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

Open Access metagenomics selections

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


Yoga and Evolution – How are they related?

Trick question. They are related because I am posting YouTube videos on those topics here. Just a little YouTube humor to help everyone get through the week. Warning – the evolution one is truly over the top and might offend a few so click on it with caution.

EnlightenUp The Film

Dawkins Rap

Bill and Melinda (Gates that is) ask for your ideas … lots of money on the line

Well, I signed up for emails from the Bill and Melinda Gates Foundation, hoping to apply for some of their trillions of dollars to do a little bit of research.

And I got an email today I would like to share, since, well, they said I should share it. And here it is ..

The Bill & Melinda Gates Foundation is now accepting grant proposals for Grand Challenges Explorations, a US$100 million initiative to help scientists pursue innovative ideas for solving major global health problems.

Grant proposals are being accepted online at www.gcgh.org/explorations until May 30, 2008, on the following topics:

— Creating new ways to protect against infectious diseases
— Creating drugs or delivery systems that limit the emergence of resistance
— Creating new ways to prevent or cure HIV infection
— Exploring the basis for latency in TB

Initial grants will be $100,000 each, and projects showing success will have the opportunity to receive additional funding of $1 million or more. Full descriptions of the topics and application instructions are available at www.gcgh.org/explorations.

We are looking forward to receiving innovative ideas from scientists around the world and from all scientific disciplines. If you don’t submit a proposal yourself, we hope you will forward this message to someone else who might be interested.

Thank you for your commitment to solving the world’s greatest health challenges.

###
Bill & Melinda Gates Foundation

Guided by the belief that every life has equal value, the Bill & Melinda Gates Foundation works to reduce inequities and improve lives around the world. In developing countries, it focuses on improving health, reducing extreme poverty, and increasing access to technology in public libraries. In the United States, the foundation seeks to ensure that all people have access to a great education and to technology in public libraries. In its local region, it focuses on improving the lives of low-income families. Based in Seattle, the foundation is led by CEO Patty Stonesifer and Co-chairs William H. Gates Sr., Bill Gates, and Melinda French Gates.

Davis Life Magazine

Just got an email announcing a new issue of Davis Life Magazine which I meant to post about here previously. It is a nice little web magazine about, well, life in Davis.

Metagenomics Education

Just a quick one here. I was reminded recently about an interesting publication about metagenomics education in which some people might be interested. It is by Anne Jurkowski, Ann Reid and Jay Lebov and was published in a journal called CBE Life Sciences Education. This journal, though not fully Open Access is freely available online.

I think the article is a useful callto arms for educators to get ahead of the curve and to start thinking about ways to teach metagenomics BEFORE it becomes an old field (i.e, while it is hot, and who knows how long that will last).