Methagora

Talking points

2008-04-29T18:00:00Z

In the May Editorial, Nature Methods' Editors list their top ten pet peeves about conference presentations. Check out the list and add your tips!

Compare and conquer

2008-03-28T18:00:00Z

Experimental comparisons of methods, technology platforms or reagents are time-consuming and expensive, but hugely beneficial. An Editorial in the April issue of Nature Methods illustrates how such comparisons have been very useful for scientists in various research disciplines. Nature Methods has now adopted an article format called ‘Analysis’ to accommodate publication of such comparative analyses. Broad guidelines of what the editors will be looking for are provided in the April Editorial.

Proteomics data deposition to public repositories

2008-02-28T18:56:07Z

Starting in March, Nature Methods strongly recommends deposition of proteomics data to public repositories before manuscript submission. An Editorial in the March issue describes the motivation of this decision and comments on the public repositories that are now available to proteomics researchers.

We welcome your comments on this move.

Next-next DNA sequencing

2008-02-28T14:45:52Z

While the technology feature, “DNA sequencing: generation next-next”, was at press, Pacific Biosciences of Menlo Park, California stunned the community with their announcement of a single molecule sequencing technology they claim will provide a complete human genome in 15 minutes by the year 2013. Although Pacific Biosciences was founded in 2004, the company had been very ‘hush hush’ about their technology development. But that veil of secrecy was lifted during the Advances in Genome Biology and Technology meeting held February 6th to 9th at Marco Island, Florida where Stephen Turner, chief technology officer, presented the first preliminary data on the system.

]]> According the company’s website, their single molecule sequencing method, called SMRT for ‘single molecule, real time’, is based on a zero mode waveguide which helps create very small detection volumes. The reaction is performed in a well that is 70 nanometers wide and holds only 20 zeptoliters (10E-21 liters) of detection volume occupied by a single molecule of polymerase. The key to the technology is illuminating around the polymerase, but not above, as it incorporates each fluorescently tagged nucleotide into an elongating strand of DNA. The remaining nucleotides are above the polymerase, in the dark, thereby greatly reducing background fluorescence which has been an issue for other developers. As each nucleotide is incorporated by the polymerase, its fluorescence is detected by a CCD camera and the fluorescent tag is cleaved, leaving the elongating DNA in a native form.

With a described sequencing rate of 10 bases per second, in real-time, performed across thousands of these wells on the chip, the Pacific Biosciences instrument would provide faster sequencing than any other machine available today. While they hope to have an instrument ready for 2010, they are targeting 2013 for the arrival of a model that can deliver the stunning 15-minute genome. The company is still working to reach that target by increasing the number of zero mode waveguides on a chip to one million and modifying the polymerase to increase incorporation to 50 nucleotides per second. With these enhancements they are projecting a mind boggling 100 gigabases/hour.

So, what is your opinion of all the effort going into ‘next-next generation’ sequencing technology and the stir that it has created? And if a ‘15 minute genome’ becomes reality -- what are the first things that should be done using such a technology?

Nathan Blow, Technology Editor

Structural genomics in the spotlight

2008-01-30T15:09:58Z

Check out Nature Methods' February 2008 issue, featuring several methodological aspects of structural genomics and structural biology. A Commentary provides an overview of the efforts of the US-based Protein Structure Initiative, a Review from multiple, worldwide structural genomics consortia provides a consensus strategy for expressing and purifying recombinant proteins, a Perspective provides a user-friendly guide to protein crystallization, and the Technology Feature shows a day in the life of a structural genomics facility. Additionally, the Editorial discusses some of the criticisms that structural genomics efforts have faced, as well as some of the beneficial results.

What are your thoughts about structural genomics? Share your comments here!

Method of the Year

2007-12-20T15:50:16Z

Nature Methods has named next-generation sequencing its inaugural Method of the Year.

Check out the special feature (freely accessible online) with Commentaries by Stephan Schuster and by Barbara Wold and Rick Myers. In addition to celebrating the Method of the Year 2007 the special feature contains a shortlist of Methods to Watch in the years to come.

Here, we welcome your comments on our choices as well as your suggestions of other methods to keep an eye on. We firmly intend this event to become an end-of-the-year tradition, and we hope for your participation in next year’s nominations!

An intelligently designed response

2007-11-29T19:55:29Z

Sooner or later, any scientist is likely to be confronted by a supporter of “intelligent design” (ID), or questioned by a student, friend or neighbor intrigued by the concept of ID. Check out our idea of a response here and share your thoughts on what yours would be.

Wishing and hoping for mass spectrometry

2007-11-29T19:33:55Z

In this month's Technology Feature several key developers of mass spectrometry technology share their wishes for the future of this technology. Did your hope for the next innovation in mass spectrometry make the list? If not, here is your opportunity to add wishes, hopes or comments – and let the developers know what advances you would like to see in the coming years.

Research in situ, where it is most needed.

2007-10-23T03:37:20Z

The Global Theme Issue on Poverty and Human Development went live today: 235 scientific journals coordinated the publication of articles specifically addressing issues related to human condition in poverty-stricken areas. This initiative was spearheaded by the Council of Science Editors and the full list of articles can be found on their web site. A special event was hosted at the US NIH on the occasion of the coordinated publication.

]]> Nature Publishing Group has contributed Commentaries, Editorials, News Features and Reviews in different areas, approaching the problems from a wide range of perspectives corresponding to the specific interest of each participating journal. The assortment of articles range from a user-friendly guide to evaluating diagnostics for visceral leishmaniasis to the possible applications of nanotechnology to provide potable water.

In Nature Methods’ pages, Robert Grant discusses the methodological needs associated with conducting research on HIV/AIDS and tuberculosis in underprivileged regions. Grant is Associate Investigator at the J. David Gladstone Institutes and Associate Professor of Medicine at UCSF; he conducts trials on pre-exposure prophylaxis for prevention of HIV transmission. In his Commentary, he builds a case in favor of doing research where such devastating epidemics hit the hardest, illustrating how it can benefit health care worldwide. In a related Editorial, Nature Methods takes a look at the challenges laying ahead for methods developers to come up with diagnostic methods adapted to detect infectious diseases in poverty-stricken areas.

Share your thoughts on these issues.

Mass spectrometry in focus

2007-09-27T20:31:45Z

Mass spectrometry has become the most powerful tool for proteomics, owing to its high-throughput capacity and molecular information yield. However, it is perhaps under-utilized in more traditional cell biology research, since historically, it was a tool developed by and for chemists. Our October issue celebrates this technology and its established and emerging biological applications with a special Focus on mass spectrometry in proteomics applications.

A 'rough guide' to publication.

2007-08-30T22:01:54Z

The process of getting a manuscript published can be a long and sometimes convoluted one. The more transparent it is, however, the more likely that members of the scientific community will be able to negotiate it to their benefit. In our September editorial, we provide a brief primer on key steps in the process, especially those where problems are likely to be encountered.

Receptor dimerization revisited

2007-07-30T21:30:53Z

Last December we published an Article by Simon Davis and colleagues challenging the conventional methodology being used in BRET studies that detect dimerization of G protein coupled receptors. The conclusions were contested in a Correspondence by Michel Bouvier and colleagues. In a new Correspondence, a former member of the Bouvier lab further argues against the results and conclusions of the Davis study with experimental results using the 'Type 2' BRET assay of Davis and colleagues.

]]> It is difficult to draw firm conclusions regarding the accuracy of the disparate results. Both sides have reasonable arguments. The use of known dimerizing and non-dimerizing controls to validate their method in the original report by Davis and colleagues argues for the accuracy of their method in general. Unfortunately, the 'Type 1' assay which is the basis of their conclusions is difficult to set up properly compared to conventional or 'Type 2' BRET assays.

Regardless of whether or not GPCRs dimerize in vivo, it is clear from the arguments being made that great care must be taken to ensure that BRET experiments are set up properly and expression levels of the putative interacting proteins are carefully validated.

What are your experiences using BRET to detect receptor dimerization? Is there a simple explanation for these disparate results that is being overlooked? Are further developments of the assay needed to easily ensure that receptor expression is at endogenous levels while still providing a strong signal? Share your thoughts.

No faulty-gene carrier need apply

2007-07-30T19:00:00Z

A bill designed to prohibit discrimination based on genetic information in terms of health insurance and employment is awaiting a vote in the US Senate. There have been several similar but ultimately unsuccessful legislative attempts over the past 12 years. It is crucial that this bill be enacted into law to address a public fear likely to limit patient access to predictive genetic testing and to discourage participation in genetic research.

]]> The August Editorial examines how the Genetic Information Nondiscrimination Act of 2007 (GINA 2007) would put a long-awaited end to a patchwork of state laws (see the National Conference of State Legislatures website for a view of the current situation).

The NHGRI Ethical, Legal, and Social Implications (ELSI) research program website has a lot of information on GINA 2007, including a timeline of previous and current legislative attempts, studies on genetic discrimination in the US, as well as the report accompanying the bill in the Senate.

As the editorial discusses, the legal situation is a similar patchwork in Europe. Many countries have signed the Convention for Human Rights and Biomedicine in 1997, but there are notable absences and not all signatories have ratified the Convention (see list of signatures and ratifications on the Council of Europe website). According to a recent report by the EU-funded project EuroGentest, even ratification of the Convention has not leveled discrepancies between national laws.

This confusing legal situation is not an encouraging context for genetic research and it will prevent individuals from fully benefiting from the progress of genomic medicine. If the US finally enact the federal law contained in GINA 2007, this should constitute a serious incentive for European countries to follow suit.

Staff picks

2007-06-28T13:31:06Z

In an editorial in the July issue, we suggest some recent popular science books that would make a nice summer read and hope that summer will not be the end of it. To keep you going, here are an extended list of older books, including some of our favorites and some of the genre classics. The list was assembled with the kind advice of editors, scientists and science writers.

]]> In no particular order:

The Blind Watchmaker by Richard Dawkins—although the tone tends to be of the lecturing kind, the clarity of the argument is amazing and this is a must read if you will ever encounter skeptics of evolution theory
Consilience by Edward O. Wilson (and his memoir Naturalist)—an erudite argument for the unity of human knowledge, bridging gaps between areas of science and humanities.
The Elegant Universe by Brian Greene (or his The Fabric of the Cosmos, depending whether you have a soft spot for string theory or relativity)
The Double Helix by James Watson—a first-hand account of the discovery of the structure of DNA (Francis Crick’s A Mad Pursuit is another first-hand account which makes a nice companion to Crick’s biography mentioned in the editorial)
Galileo’s Daughter by Dava Sobel—a human touch brought brilliantly to the biography of Galileo, and the historical conflict between science and religion, based on his correspondence with his illegitimate daughter, the nun Suor Maria Celeste.
Genius, James Gleick’s entertaining and science-heavy biography of Richard Feynman (consider also the biography of Isaac Newton by the same author)
Guns, Germs and Steel by Jared Diamond—a Pulitzer Prize-winning history of human civilizations from the biologist’s perspective (and his more recent Collapse analyzing the fall of human societies)
Right Hand, Left Hand by Chris McManus—won the Aventis Prize for Science Books in 2003 and offers an erudite reflection on the breaking of symmetry in nature at multiple scales—molecules, cells, organisms, and culture.
Natural Obsessions by Natalie Angier—a science writer’s 1988 account retracing the events that lead to the discovery of the ras oncogene.

If you would rather go for short stories, watch for the 2007 editions of The Best American Science (and Nature) Writing series coming out in the fall.

As we have said before, this is not an authoritative list, so feel free to send us your suggestions for additions and your comments on what these books can bring to a scientist.

Happy summer reading!

The quest for the antibody grail

2007-06-07T00:09:52Z

One of the most common frustrations among biologists is the difficulty to get their hands on a good antibody with a decent chance to work well in the particular assay they have in mind.

There is not one universal quality control test for antibodies and many commercial antibodies which are advertised to work well, say, in Western blot will perform poorly in immunoprecipitation and abysmally in a FACS machine. Examples abound and researchers often lament about the money spent on re-testing antibodies or repeating experiments that have failed due to poor antibody quality.

]]> A Technology Feature published in Nature today explores the ongoing (or planned) large-scale initiatives, in several attempts to generate better antibody resources. Among the notable initiatives, which have already achieved results, are the Sweden-based Human Protein Atlas and the Sanger Institute Atlas of Gene Expression. Other particularly ambitious projects in the starting blocks are the NCI Clinical Proteomics Technologies for Cancer and the European-based ProteomeBinders initiatives. The whole lot of efforts is being watched by HUPO Antibody Initiative.

We have written before about the difficulties faced by such initiatives and in particular, the nascent ProteomeBinders. But the good news is the different approaches seem to be gathering momentum. Hopefully, funding agencies will acknowledge the need to support such efforts and commercial manufacturers will join the fray.