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Biodefense Boon Sweeps Proteomics As Researchers Seek $120M NIH Grants

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As the US government continues to rapidly expand its efforts to prepare for bioterrorist attacks, companies and researchers in the proteomics sector are in a prime position to rake in cash.

In the past year, US Congress has increased its budget for biodefense research by $1.5 billion. In response, the NIH and other governmental organizations have begun funding a slew of expensive and ambitious projects across the country aimed at developing the ability to rapidly diagnose and treat diseases such as anthrax, smallpox, and even ebola.

Proteomics, say researchers applying for some of these grants, will play a starring role in these efforts. “Proteomics is going to be extraordinarily important in all this … because however you do it, the proteins are everywhere,” said Bellur Prabhakar, head of the department of microbiology and immunology at the University of Illinois Chicago College of Medicine.

Prabhakar is a lead investigator in UIC’s bid for $120 million to construct one of two National Biocontainment Laboratories. This is the grand prize, following another round of grants of about half this amount, which will create Regional Centers of Excellence for Biodefense and Emerging Infectious Diseases — a still sizable award that will be given to four to six sites in the country. Only sites that win an RCE will be eligible to get NBL funding, so UIC is also vying for this designation, along with several other centers.

Although neither the RCEs nor the NBLs have yet been awarded, the NBL candidates have been narrowed down to four, according to researchers: UIC, the University of Texas Medical Branch, the University of California at Davis, and the Wadsworth Center in Albany, NY Winning programs will work with several institutions in their regions. All four candidates have a large proteomics component to their proposals, and all were site-visited by NIH reviewers over the past few weeks. A final decision for both awards will be reached in the early fall, according to NIH officials.

Race for the RCE

The RCE offering put out by the NIH specifically names proteomics as one of the “cross-cutting technologies” that it encourages institutions to include in their proposals. In addition, it states that the centers are expected to collaborate with pharma and biotech companies in order to “promote maximal use of the core facilities by a broad range of qualified scientists.”

The purposes of the RCE and the NBL are closely tied together. The RCE combines scientists from across the full spectrum of biological sciences and from several coope-rating institutions, who will take a wide variety of approaches to producing diagnostics, therapeutics, and new vaccines for potential agents of bioterrorism — chief among them so-called “category A” pathogens like anthrax, botulism, smallpox, and viral hemorrhagic fevers — as well as diseases like SARS about which there is little knowledge. The NBL will in turn provide biosafety level 2, 3, and 4 laboratories and other resources necessary to study the diseases. “There are very few places in the country where you can actually test new drugs and diagnostics on live pathogens that require containment at BSL level 3 or 4,” said David Gorenstein, professor of biological sciences and associate dean for research at UTMB School of Medicine, and would-be partner in UTMB’s RCE proteomics core.

To Luis Villarreal, the emphasis that the NIH is placing on proteomics for its biodefense initiatives makes a lot of sense. Villarreal is director of the Center for Virus Research at UC Irvine, and the head of the proteomics core in the University of California’s proposed RCE (the core would be centered at Irvine). “With bioterrorism, you’re dealing with two circumstances: the potential for a modified agent, modified by an unknown process, and also a new agent. So you really need a system in place that’s not tied into an existing knowledge set that’s applicable to something new,” Vil-larreal said. In response to such a need, Villarreal is working on the rapid translation and purification of entire viral and bacterial proteomes. These proteomes, he said, would provide the missing knowledge set. “If you have all the proteins in hand, you can figure out what to do about [a disease],” he said.

Other researchers agreed that pathogen studies present ample opportunities for those involved with proteomics, both academically and commercially. “Anything to do with virology and vectorology is a really good project for proteomics because you’re dealing with discrete pathogens and at least initially with pure cell lines and you can follow infectivity over time,” said Alexander Kurosky, director of UTMB’s proteomics center — established by the National Heart, Lung, and Blood Institute — and leader of the proteomics core in the UTMB RCE proposal (see PM 7-18-03).

If UTMB becomes an RCE, Gorenstein will have additional funding for his proteomics research on thioaptamers — aptamers that have chimeric part-sulfur backbones — in addition to $12 million in funding he has received in grants from the Defense Advanced Research Projects Agency, the Centers for Disease Control, and the Defense Threat Reduction Agency. The thioaptamer work, which uses these especially “sticky” aptamers to target cytokines, chemokines, and other proteins that are elevated as part of the immune response resulting from viral infection, would be applied to a wide range of pathogens that the center studies. The proteomics core of the RCE would be focused in general on providing “generic-type infrastructure for proteomics.”

Ciphergen Sees an Opportunity

Gorenstein is already collabor-ating with Ciphergen on biodefense research, baiting its SELDI chips with thioaptamers to fish for cytokines and other targets. Ciphergen is written into the RCE and NBL grants, with UTMB being allocated money to buy Ciphergen’s SELDI equipment, and Ciphergen getting money to build a laboratory to “take technology developed in Gorenstein’s lab and make it work in our environment.” If an RCE grant is awarded to UTMB, Gorenstein’s collaborations would be expanded to include several small biotech companies and “at least one major big pharma,” he said.

For Ciphergen and others, there is much to gain from the grants. “[With the RCE] short term we gain a significant chunk of revenue from them to buy a lot of hardware,” said Bill Williams, Ciphergen’s national sales manager for the US “Long term we’re going to share in the intellectual property,” he said. In terms of the NBL, the gains could be greater. “That’s a lot of money, and [for] whoever is making the decisions to buy proteomics technology at these centers — if we’re a major player as a proteomics company in what they decide to purchase, there’s a PR angle that will cross over into other market areas outside of biodefense,” Williams said.

According to Prabhakar, more companies, particularly those interested in drug discovery, should take a lesson from Ciphergen. “If I am one of those [proteomics] companies, even if I don’t see opportunities today or tomorrow, I would definitely establish very good relationships with NBLs, because if you are going to develop any product that needs to be tested, you are going to have to go into one of these places,” Prabhakar said. “The viability of a product will depend upon accessibility to the NBL and a very good relationship with the NBL people such as myself.”

The NBL is not the only opportunity to share in the biodefense boon.

“The growth in the government spending in proteomics for national defense, it’s huge,” Williams said. “And it’s going to be bigger going forward. It’s a big ocean.”

In September, the NIH will also announce five to 10 awards, in addition to awarding the RCEs and NBLs, for “Biodefense Proteomics Research Programs.” No funding cap was listed for the program.

— KAM

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