To Find a New Treatment

With more and more cancers being parsed by their genetic mutations, even oncologists can have a hard time keeping up with the variants and which treatments go with them, the New York Times writes.

"There are so many genes and so many mutations," William Pao from Vanderbilt University tells the Times. "The human brain can't memorize all those permutations." He and some colleagues developed a website called My Cancer Genome to keep all those mutations and drugs straight for doctors and patients. For example, clinicians can search the database, which is maintained by a team of more than 50 people from 20 different institutions, for different cancers and mutations and then for related treatments or drug trials.

As the Times points out, to get to the stage of being able to search for treatments for a specific genetic mutation, that mutation first has to be uncovered, and there are more and more tools to do that, it adds. It highlights Foundation Medicine's $5,800 FoundationOne test that profiles tumor genomes.

Fadi Braiteh at the Comprehensive Cancer Centers of Nevada in Las Vegas tells the Times that he has used that test and, while it wasn't helpful for every patient, it did point to a new therapy for a lung cancer patient who was not responding to chemotherapy. "It gave me some guidance," Braiteh said. "We were able to give a drug we've never used before for this mutation."

Hang on, Little Tomato!

Ever take a big bite out of a supermarket tomato and think, "This is just delicious!"? Probably not. After decades of aggressive breeding to make the industrially grown vegetable more durable, the tomato doesn't taste much like a tomato anymore. But hang on, tomatoes, molecular scientists are pondering your palatableness, reports Steve Mirsky in Scientific American.

During a recent scientific meeting in Boston, Harry Klee, professor horticultural sciences at the University of Florida's Department Plant Molecular and Cellular Biology Program, said that although post-World War II "intensive breeding" techniques gave tomatoes a longer shelf life, these commercial gains came at the loss of taste. "Modern tomatoes focus on yields, basically making too many fruit at same time," Klee said during his talk. "The plant can't keep up with filling those fruits with nutrients. So the effect of what the modern breeders have done is basically to take the old tomatoes and add water."

Klee and his colleagues at UFL are working to infuse taste back into the tomato. The team of researchers had a panel of tasters rate heirloom tomatoes of old lineages, then they pulverized the vegetables and analyzed the chemical compounds that influence their taste. In their work, Klee and his colleagues have identified six volatiles – chemical compounds in the tomato that influence a person's sense of taste – that enhance sweetness and two that suppress sweetness.

"These volatiles can really fool the brain," writes Mirsky. For example, tasters rated the Martina tomato variety twice as sweet as the so-called Yellow Jelly Bean tomato, even though the Martina has less sugar. Tasters found the Martina sweeter because that variety has the six sweetness enhancing volatiles in higher concentrations than the Yellow Jelly Bean.

Given these findings, researchers are trying to figure out ways to breed more flavorful tomatoes that still hold up to the demands of mass production. "So that when you say tomato, I don't say blehhh," Mirsky adds.

This Week in PLOS

In PLOS Genetics, the University of Edinburgh's Pamela Wiener and colleagues from the UK and the Netherlands look at genetic signatures coinciding with diversifying selection in European pigs. The team used a pig-specific Porcine60K chip to assess SNP patterns in the genomes of pigs from 13 European breeds and their wild boar cousins. Using data from between two dozen and nearly three dozen pigs per breed, investigators tracked down genetic signatures and/or expression quantitative trait loci corresponding to several breed-specific traits — from color and ear shape to growth patterns and pork production-related features such as fat deposition. The data also revealed signs of past genetic mixing with pigs from Asian breeds, researchers note, study authors note, and point to places in the genome where the European breeds differ from wild boars.

A team from the Universities of Toronto and Minneapolis took a comparative proteomics approach to profiling intrinsically disordered regions in human proteins and their relationships to splicing and protein function. As they report in PLOS Computational Biology, the researchers focused on protein regions known for flexible or constrained disorder. While both types of conserved disorder tend to appear in parts of proteins that are prone to tissue-specific splicing, for instance, they found differences in disorder enrichment depending on the nature, location, and function of the protein-coding exons involved.

Exposure to aerosol forms of the hemorrhagic fever-causing Lassa virus prompts changes in immune gene expression that ultimately compromise effective adaptive immune response to the virus, according to a study in PLOS Neglected Tropical Diseases. Researchers from Boston University and elsewhere did array-based gene expression profiling on white blood cells from four non-human primates exposed to Lassa virus aerosols over the two weeks or so before each died from the disease. Based on the sorts of genes showing higher or lower expression at each stage of infection, the study's authors determined that Lassa virus spurs a strong innate immune reaction. But adaptive immune gene response apparently lagged, they note, perhaps due to negative regulation by the virus itself.

Building Better Beer Through Molecular Biology

Most brewers say that making beer is both a science and an art. Biotechniques reports this week that the science of brewing is making great strides thanks to molecular biology tools and technologies.

For instance, one group at Niigata University in Japan recently developed a method to isolate DNA from beer for subsequent PCR analysis. The group used some known primers and also designed novel primers based on species-specific DNA sequences from the main ingredients in beer — barley, yeast, and hops — then analyzed the quality and variety of those ingredients in 22 beer samples.

The Niigata University team also developed a magnetic bead-based sample prep method to separate DNA and eliminate PCR inhibitors from freeze-dried beer samples.

Using these techniques, the researchers were able to identify DNA from yeast, hops, barley, corn, soybean, and rice; and were able to detect 16 different barley cultivars across their samples — findings that they say could improve ingredient quality control or help brewers select the ideal malted barley for their elixirs.

Meantime, Biotechniques reports, James Madison University researcher Christine Hughey is using liquid chromatography-mass spectrometry to analyze her pint.

After a line of single-hop beers — concoctions all brewed in essentially the same manner save the variety of hops used — piqued her interest, Hughey applied LC-MS to identify the distinguishing chemical characteristics that each hop variety imparted to the beer.

Hughey is now developing software to pinpoint which molecular features are unique to a particular hop in a particular year.

Daily Scan reports that it is happy to be part of a blinded tasting panel to assess the results of these experiments — all in the name of science, of course.

Friends and Foes

The human body is teeming with microorganisms. "John Donne said 'no man is an island,' and Jefferson Airplane said 'He’s a peninsula,' but it now looks like he's actually a metropolis," writes Richard Conniff at Smithsonian magazine.

Conniff notes that recent technological advances have allowed researchers, through initiatives like the Human Microbiome Project, to get a glimpse of 10,000 or so species that call the human body home. Link between changes in the microbiome and disease, Conniff adds, are tantalizing researchers, some clinicians, and even venture capitalists. The public, too, he says, has been drawn in, especially intrigued by links made between the microbiome and obesity.

However, as Conniff writes, too much emphasis is sometimes placed on the role of the microbiome in health and disease with not enough evidence. "I believe the community of microbes that live in and on us is going to be shown to have major influences," Jonathan Eisen from the University of California, Davis, tells him, but Eisen adds that that “is different from actually showing it, and showing it doesn’t mean that we have any idea what to do to treat it."

Still, procedures like fecal transplants are increasingly being used to treat Clostridium difficile infections, and clinical trials of such treatments are underway.

"Coming to understand our microbes not as enemies, but as intimate partners could change our lives at least as dramatically, with time and proper testing," Conniff adds.

HT: Jonathan Eisen at the Tree of Life

Primate Center to Close

Harvard Medical School is shuttering its nearly 50-year-old primate research facility due to cost concerns, the Nature News Blog reports. The New England Primate Research Center currently houses about 2,000 monkeys, which the school says will be transferred to other primate centers or remain at NEPRC during the closure process, which could take two years.

In a statement, the school said that "driving the decision was the fact that the external funding environment for scientific research has become increasingly challenging over the past decade. Recent funding pressures have added uncertainty to this already-challenging fiscal context."

The center, blogger DrugMonkey points out, "lists an impressive series of accomplishments." That list includes contributions to establishing that AIDS is caused by a virus, developing nonhuman primate models of colon cancer and inflammatory bowel disease, and more.

NENPRC has also had its share of troubles. In a blog post, the Boston Globe says that the center had been cited by the US Department of Agriculture for animal welfare violations. The school says its decision to close the center was not related to these problems.

Nancy Haigwood, the director of the Oregon National Primate Research Center, is critical of the move to close the New England facility. "It's very, very disturbing, disappointing, disheartening, shocking," she tells the Globe. "I think it's going to be very, very difficult to imagine that the investigators impacted by this decision will be able to keep up their momentum. We're talking about very talented senior investigators who are at the peak of their careers."

One Step, One Checklist at a Time

Nature Publishing Group has announced a new initiative aimed at improving the reproducibility of research published in articles appearing across its spectrum of journals.

To help with the issue of reproducibility, the publishing company says in a press release it has developed a checklist to help researchers report the details of their methodologies. The checklist "focuses on a small number of often-incompletely reported elements of experimental and analytical design that are crucial to the interpretation of research results; it also consolidates several existing policies about data deposition and presentation," the statement adds.

Nature adds that it will also be changing some of its in-house practices, eliminating length restrictions on methods sections, and may consult with statisticians on certain papers.

It notes in an editorial, though, that this is but a "small step" toward solving the issue of reproducibility. "Tackling these issues is a long-term endeavour that will require the commitment of funders, institutions, researchers and publishers. …. We urge others to take note of these and of our initiatives, and do whatever they can to improve research reproducibility," the editorial adds.

This Week in Science

In this week's Science, a group of Max Planck Institute of Biochemistry researchers describe a new high-resolution mass spectrometric method for identifying and quantifying secreted proteins, demonstrating it on proteins released from immune cells upon receptor ligation. The work "enables a systematic dissection of signaling pathways and the identification of proteins with transcriptionally independent or unexpected extracellular functions," the researchers write.

Also in Science, Massachusetts Institute of Technology scientists Jeremy Wilusz and Phillip Sharp provide an overview of circular RNAs, which had previously only been found in pathogens, but recently have been discovered in a range of species, including humans. One circular RNA in particular is highly abundant in human brains and contains dozens of binding sites for a particular microRNA, miR-7. Because circular RNAs generally have multiple microRNA binding sites, Wilusz and Sharp suggest that other circular RNAs may also regulate the activity of microRNAs. They also propose that circular RNAs may act to bind and sequester RNA-binding proteins or "even base pair with RNAs besides microRNAs, resulting in the formation of large RNA-protein complexes."

Francois Jacob Dies

François Jacob, who won the 1965 Nobel Prize in Physiology or Medicine for his work on the genetic control of enzymes, has died, the Los Angeles Times reports. He was 92. Jacob worked with Jacques Monod and André Lwoff at the Pasteur Institute in Paris where they studied how the genes were translated to become proteins in the cell, uncovering messenger RNA and regulatory genes that control expression. Jacob and Monod also studied the lac operon in Escherichia coli, which usually eats glucose, but can survive on lactosewith the help of three enzymes.

"Through an elegant series of experiments, the researchers showed that the genes that serve as the blueprints for those three enzymes are each accompanied by another gene called the operator," the LA Times writes. "In this system, glucose acts as a repressor, binding to the operator and physically preventing the blueprint gene from being copied into messenger RNA."

Jacob, Monod, and Lwoff shared the Nobel, and in their introduction, Sven Gard from the Karolinska Institutet said they "opened up a field of research which in the truest sense of the word can be described as molecular biology."

Happy Double DNA Day

It's DNA Day, and as NIH Director Francis Collins writes in a blog post, it's a "double anniversary."

Sixty years ago, on April 25, 1953, Francis Crick and James Watson published their paper in Nature describing the structure of DNA, writing that their model has "two helical chains each coiled round the same axis" and "the novel feature of the structure is the manner in which the two chains are held together by the purine and pyrimidine bases. The planes of the bases are perpendicular to the fibre axis." That same issue of Nature included papers from Maurice Wilkins as well as from Rosalind Franklin and Raymond Gosling, Franklin's student.

Crick, Watson, and Wilkins went on to win the Nobel Prize in Physiology or Medicine in 1962; Franklin died of ovarian cancer in 1958. Recently released letters, LiveScience reports, indicate that the scientists who worked on the DNA structure were first nominated for the prize in 1960, but that many of the nomination letters did not mention Wilkins; none mentioned Franklin, though the award is not given posthumously. Crick, LiveScience says, wrote to Jacques Monod saying that Wilkins should be included; Monod, it turns out, sent his nomination letter to the chemistry prize committee. Experts speculate that the two committees shared nomination letters, LiveScience adds.

Also on April 25, but 10 years ago in 2003, researchers announced completion of the Human Genome Project's goals. In the intervening years, Collins writes that about 20,500 genes have been uncovered and about 54 million genetic variations have been noted. "I am a physician; my dream is to see these advances in understanding the genome translated into better methods of prevention, treatment, and cure of disease," he writes, later adding, "As we celebrate this special day, let's resolve to use all means possible to bring the promise of the genomic revolution to those billions of people in the world who are still waiting and hoping for its benefits to reach them."

If you are looking for a last-minute way to celebrate, the University of Hull's Mark Lorch gives directions in the Guardian on how to make a model of DNA from licorice and gummy candy as well as on how to extract DNA from kiwifruit.

Tradition!

"Until recently, in vitro diagnostics were priced nearly at commodity levels and were relegated to the backwaters of the life science universe," Soren Peterson, Vivek Mittal, and Kristen Pothier write this month in In Vivo.

Lately, though, that's changed, says the trio, made up of a senior analyst, VP, and partner, respectively, of life sciences strategy consulting firm Health Advances.

With the emergence in recent years of high clinical value molecular diagnostics, they write, developers of such tests have become attractive acquisition targets with traditional clinical and laboratory firms like Quest Diagnostics and Beckman Coulter now competing with nontraditional buyers such as pharma firms, life science tool companies, and diversified conglomerates that have entered the sector.

In fact, they write, deals between diagnostics firms and such nontraditional buyers have grown from 33 percent of molecular diagnostic M&A in 2007-2008 to 63 percent in 2011-2012.

Among the Dx firms the authors think are currently primed for acquisition? BG Medicine, Biodesix, CardioDx, and a number of other names no doubt familiar to GenomeWeb readers.

This Week in Nature

In Nature Biotechnology this week, a team led by Columbia University researchers report on the analysis of tumor-induced changes in mRNA expression of human metabolic genes in diverse cancer types, finding that the alterations are heterogeneous across different tumor types. Their analysis also suggests that expression changes of some metabolic genes may "enhance or mimic the effects of recurrent mutations in tumors," and that the various metabolic isoenzymes found to show tumor-specific changes hold promise as therapeutics targets.

Meanwhile, in Nature Methods, a group of international investigators describe a method, built around the concept of expression reversal of gene pairs, for identifying the determinants of cell fate. The team curated human expression data comprising 166 cell types and 2,602 transcription-regulating genes to develop the method, which enabled them to organize the cell types into their ontogenic lineage relationships. They used the approach to find genes in regulatory circuits that control neuronal fate, pluripotency, and blood cell differentiation.

New Face

Jeremy Farrar has been named as the new head of the Wellcome Trust, the charity says. Farrar, an infectious disease specialist, currently oversees the Wellcome Trust's Major Overseas Programme in Vietnam as well as the Oxford University Clinical Research Unit there.

Beginning October 1, he is to replace Mark Walport who left that post to become Britain's chief scientific adviser. The current interim director is Ted Bianco who had been heading up the agency's technology transfer office.

The University of Oxford's Colin Blakemore, who is also a former director of the Medical Research Council, tells the Nature News Blog that Farrar is a good fit for the Wellcome Trust, which has been increasing its support for research affecting the developing world.

"He may bring some new ways of working to the Trust, which would be more oriented toward public health and downstream research, applying tools we have today in addition to developing new tools," adds David Heymann, the chair of Public Health England's advisory board.