PLoS Biology – Darwinian Evolution on a Chip

For evolution afficionados, there is a cool new paper in PLoS Biology on using a microfluidic chip to conduct in vitro evolution experiments.

The paper, by Brian Paegel and Gerry Joyce from the Scripps Research Institute

relies on computer control and microfluidic chip technology to automate the directed evolution of functional molecules, subject to precisely defined parameters. We used a population of billions of RNA enzymes with RNA-joining activity, which were challenged to react in the presence of progressively lower concentrations of substrate. The enzymes that did react were amplified to produce progeny, which were challenged similarly. Whenever the population size reached a predetermined threshold, chip-based operations were executed to isolate a fraction of the population and mix it with fresh reagents. These steps were repeated automatically for 500 iterations of 10-fold exponential growth followed by 10-fold dilution.

They have a nice figure summarizing the system which I show below — and people should check out the article. Note – I can legally include this figure here because of the use of a broad Creative Commons License by PLoS Biology. Note – one of the stories I saw about this at Medgadget.Com also pointed out how they can use the article however they want because of where it was published. The power of true Open Access.

(A) The evolution chip is mounted on a temperature-controlled stage. Solutions containing polymerase enzymes (E) and mono- and oligonucleotide components (S) are delivered to the chip via capillary tubing and output to a pressure-controlled collection vial (O). A microscope objective is used to focus laser excitation (λex = 490 nm) on the microfluidic channel and to gather fluorescence (λem = 535 nm), which is detected with a confocal PMT. Valve actuation and fluid flow are controlled by six independent vacuum lines.

(B) The microfluidic device is shown with the active circuit filled with blue dye.

(C) The serial dilution circuit consists of a mixing loop with fluid flow channels (red), fluid access reservoirs (blue), and control valves (black). Fluid flow around the loop is controlled by three two-way valves (a, b, and c). Fluid access to the loop from the input reservoirs (RE and RS) and to the output reservoir (RO) is controlled by bus valves (in and out). The bus valves allow access when open, and prevent access while preserving fluidic continuity within the loop when closed.

(D) During operation of the circuit, the expanding RNA population is incubated while undergoing slow cyclic mixing until the fluorescence reaches a pre-determined threshold. Then an aliquot of the population is isolated between valves in and out as fresh solutions of E and Sin and out, and the aliquot is mixed with the fresh solutions by rapid serial actuation of valves a, b, and c. Open valves are indicated by filled circles; closed valves are indicated by a red X. are drawn into the loop and spent materials are delivered to the collection vial. Finally, the loop is sealed by closing valves

From: Darwinian Evolution on a Chip Paegel BM, Joyce GF PLoS Biology Vol. 6, No. 4, e85 doi:10.1371/journal.pbio.0060085

NIH Mandate on Open Access – Good First Step, Thanks to PLoS et al, but still a long way to go

Well, today is the day. The day after the new NIH mandate on Open Access (also see here for more information) to publications has begun. I think this is a great great day for science. And for society and Congress should be commended for doing something that is good for the country and the world that may have upset some of their big donors (i.e., the publishing industry).

And I think we all owe a big round of thanks to those who worked towards this goal. Clearly, there were many involved in convincing Congress to do this, from concerned members of the public, to SPARC and other NGOs, to tireless individuals like Peter Suber, and of course the Public Library of Science. For those who do not know, or may have forgotten, the Public Library of Science got it’s beginnings as an initiative to promote Open Access publishing (and it was not initially a publisher of journals). PLoS was founded by Harold Varmus, Pat Brown and Michael Eisen (my brother) in 2000. The first thing they did was circulate a petition to promote open access publishing. I signed the letter as did many many others. But alas, it was not enough. And so PLoS started its journals and many realized that it would be necessary for funding agencies to step in and require Open Access publishing for work they funded. And after a long struggle, we are now here with the new NIH mandate (as well as mandates from other agencies which got there before NIH). And I think that we all owe a big thanks to everyone behind this initiative. Also it is worth checking out Harold Varmus’ essay today on the new NIH initiative in PLoS Biology.

I note, however, that the NIH policy is only a first step. It does not move us completely towards true Open Access to scientific publications. There are still issues that need to be addressed, including the timing of release of publications (I think everything should be released immediately, not after a 6 or 12 month delay), the issue of Copyright, the need to get old publications into the public domain, and how putting material in Pubmed Central does not completely open it up to the world (see Peter Murray-Rust’s very interesting discussion of this on his blog). So there is still much work to be done. But nevertheless, I am happy to be living in this new world where NIH has made OA a key part of it’s mandate.

Congrats to Amy Harmon: Pulitzer for DNA Age Stories.

Congrats to Amy Harmon, reporter for the New York Times, who writes a lot about DNA (see all the DNA Age stories), who won one of those Pulitzer things today. I guess, maybe leaving me out of one of your last stories was a good call. I have written about her stories before a few times and overall, I like her reporting. What we all really need to do is convince her to start a blog. Print media is so 21st century.

Also see some other stories:

Passing of Jeremy Knowles

I write with sadness that Jeremy Knowles has passed away. Knowles was a Professor at Harvard, had been Dean of the Faculty of Arts and Sciences at Harvard, and an HHMI Trustee, among many things. I did not know him well, but I did have a recent scientific exchange with him regarding analysis we were doing of the Tetrahymena genome. Knowles has asked a question to Peter Bruns, who is a Tetrahymena guru (and also was at HHMI). The question related to intron splice junctions and whether that might support a paper he had written in 1992. The science here is not important.

I wrote back, basically saying we were sequencing the genome but alas our data might not be useful for his question since most of what we were doing at the time was predicting gene splice sites not actually determining them for real. And I said, in fact, much of the data in Genbank was also predictions not real cDNAs.

I expected him to be a bit disappointed. But instead, he wrote back to Peter:

Peter:
Thank you! Jonathan’s response confirms that I was right to ask an expert. For if I had gone fishing in the gene bank pool, I should probably have drowned. I shall wait, calmly.
best,
Jeremy

What I was struck with was his sense of humor and warmth, which emanated from this and a few other simple email messages. Based on these communications, I was looking forward to interacting with him again as we are now writing up a paper including all of our new cDNA data (real sequences, not predictions). I am sorry to see him go.

Tree of Life Art

As someone who studies the “Tree of Life” in terms of evolution (the tree of life is an evolutionary tree relating all life forms) and who even named his blog after this, I am fascinated by different portrayals of the Tree of Life. We can see lots of things like the Tree of Life in the real word. Much of this is due to the use of the Tree of Life imagery by various religious groups. Some of it is more connected to evolution in some way. But whatever the inspiration, there are some pretty nice representations out there. And I am posting one of them today. At UC Davis the UC Davis Arboretum is a really spectacular place. I go walking there all the time and take my kids to play there and watch the ducks and other animals. One day, I was walking near some gardens that they have been renovating for a while, when I saw they had unveiled some new artwork.

Below are some pictures of this artwork.  I am going to start posting more “Tree of Life” art here in the future and would love to get examples from people out there too.

http://picasaweb.google.com/s/c/bin/slideshow.swf

More on Tree of Life art in Arboretum

As someone who studied “The tree of Life” in terms of evolution I am fascinated by the Tree of Life art in the Arboretum.  Here are some more pictures

http://picasaweb.google.com/s/c/bin/slideshow.swf

Can a spoof be scooped by reality?

Well, if you read this blog, or a few others, you may already know that what I reported on here on April 1 regarding NIH cracking down on brain doping, was, in fact an April Fool’s joke. I will write more about this joke later and how we planned it, starting at something called scifoo camp at Google headquarters in the summer of last year. But I do want to write about one thing here — we sort of got scooped by reality. I had been planning for some time to do an April 1 joke on performance enhancing drug use among scientists. And as I was recruiting others to be involved in this plot, reality got in the way when Nature and then the New York Times started to report on brain doping as a real issue. It kind of took the absurdity away from our joke and made it seem like we were making some real commentary on brain doping when in fact, we were at least originally just trying to come up with something ridiculous but possibly believable at first look.

And now it has happened again. The second spoof I considered doing was to write about doing DNA and drug testing on some water bottles I collected from the Tour of California – a bike race that came 1 block from my house. I went for a little ride on the route of the race a few minutes after the peloton came by and got about 10 bottles from different teams. (This was real). And then I was going to pretend that we took those bottles and (1) figured out whose they were by DNA testing and (2) did drug tests of them. And this would allow me to write about 23 and me and other DNA testing companies as well as to make some fun of performance enhancing drug scandals. And I thought this would be ridiculous in a way because it could not possibly be legal to test someone’s DNA without any real just cause. And low and behold look at what comes along — Amy Harmon has an article in the Times yesterday on people doing exactly this type of thing — testing other people’s DNA (good article, by the way).

So now twice my spoofs end up getting scooped by reality. To me, a good spoof/April 1 joke is completely absurd in hindsight even if it is believable initially. So every time one of these jokes/pranks I want to pull gets close to reality, it becomes much much less funny to me. Who knows, maybe Craig Venter will in fact sequence his own microbiome, as I joked about last April 1.

Maybe before my next joke, I should call up Amy Harmon and other reporters to make sure they are not working on related stories first?

Open Evolution: Google supports open source code for evolutionary studies – Deadline 4-08 for Summer of Code

See email I received via Iddo Friedberg from the National Evolutionary Synthesis Center which is seeking students and others to participate in the Phyloinformatics Summer of Code.

This is just a reminder that the student application period ends
definitively on April 7 (Monday), 5pm PDT/8pm EDT (0:00 UTC on April
8). (Google extended the period from the original end date of March
31.) There are still a few project ideas that have received little
attention from student applications so far. If you are interested,
please see below for URLs, and get in touch with us phylosoc {at}
nescent {dot} org to inquire for more information re: application
status of your favorite project(s).

Phyloinformatics Summer of Code 2008
http://phyloinformatics.net/Phyloinformatics_Summer_of_Code_2008

*** Please disseminate this announcement widely to appropriate students
at your institution ***

The National Evolutionary Synthesis Center (NESCent: http://
www.nescent.org/
) is participating in 2008 for the second year as a
mentoring organization in the Google Summer of Code (http://
code.google.com/soc
). Through this program, Google provides
undergraduate, masters, and PhD students with a unique opportunity to
obtain hands-on experience writing and extending open-source software
under the mentorship of experienced developers from around the world.

Our goal in participating is to train future researchers and
developers to not only have awareness and understanding of the value
of open-source and collaboratively developed software, but also to
gain the programming and remote collaboration skills needed to
successfully contribute to such projects. Students will receive a
stipend from Google, and may work from their home, or home
institution, for the duration of the 3 month program. Students will
each have one or more dedicated mentors with expertise in
phylogenetic methods and open-source software development.

NESCent is particularly targeting students interested in both
evolutionary biology and software development. Project ideas (see URL
below) range from visualizing phylogenetic data in R, to development
of a Mesquite module, web-services for phylogenetic data providers or
geophylogeny mashups, implementing phyloXML support, navigating
databases of networks, topology queries for PhyloCode registries, to
phylogenetic tree mining in a MapReduce framework, and more.

The project ideas are flexible and many can be adjusted in scope to
match the skills of the student. If the program sounds interesting to
you but you are unsure whether you have the necessary skills, please
email the mentors at the address below. We will work with you to
find a project that fits your interests and skills.

INQUIRIES:
Email any questions, including self-proposed project ideas, to
phylosoc {at} nescent {dot} org.

TO APPLY:
Apply on-line at the Google Summer of Code website
(http://code.google.com/soc/2008), where you will also find GSoC program
rules and eligibility requirements. The 1-week application period for
students opened on Monday March 24th and runs through Monday, March
31st, 2008.

Hilmar Lapp and Todd Vision
US National Evolutionary Synthesis Center

=====
URLs:
=====

2008 NESCent Phyloinformatics Summer of Code:
http://phyloinformatics.net/Phyloinformatics_Summer_of_Code_2008

Eligibility requirements:
http://code.google.com/opensource/gsoc/2008/faqs.html#0.1_eligibility

Stipends:
http://code.google.com/opensource/gsoc/2008/faqs.html#0.1_administrivia

Quote of the week "There are much yummier and easier things to eat in the human body"

An interesting new paper has appeared in one of the those non Open Access journals – Science. Normally I do not write about such closed access, closed minded things, but I want to make an exception here. The paper is by George Church and colleagues on bacteria that subsist on a diet of antibiotics.

The paper is perfectly reasonable, if not pretty cool. Although it is a bit over hyped. It is obvious that bacteria would be able to eat antibiotics. Not only has this been shown previously, (as Church is very careful to point out) but bacteria eat anything and everything. So of course they will eat energy rich antibiotic molecules. The real problem in this case is the fear mongering that will come with the reporting on this. In the first few articles we already see this. For example, Reuters says

Church said the finding underscores the extent to which bacteria have developed resistance to antibiotics, a process that started almost as soon as penicillin was introduced in the 1940s.

Ummm … antibiotics have actually been around for billions of years. Microbes make them all the time. So resistance too has been around for a long time. Yes, we are selecting for strains resistant to all our classes of antibiotics. But resistance itself did not start with the introduction of penicillin. I note the AP story got this right:

Nor is it a surprise that soil bacteria can withstand some antibiotics; some had already been found. After all, a number of antibiotics are natural — think penicillin. Some antibiotics have been derived from soil.

The only sense in all the stories I saw came from Jo Handelsman who was quoted in many of them:

“Thank goodness we have those bacteria to eat at least some of the antibiotics,” said bacteriologist Jo Handelsman of the University of Wisconsin-Madison, who wasn’t involved in the study. “Nature’s pretty effective.” From AP article.

Even better, Handelsman tried to calm the fears about whether bacteria would eat antibiotics given to treat infections:

But bacteriologist Jo Handelsman of the University of Wisconsin, Madison thinks this is unlikely, as “there are much yummier and easier things to eat in the human body.”

And for that, she gets the quote of the week.

Open Access metagenomics selections

A quick post — here are some relatively new interesting papers in metagenomics that are fully Open Access