This story originally ran on Oct. 14 and has been updated to include estimated 2010 ARRA revenues to some life-tool vendors.
By Tony Fong
For the past eight years, researchers at the University of Arizona have been studying how environmental factors may cause asthma in young children.
They collected cord blood and tracked the children since birth to try to figure out whether factors such as early exposure to certain allergens may help protect them from developing asthma later in life.
While the researchers have done a number of genetic studies, they could reach no definitive conclusion. To get a clearer picture, they decided they needed to look at factors other than genetics, including the role proteins may play.
Around a year ago, they decided that the time was right to pursue the next stage of their research — the proteomics technology platforms had matured and the researchers were confident in their ability to find biomarkers in serum.
And when they applied for funding, they chose to apply for a Challenge Grant created by the National Institutes of Health under the American Recovery and Reinvestment Act of 2009, or the stimulus bill, rather than go through the usual National Institutes of Health R01 process.
"The advantage was the Challenge grant [solicitation] called for a lot of biomarker discovery [work]," said Serrine Lau, a professor at the school's College of Pharmacy. "Also, [NIH] did not [ask] you to have too much preliminary proteomics data."
As a result, she added, she felt that her chances of getting her project funded were better — a hunch that proved to be correct. Last week, UA announced that Lau and her collaborators at the university had been awarded a two-year, $937,302 ARRA grant from the NIH, one of 114 such grants awarded to proteomics researchers so far, in what has amounted to a bounty to the field.
The 114 awards for fiscal year 2009 total nearly $45 million. The figures are based on an analysis by ProteoMonitor of project titles in an NIH database, which was frozen as of Sept. 30, the end of the fiscal year.
The award number is just a fraction of the total number of ARRA grants awarded so far by NIH — 0.9 percent of the 12,788 ARRA grants, and 1 percent of the $4.4 billion in total ARRA funding. But the FY 2009 ARRA grants by themselves represent more than one-third of the total number of NIH grants awarded to proteomics research in FY 2008, when the number of grants shrunk by 8 percent to 317 and total dollar figures fell by 3 percent [See PM 02/05/09].
And as more ARRA grants are awarded during the coming months, the booty for the proteomics community will only grow.
The analysis was performed on NIH's Research Portfolio Online Reporting Tool, or RePORT, database, and was based on a survey of project names. Because some names may be vague or too broad, some proteomics projects may have been missed, and the number of proteomics research being supported with ARRA grants will almost certainly be higher than 114.
As a result, the figures are not a comprehensive list of all ARRA grants going to proteomics research.
Created as part of a broader initiative to jumpstart the economy, the ARRA grants also served to stimulate scientific work that, at the least, would have been delayed due to a lack of funding.
Lingjun Li, an associate professor of pharmaceutical sciences and chemistry at the University of Wisconsin-Madison School of Pharmacy, for example, received a $19,341 grant to hire an undergraduate student during the summer to improve the quantitation aspects of a method that she and her colleagues are developing for prion disease biomarkers.
That larger project is funded by the NIH at $360,000 for three years, but without the additional ARRA grant, she would not have been able to hire the undergraduate, she said. The larger NIH grant primarily pays for the salaries of one and a half graduate students, and though there are some mechanisms, including other NIH grants and National Science Foundation awards, that pay for undergraduate research support, her project did not qualify for them.
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"This really helped in speeding up the project," Li said, adding that she is awaiting word on an ARRA application to purchase a solariX FTMS from Bruker.
Indeed, since the NIH announced various funding opportunities resulting from the stimulus bill passed in February, major mass spec vendors have said they have been flooded by requests from researchers to help them write grant proposals using their technology. They also have aggressively wooed researchers with pitches to buy their technology and help them write their proposals.
And depending on the vendor, ARRA funding could translate to a major payday. According to estimates investment firm Macquarie Capital, Life Technologies, for example, is estimated to receive $112 million in NIH stimulus funding in 2010 alone, and Thermo Fisher Scientific could reap in $158 million in ARRA funding. It's unclear, though, how much would come from mass-spec sales.
Of the 114 grants awarded for FY 2009, 12 are for the purchase of a mass spec, totaling more than $5.4 million.
More ARRA grants targeted specifically to instrument purchases are expected to be announced later this year and in early 2010.
The most grants were awarded to projects that could be broadly defined as technology or method development. A total of 25 grants amounting to nearly $7.5 million were for projects ranging from the development of mass-spec based biomarker methods, to one given to Eva Birnbaum at Caldera Pharmaceuticals to create a novel X- ray translucent flow cell design for identifying protein interactions and characterizing post-translational modifications.
Biomarker identification- and validation-based projects also received a large portion of grants, 23 in all, totaling more than $9.4 million, including the largest proteomics ARRA grant given in FY 2009 [See chart this issue for the 10 largest proteomics-related ARRA grants].
That award, for a total of $4.8 million, including $3.2 million in FY 2009, which ended Sept. 30, will fund a team of investigators to create a library of anti-peptide antibodies to measure "defined" collections of proteins with high sensitivity and "absolute specificity" called the Human Proteome Detection and Quantitation initiative, or hPDQ [See PM 01/22/09].
According to the grant's abstract, the researchers will "assess [the] feasibility and scalability" of hPDQ. As part of that effort, they plan to generate a dataset of "unprecedented scale, configuring 800 novel assays to measure 400 human proteins," approximately 2 percent of all proteins in humans. They will then demonstrate the performance of the assays in a panel of about 50 "genomically well-characterized" breast cancer cell lines.
Also, 13 grants for more than $3.8 million were awarded to research that could be broadly categorized as functional proteomics. Research directed at bioinformatics and computational biology received 10 grants for almost $6.2 million.
Eighteen of the NIH's 27 institutes and centers handed out ARRA grants for proteomics. The National Center for Research Resources was the most generous, awarding more than $9.8 million spread among 19 grants, although the National Institute of General Medical Sciences gave out the most number of awards, 27, totaling $7.1 million.
The National Cancer Institute handed out 18 grants totaling $8.5 million.
The Money Trail
The ARRA grants will be used for a wide swath of research projects, including those that may have a harder time getting traditional NIH funding, such as the work being done by Lau at UA.
She and her collaborators will be using their grant to perform a proteomics study looking at children who have been exposed to dogs at an early age to determine whether such exposure protects them from developing asthma.
While their earlier studies suggested that changes in protein expression have a prophylactic effect, "the mechanisms behind what has changed molecularly were not known," said Lau, the principal investigator on the project.
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Their genetics-based work was also funded by the NIH. Lau said that she would have applied for an NIH R01 grant if the ARRA grants didn't exist, but the nature of the ARRA Challenge grants improved her chances of success.
While she and her collaborators had amassed a mountain of genetic data from their longitudinal work, they had little data to support a new proteomics approach.
"For R01s, they would probably want you to have all aspects and each specific aims, and the reviewers' approaches to this is very different in terms of looking at novel ideas. If you will, these are kind of unconventional" research projects that are being funded, Lau said.
Many of the recipients of this round of awards include prominent researchers in the field such as Steve Carr at the Broad Institute; Fred Regnier at Purdue University; and Daniel Liebler at Vanderbilt University.
Leroy Hood, co-founder of the Institute for Systems Biology, also is listed as a principal investigator for a grant to "develop and provide a proteotypic peptide fragmentation database, of at least 4 peptides per human protein-coding gene, with verified rapid and accurate MRM based mass spectrometric assays to unambiguously identify and quantify any protein of the human proteome in a multitude of samples," according to the grant abstract.
Richard Smith at the Pacific Northwest National Laboratory received two grants to further develop a new proteomics platform combining ion mobility separation with time-of-flight mass spectrometry for the detection and quantitation of lower-abundance peptides and proteins in biological fluids.
The development of the platform has been funded mainly with NCI money, which provided additional funding under ARRA. The new ARRA funding includes a grant from the NCRR, as well.
The new NCI funds will allow Smith and his colleagues to build out the platform and to evaluate additional samples "to look deeper into the proteome for some standard samples and to further develop the mass spectrometry end of the platform," to sequence peptides more effectively, he said.
The NCRR grant will be used to build two new versions of the platform and create a collaborative study with the clinical translational center at the Oregon Health Sciences University to carry out a large-scale proteomics study.
The original funding helped to develop the technology but the ARRA funding will help bring it to point where it can be used and help move the platform to the NCRR center at PNNL.
"Our NCRR Center hasn't really had the platform in the center, so it's allowing the infrastructure of the center to be expanded to include that instrumentation," Smith said. "It's always difficult to build infrastructure. The main thing that this is doing is speeding up the pace of research significantly.
"I think that we would get to this point [eventually], but it would take several years longer, and this is allowing us to get to a stage where we can do the large-scale population proteomics several years earlier at a minimum," he added.
The institution that received the most funding was the Fred Hutchinson Cancer Research Center, with $3.2 million, where clinical research associate Amanda Paulovich is listed as one of the principal investigators on the hPDQ project, though the funding is actually being divvied among several institutions involved in the research.
Researchers from the University of Washington received six grants, the most awarded to any one institute, totaling $1.85 million, while Vanderbilt researchers received five grants totaling almost $2.1 million.