This year’s Nobel Prize in Chemistry has been awarded to Osamu Shimomura, Martin Chalfie and Roger Tsien for the discovery and development of Green Fluorescent Protein as a research tool. GFP has revolutionized many aspects of biological research, allowing for real-time imaging of living specimens, rather than the difficult task of trying to piece together a process from a series of dead, fixed and stained specimens. Quoting from DNA Science:

“In the early 1960’s, Osamu Shimomura and Frank Johnson at Princeton University collected specimens of jellyfish in studies to understand their “bioluminescence.” One of the compounds they discovered was named green fluorescent protein (GFP) because it glowed bright green under UV light. Many years later, in 1992, Douglas Prasher at the Woods Hole Oceanographic Institute cloned a cDNA for GFP. In 1994, Prasher and Martin Chalfie at Columbia University were the first to realize the potential for use of GFP as a reporter molecule.”

Tsien comes into the story later, and has been instrumental in understanding how GFP works, and in extending the color palate beyond green into a wide variety of wavelengths, allowing for multi-spectral analysis of many labeled objects at the same time.

CSH Protocols has many articles detailing the use of GFP (with more continually on the way). You can see a list of available protocols here.

The October issue of CSH Protocols presents a new focus on Emerging Model Organisms.

Much of twentieth century biological research has focused on a limited number of model organisms, such as Arabidopsis, C. elegans, mouse, Drosophila, and E. coli. These classical model species, chosen because they are amenable to laboratory research and suitable for studying a range of biological problems, have served to elucidate many biological processes that can be generalized across a wider array of organisms. It is only a slight exaggeration to say that the basic workings of the cell were elucidated mostly from experiments on a few single-celled organisms — primarily E.coli and yeast. Our understanding of animal development was largely based on the genetics of fruit fly and worm and on the manipulation of a handful of amphibians and mouse; most of what we learned about the molecular and developmental biology of plants came from examining Arabidopsis and just a few other species. But biology wasn’t always done this way.
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I’ve written about Zotero before, it’s an intriguing tool, essentially a Firefox plug-in for managing your reference list and other pieces of information. It’s a bit of a hybrid between online management tools like Connotea and things like Papers which you store on your own computer.

The bad news is that Thomson Reuters, the manufacturers of EndNote, are suing George Mason University and the Commonwealth of Virginia because a new version of Zotero lets you take your EndNote reference lists and convert them for use in Zotero. Yes, this is the same Thomson of Thomson ISI, secret gatekeepers of journal impact factors. They really seem to be going out of their way to lose what little goodwill they have left with the scientific community. It will be interesting to see if this reverse engineering for interoperability holds up in court as something that should be prevented.
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Some interesting recent articles on Web 2.0 and Publishing:

EmTech inanity
Ever since Dan Lyons abandoned his Fake Steve Jobs persona, his blog has gone way downhill (and his Newsweek articles have been generally lame as well). But when he fires on all cylinders, he can still put out some of the funniest, most scathing commentary you’ll find on the tech industry. Here he reviews a conference panel of some of the biggest names in Web 2.0 and really nails the failings of so many of these tools, particularly those launched for scientists: they’re solutions in search of problems:

“If I were funding these guys I might go home scratching my head about what those kids are doing with all of my millions. Maybe there is a point to what they’re doing, but honestly, what great problem are these companies trying to solve? Sitting there watching this spectacle — watching these guys unable to simply explain what they do and and how they are going to make a business out of it – it was staggering to think that someone has entrusted these people with very large sums of money.”

Lyons further hammers home his message by noting that the participants all spoke about “how they had been trying to find a good restaurant in Boston and how their cool social networking tools and collaborative filters had enabled them to do such a great job of this restaurant hunting task.” The restaurant they found? The Union Oyster House, a dreadful tourist trap that anyone who has lived in Boston knows to avoid. Also, the quote of the week can be found in the article’s comment section:

“…the unspoken agreement of Web 2.0 seems to be that there is nothing more terrible than having to spend even a second alone with one’s own thoughts.”

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Recently, the NY Times had an article discussing the concept of “ambient awareness”, or as the article puts it, “incessant online contact”. Now, first off, I have to admit that I’m one of the over-30-year-olds the article mentions, who finds the concept of subjecting others to (and being subjected to) a stream of trivial details about one’s day completely unappealing. The proponents of Twitter and FriendFeed and the like feel that they’re getting a more intimate understanding of people, “something raw about my friends,” as one user puts it. I’m more in line with the critics quoted in the article that the end result is more “parasocial” than social, and that it ends up an extension of reading gossip magazines and following celebrities from afar.

So how do these new practices apply to the world of science research?
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John Mundy’s laboratory at the University of Copenhagen has written up protocols for Coimmunoprecipitation (co-IP) of Nuclear Proteins and Chromatin Immunoprecipitation (ChIP) from Arabidopsis in the September issue of CSH Protocols. co-IP is useful for identifying and isolating protein-protein interactions and protein complexes. ChIP allows the analysis of protein-DNA interactions, and is a technique currently seeing widespread use as the field of transcriptional regulation continues to make great advances. One advantage to this set of techniques is that the nuclear lysis buffers standard in most protocols for plant nuclear protein extraction are incompatible with co-IP. Here, nuclear protein extraction is accomplished via sonication in co-IP buffer and treatment with Benzonase, which results in material that can be used with co-IP.

As always, catching up with some interesting articles regarding publishing, science and Web 2.0:

Beyond the Flickering Screen: Re-situating e-books
An excellent article, and one of the best, most realistic takes I’ve seen on the future of e-books. The author argues that while cost plays some factor in the failure of e-books to catch on (a Kindle purchaser needs to buy 61 books before they break even on the purchase of their device), the real problem is a cultural one:

“The idea of electronic books, or e-books, remains the domain of geeky early adopters. The reasons for this are manifold, but, arguably, a broader uptake of e-books has not occurred because cultural change is much more difficult than technological change and book readers have yet to be persuaded to change their cultural habits.”

He suggests that one solution for this is to make e-books ubiquitously available, rather than limiting them to a separate e-book-reader-only ghetto. To reach a mass audience, e-books need to be a common part of the sort of things one does online or with the electronic devices one already owns:

“The availability of e-books on mobile platforms may not result in more people embracing longer-form literature. But it will increase the number of people actually reading, and, just as casual gaming has attracted a female demographic, the instant availability of appropriate reading material might sway some of those men who appear to be reluctant readers.
Rather than focus on printed books, and book-like reading devices, the industry should re-position e-books as an easily accessible content choice in a digitally converged media environment. This is more a cultural shift than a technological one—for publishers and readers alike. Situating e-books in such a way may alienate a segment of the bookloving community, but such readers are unlikely to respond to anything other than print on paper. Indeed, it may encourage a whole new demographic—unafraid of the flickering screen—to engage with the manifold attractions of “books.””

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The September issue of CSH Protocols is now available online, and this month brings a set of nine protocols from Renee Reijo Pera’s laboratory at Stanford describing methods for the generation, maintenance and analysis of human embryonic stem cells (hESC). With the upcoming presidential elections, and both candidates favoring expanding federal funding for stem cell research (and one vice presidential candidate agrees, the other, not so much), the near future should see increased usage of these valuable research techniques. Two of these hESC protocols are featured in this month’s issue (our featured protocols each month are available to subscribers and non-subscribers alike).

Noninvasive Human Nuclear Transfer with Embryonic Stem Cells describes the transfer of a nucleus from a somatic cell to an enucleated oocyte for reprogramming to an embryonic cell state. Older methods commonly use Hoechst and UV light, which can lead to DNA damage. Here, a polarized microscopic imaging system is used to visualize the meiotic spindle without DNA staining and UV illumination.

Culturing Human Embryonic Stem Cells in Feeder-Free Conditions describes the culture of hESCs in feeder-free conditions on Matrigel with MEF-conditioned medium. This protocol can be used for applications such as genetic modification of hESCs without feeder cell contamination.

Extravasation is the process by which circulating tumor cells pass through the walls of blood vessels. August’s issue of CSH Protocols features an article from Duke University’s Xiao-Fan Wang and colleagues describing in vitro assays for measuring this critical step in metastasis. Human umbilical vein endothelial cells (HUVEC) are grown as a monolayer on a membrane to simulate a vessel wall. The transendothelial cell migration (TEM) assay looks at the efficiency of migration through the monolayer, while the vascular permeability assay looks at the effect on permeability of various secreted ECM proteins. As with all featured articles in CSH Protocols, In Vitro Assays for the Extracellular Matrix Protein-Regulated Extravasation Process is freely available to subscribers and nonsubscribers.

I’m happy to say that this week we sent out our first round of royalty payments to authors of original articles in CSH Protocols. Because we’re doing some reprinting of material from our already-published laboratory manuals, we built in a system to pay royalties to the editors of those manuals. We chose at the time to extend those royalties to authors of new material as well. The idea of writing up methods isn’t something that immediately occurs to most laboratories–they’re usually more interested in publishing data, so we’re hoping that these royalty payments will at least serve as something of a motivation for publishing (and continuing to publish) protocols with us. We’re not talking about huge sums of money, but as I recall from my graduate student days, every little bit helps. It also addresses one of the complaints one hears about us greedy science publishers–that we fail to compensate scientists for the work they’ve put into the publication and keep all the cash for ourselves. While CSHL Press is part of a not-for-profit research institute, and any money we make from our publications goes to fund research at Cold Spring Harbor Laboratory, we’re very curious to see what happens from this experiment in revenue-sharing. Does this make a difference to you as an author?

This set of royalties covers the calendar year 2007. A portion of our subscription revenue is set aside and divided among all authors/editors based on the usage of their individual articles during that calendar year. Those who published articles late in the year may not see much in terms of revenue given the relatively small time scale that their articles were available, but hopefully their articles will see a little more use in 2008.