubber tree farmers, with likely many negative effects for the economies of Malaysia, Thailand, and Indonesia, the world’s top rubber producers. This has already happened, when the first round of synthetic—but not as good—rubber entered the market, as well as when indigo dyes began to be chemically synthesized, irreparably damaging the Indian dye economy. These and other issues are discussed in an interesting article by Political Scientists working at MIT, “Aspects of the political economy of development and synthetic biology” from a special issue of Systems and Synthetic Biology. These are important but often neglected aspects of the discussion of the risks and benefits of the potential applications of synthetic biology.

Jonah Lehrer on Failure

Fri, 01 Jan 2010 12:07:28 -0500

A great article about failure and science by Jonah Lehrer in Wired, Accept Defeat: The Neuroscience of Screwing Up. I will quote the part about the work of Kevin Dunbar studying how scientists work in their “natural environment” at length because it is awesome:

Science is a deeply frustrating pursuit. Although the researchers were mostly using established techniques, more than 50 percent of their data was unexpected. (In some labs, the figure exceeded 75 percent.) “The scientists had these elaborate theories about what was supposed to happen,” Dunbar says. “But the results kept contradicting their theories. It wasn’t uncommon for someone to spend a month on a project and then just discard all their data because the data didn’t make sense.” Perhaps they hoped to see a specific protein but it wasn’t there. Or maybe their DNA sample showed the presence of an aberrant gene. The details always changed, but the story remained the same: The scientists were looking for X, but they found Y…

The experiment would then be carefully repeated. Sometimes, the weird blip would disappear, in which case the problem was solved. But the weirdness usually remained, an anomaly that wouldn’t go away.

This is when things get interesting. According to Dunbar, even after scientists had generated their “error” multiple times — it was a consistent inconsistency — they might fail to follow it up. “Given the amount of unexpected data in science, it’s just not feasible to pursue everything,” Dunbar says. “People have to pick and choose what’s interesting and what’s not, but they often choose badly.” And so the result was tossed aside, filed in a quickly forgotten notebook. The scientists had discovered a new fact, but they called it a failure.

The reason we’re so resistant to anomalous information — the real reason researchers automatically assume that every unexpected result is a stupid mistake — is rooted in the way the human brain works. Over the past few decades, psychologists have dismantled the myth of objectivity. The fact is, we carefully edit our reality, searching for evidence that confirms what we already believe. Although we pretend we’re empiricists — our views dictated by nothing but the facts — we’re actually blinkered, especially when it comes to information that contradicts our theories. The problem with science, then, isn’t that most experiments fail — it’s that most failures are ignored.

2009 Year in Review

Thu, 31 Dec 2009 11:26:00 -0500

2009 was a big year for synthetic biology in the academic press. Several journals had special issues devoted entirely to the topic, most recently Nature Biotechnology, but also Molecular BioSystems, The Journal of the Royal Society Interface, Systems and Synthetic Biology, and EMBO Reports with excellent research articles, reviews, and fascinating commentaries on economic, ethical, and social issues in synthetic biology. Beyond that Google Scholar returns over 1,000 results for “synthetic biology” in 2009, most of which I unfortunately have not had the chance to read. Of the few hundred where I at least read the abstract I have collected my favorites, the TOP 12 PAPERS IN (broadly defined) SYNTHETIC BIOLOGY OF 2009 (according to one grad student)!!! They’re numbered for convenience more than anything, I couldn’t possibly rank them more specifically, deciding on this few was hard enough. If you have favorites that I missed, please add them in the comments!

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1.) A tunable synthetic mammalian oscillator, Tigges et. al. Nature, 457, 309-312.

You maybe could tell that I am partial to oscillators, the darling of synthetic biology circuits. Oscillators are cool because they are hard to make, have a clear analog in electrical engineering, are important in many natural biological systems (for a really cool article about circadian rhythms and you, check out Olivia Judson’s New York Times blog post), and could be used as a component for future synthetic systems where timing is important. This paper from Martin Fussenegger’s group is the first robust, tunable synthetic oscillator in mammalian cells; that is, individual cells will glow on and off for many cycles with a time period that can be changed by the experimenter. It’s a big step in terms of oscillator design, and future work will further improve the oscillations and allow for synchronized behavior between populations of cells.

2.) A synthetic mammalian electro-genetic transcription circuit, Weber et. al. Nucleic Acids Research, 37(4) e33.

Another paper from the Fussenegger group, this one is interesting because it brings a new input system to mammalian cell engineering: electricity. It’s not a direct electrical input, as with voltage gated channels (which I think would be cooler, but also requires using specific cell types), but uses the indirect electrochemical breakdown of ethanol to acetaldehyde to activate a synthetic gene network through a promoter that responds to acetaldehyde.

3.) Programming cells by multiplex genome engineering and accelerated evolution, Wang et. al. Nature, 460, 894-898.

Optimization of synthetic (or natural) metabolic pathways for the highest possible production of a desired product can be tedious and extremely time-comsuming work. Researchers from the Church lab at Harvard created a robot that would automatically perform cycles of mutating E. coli genomes and then selecting for cells that produce more lycopene (an important industrial chemical). In a matter of hours they were able to test billions of variations and come up with an optimized pathway that makes more lycopene than the natural system and synthetic pathways that have been more laboriously engineered. This Multiplex Automated Genome Engineering (MAGE) method has the potential to make the dream of fast, easy biological engineering a reality by automating directed evolution on a genome scale.

4.) Synthesis of methyl halides from biomass using engineered microbes, Bayer et. al. JACS, 131(18), 6508-6515.

Synthetic biology blurs the lines between species, treating natural ecosystems as bags of genes to be mined and annotated, searched and modeled, synthesized and networked. It’s hard to tell from the sequence alone though how good an enzyme from a certain species will work in your chassis, how it will cooperate with the other components in your pathway, whether it will even function at all. This paper from the Voigt lab deals with just that problem with brute force testing of ninety variants of a single enzyme, collated from genomic datasets and synthesized chemically for expression in E. coli. It’s incredible for the scope and scale, for the output—very high levels of methyl halides, precursors of many important chemicals including fuels—and for the work towards improving our understanding of enzyme function vs. sequence (and the idea that it’s going to take a lot more than bioinformatics alone to get the job done).

5.) Synthetic protein scaffolds provide modular control over metabolic flux, Dueber et. al., Nature Biotechnology, 27, 753-759.

Chemical engineers think of industrial production of chemicals in terms of pipes and vats, and genetic engineers use the language of chemical engineering in analogy: cells as “vats”, pathways as “pipelines,” with chemical intermediates passed between different enzymes that perform different chemical processes in the transition from input metabolites to useful chemicals. This paper from the Keasling lab uses a synthetic scaffold protein to capture and link together the enzymes of a particular pathway to make a more literal pipeline, drastically improving the function of the pathway be preventing “leaks” of the intermediate chemicals that are harmful to the cell. The scaffold protein itself is interesting because it is made up of proteins that control signal transduction in human cells, creating an entirely parallel system in bacteria that will not interfere with signaling or metabolism of the chassis cell. Not only that, it’s been useful for my research (maybe one of the big papers of 2010!)

6.) A synthetic genetic edge detection program, Tabor et. al. Cell, 137(7), 1272-1281.

The “bacterial camera” made with a synthetic light-sensing pathway has been around since 2005, with bacteria that turn black in response to red light, essentially
“printing” an image onto a petri dish covered in the cells. This paper improves on the old design with the addition of many new abstractable transcriptional logic components. Instead of every cell that experiences the light turning color, the bacteria only activate color production when they experience something different from their neighbors, so that only the edges of the lit-up area turn dark. It’s a neat little system, and represents a very sophisticated and compex synthetic network made up of many components.

7.) Spatiotemporal control of cell signalling using a light-switchable protein interaction, Levskaya et. al. Nature, 461, 997-1001.

Light can also be used to activate synthetic pathways in mammalian cells (!!!). This paper is great, it introduces a totally new way of interacting with mammalian cells and it introduces a new functional “part” for synthetic biology, controlling the cytoskeleton to directly alter the shape of the cell. Awesome!

8.) Systems-level engineering of nonfermentative metabolism in yeast, Kennedy et. al. Genetics, 183(1), 385-97

This one is a little biased (it’s from my lab), but it’s a neat paper that uses metabolic modeling in order to find non-intuitive gene deletions that would increase metabolic flux through the formate production pathways in yeast (formate is an industrial commodity and is can be efficiently converted to hydrogen gas by E. coli). The modeling is called flux balance analysis, which uses only steady state information about metabolism in order to find optimum “solutions” to how the cell allocates resources. It’s an interesting way to solve the problem of first of all collecting all the data and second of all having enough computational power to actually model metabolism as the dynamic system that it is, and it can be used for rapidly generating interesting hypotheses and designs for metabolic engineering.

9.) Snowdrift game dynamics and facultative cheating in yeast, Gore et. al. Nature, 459, 253-256.

This is one of my new favorite things—evolutionary dynamics of symbiosis using synthetic “ecosystems” of several species of microorganisms that “cooperate” or “cheat” by using the environment’s resources without giving other cells anything in return. It’s a fascinating look at how cooperation may be more “natural” than we think, and that evolution and natural selection don’t have to be just about bloody and selfish competition for survival. Expect a lot more about this from me in 2010!

10.) Measuring the activity of BioBrick promoters using an in vivo reference standard, Kelly et. al. Journal of Biological Engineering, 3(1).

It’s hard to believe that this paper only came out in 2009, because this kind of foundational work on characterizing BioBrick parts is so critically important for the engineering of biological systems. Almost every project in synthetic biology involves an extended period of optimization, and kinetic components such as promoter strengths are a main focus of such efforts. With a standardized, reproducible method for comparing different promoters, it will be much easier to choose parts “off the shelf” for future synthetic biology project. There is a lot more work to be done, and it will need a lot more papers (or specification sheets?) like this.

11.) Solving a Hamiltonian Path Problem with a bacterial computer, Baumgardner et. al., Journal of Biological Engineering, 3(11).

This paper comes from the 2007 Davidson-Missouri Western iGEM project, where the students used engineered genetic systems in bacteria to solve an NP complete problem. Cool!

12.) How to choose a good scientific problem, Uri Alon, Molecular Cell, 35(6), 726-728.

To round out the list, the least synthetic biology paper, but a thought-provoking, important, and wonderfully touchy-feely look at nurturing good scientists as a mentor and good advice for students for choosing interesting and important problems to study and how to go with the flow when things inevitably don’t work as planned.

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That was 2009, here’s to a happy, healthy, intellectually stimulating 2010!

The Top 100 Science Lecture Videos

Wed, 23 Dec 2009 10:07:40 -0500

The Top 100 Science Lecture Videos :

For people with lots of time on their hands, or a relaxing winter vacation coming up, the top 100 Science Lecture Videos from News Junkie Post, including Richard Dawkins, Kary Mullis, Steven Chu, Craig Venter, Stephen Hawking, E.O. Wilson, and a whole lot of other good stuff!

“The walls between art and engineering exist only in our...

Tue, 22 Dec 2009 09:52:43 -0500

“The walls between art and engineering exist only in our minds.”

-Theo Jansen—Kinetic Sculptor

CURB is fabulous design/marketing firm that uses only natural...

Thu, 17 Dec 2009 16:48:43 -0500

CURB is fabulous design/marketing firm that uses only natural media like dirt, snow, sand, water, and now, “Discofungi”, glow in the dark bacteria that they’ve used to make their holiday greeting cards. Let it glow!

(via notcot)

FlowingData presents the 5 Best Data Visualization Projects of...

Wed, 16 Dec 2009 14:32:56 -0500

FlowingData presents the 5 Best Data Visualization Projects of the Year; according to the article 2009 ”was a huge year for data. There’s no denying it. Data is about to explode.”

Of all the great data visualization, the top pick was Ben Fry’s awesome “On the Origin of Species: The Preservation of Favoured Traces”, which shows the evolution of Darwin’s book as he edited and released different editions. It’s an interesting look into the process of scientific work from 150 years ago that still resonates now in the face of controversies over scientific consensus in climate change research. Science evolves, theories change in response to new data, interpretations of data change in response to new ideas (and new ways to use and visualize the data). Darwin’s ideas have significantly changed the way that people do biology, but the details are hardly set in stone, even during his own career. Overall, lovely, informative, and thought provoking—great data visualization!

via SEED

Bionic robot penguins that can swim underwater or float in the...

Wed, 16 Dec 2009 13:03:13 -0500

Bionic robot penguins that can swim underwater or float in the air! Incredible!

SCIENCE SCOUTS » The “that’s right people, I’m an artist,...

Fri, 11 Dec 2009 18:04:33 -0500

SCIENCE SCOUTS » The “that’s right people, I’m an artist, but I do science-y art and it’s cool” badge.

What's in a name?

Fri, 11 Dec 2009 16:51:39 -0500

Synthetic biology has been used to describe many scientific activities for the past hundred years, and is still far from a concrete definition. Nature biotechnology asked 20 experts in the field how they define synthetic biology, leading to a great article that highlights many of the different pursuits of synthetic biology researchers as well as the common emphasis on engineering principles. Kristala Prather sums it up nicely in her response: “If you ask five people to define synthetic biology, you will get six answers.”

"If biological engineering were aviation, it would be at the birdman stage: some observation and some..."

Thu, 10 Dec 2009 13:43:00 -0500

“If biological engineering were aviation, it would be at the birdman stage: some observation and some understanding, but largely naive mimicry. For the field to really take flight, it needs the machinery of synthetic biology.”

- Unbottling the genes, editorial from a special issue of Nature Biotechnology on synthetic biology

juliasegal: antiheroe: (via ihatesilkepil) What if design is...

Wed, 09 Dec 2009 09:39:06 -0500

juliasegal:

antiheroe:

(via ihatesilkepil)

What if design is hard too?

(via freshphotons via brouillon)

Mon, 07 Dec 2009 15:13:48 -0500

(via freshphotons via brouillon)

Evolution, ecology and the engineered organism

Fri, 04 Dec 2009 10:42:27 -0500

Synthetic biology is fascinating and scary because of evolution. Evolution leads to the incredible diversity of biological systems that synthetic biology can draw from to create new designs, and evolution can be used in the lab to optimize synthetic biology pathways and make them better. However, because cells evolve and interact with the environment, synthetic biology is scary—what will happen when synthetic cells evolve and change in “real” ecological environments? Most synthetic biologists agree that evolution will likely make synthetic cells unfit to survive in the wild, and that evolution is something that synthetic biology systems need to be insulated from in order to maintain proper behavior (given the chance, most living cells would get rid of whatever synthetic pathway they were forced to make, since it would likely compete with the cell for natural resources). A new opinion article by Jeffrey Skerker, Julius Lucks and Adam Arkin, Evolution, ecology and the engineered organism: lessons for synthetic biology in the most recent issue of Genome Biology goes into a lot of these issues; how evolution is both useful and dangerous for synthetic biology, and how to minimize the disruption of natural ecologies as synthetic biology moves forward.

Here’s figure 1 from the article, which I think accurately reflects how everything is connected and how vague our understanding is about these connections and how little we know about what will happen in the future of synthetic biology:

Figure 1 Ecological forces drive evolution, which in turn influences ecologies. This cycle creates a diverse array of functions that can be used in synthetic designs. Individual functions may be combined and evolved in the laboratory to create new synthetic systems that may ultimately enter natural ecologies.

Cribsheet for Synthetic Biology

Thu, 03 Dec 2009 09:25:03 -0500

SEED magazine is one of my favorite resources for science news. They always have great articles, interesting perspectives, beautiful design, and useful content. Each issue has really fun pull-outable “cribsheets” about different trendy science topics, now available online as “downloadable tool[s] for living in the 21st century.” I’ve had the synthetic biology cribsheet up on my desk’s bulletin board for a while (right under the ad for hydrogen fuel cell SUVs featuring Fergie), but I just found it online and wanted to share it (you can download it here).

"Are these microchips really behaving like neurons? Or has the simulation taken a shortcut, and..."

Wed, 02 Dec 2009 10:14:51 -0500

“Are these microchips really behaving like neurons? Or has the simulation taken a shortcut, and turned our neurons into dumb little microchips? Because we sometimes forget that the “mind is like a computer” metaphor is only a metaphor. The mind is really just a piece of meat.”

- Reverse-Engineering : The Frontal Cortex

"As president, I believe that robotics can inspire young people to pursue science and engineering...."

Mon, 30 Nov 2009 12:50:35 -0500

“As president, I believe that robotics can inspire young people to pursue science and engineering. And I also want to keep an eye on those robots in case they try anything.”

- Barack Obama

Algae Batteries!

Sun, 29 Nov 2009 12:49:33 -0500

Algae Batteries!:

Cellulose is an amazingly versatile molecule, it helps plants and algae store energy, it feeds animals of all shapes and sizes, it’s the main ingredient in paper, it’s being used to make biofuels, and apparently it can also hold an electrical charge, essentially making a tiny, flexible, biodegradable battery. Different plants and species of algae have cellulose with different properties that are optimal for different uses, and apparently one of the species of algae that is most damaging in algal blooms, Cladophora, also has the cellulose with the best battery-like properties.

Biological electricity is something that is being heavily explored right now. Some organisms are naturally able to produce electricity (like electric eels and at much lower voltage, many species of bacteria). The idea of using biological materials that don’t have an electrical function in their natural context in batteries or other electronics is fascinating and opens up a whole set of possibilities for biomaterials that I had never really considered before. Perhaps with some more engineering, environmentally-friendly biological batteries (and who knows what else) could be a reality!

(via Seed, via LiveScience)