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US Army Medical Research Command Adds Bioinformatics to its R&D Arsenal

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Now Recruiting: the US Army Medical Research and Materiel Command (USA-MRMC), which serves as the Army’s primary medical R&D resource and plays an important role in keeping US soldiers healthy in combat situations. Faced with an influx of genomics and proteomics technology in its research labs — and additional pressure to deliver field-ready products — the MRMC is actively bolstering its bioinformatics capabilities.

Two years ago, the MRMC began building what it calls its Bioinformatics Cell to “serve as the Army’s in-house expertise in bioinformatics to optimize intramural as well as extramural activities,” said Jaques Reifman, director of bioinformatics at the MRMC. Reifman is now recruiting new members for the team, which provides bioinformatics support and training for researchers spread across six major laboratories: the Walter Reed Army Institute of Research; the US Army Medical Research Institute of Infectious Diseases; the US Army Medical Research Institute of Chemical Defense; the US Army Institute of Surgical Research; the US Army Research Institute of Environmental Medicine; and the US Army Aeromedical Research Laboratory. R&D activities are structured around four research areas: military infectious diseases; combat casualty care; military operational medicine; and medical, chemical, and biological defense.

The six-member Bioinformatics Cell, based in the MRMC’s Fort Detrick, Md., headquarters, is unique among the Army’s R&D organizations, Reifman said. A number of Army R&D groups outside the MRMC are dabbling in genomics and proteomics with the support of a single bioinformatics expert, but the MRMC’s medical focus and broad research agenda demanded a centralized bioinformatics group, he said. “If you look across the four research areas and the six laboratories, there’s one research area that really cuts across them all — genomics and proteomics. The rationale for putting together the Bioinformatics Cell was that we can put a group together that can cut across the research areas and the laboratories and also … address the paucity of researchers with both life science and computer science background,” Reifman said.

The Bioinformatics Cell has three key responsibilities, Reifman said. Its primary activity is to collaborate with the principal investigators in the research labs on the analysis of genomic data — primarily from microarray experiments. In addition, because the activities of the Bioinformatics Cell cut across the entire command, the MRMC draws on this unique perspective for strategic advice for aligning its R&D resources with new genomics technology, Reifman said. Finally, the Cell plays a role in the MRMC’s disbursement of funds added to the DoD budget under the Congressional Special Interest Medical Program. Since 1990, the MRMC has managed over 100 CSI programs totaling over $3 billion. Reifman estimated that around $600 million in CSI funding flows through the MRMC annually to support extramural medical R&D of interest to the Army. The Bioinformatics Cell provides expertise “to guide and shape the research that is being done from these extramural activities so that the army benefits from it,” Reifman said.

Military Microarrays

Without a doubt, the Bioinformatics Cell’s primary research focus is in microarray analysis. Reifman estimated that around 30 research groups across the MRMC’s six labs currently rely on DNA microarray experiments for a broad range of studies. In military infectious diseases, for example, researchers are using microarrays to study differentially expressed genes in patients infected with malaria or dengue fever to learn more about the timelines of the diseases. In combat casualty care, researchers are focusing on hemorrhage control — the leading cause of casualties in the battlefield — by studying genes that are differentially regulated in bleeding in rats. In military operational medicine, researchers are studying the response of soldiers to extreme environmental conditions by exposing cell lines to extreme temperatures and then performing microarray analysis to determine which genes are associated with heat and cold shock.

Reifman said that PIs at the research labs often opt for off-the-shelf gene expression analysis software to analyze their results, but there are many cases where the available software is inadequate and the Bioinformatics Cell needs to modify existing tools or develop something new. One challenge, Reifman said, is the MRMC’s reliance on animal models for much of its research. “[We can’t] expose somebody to extreme environmental conditions, or to a pathogen, or bleed someone to death to collect data, so we rely very heavily on animal models. We’re not like the NCI that can line up 500 patients and start collecting data from the human model that they’re actually trying to cure…We have to come up with ways in which we can map data from animals to humans,” he said.

As a first step, the Bioinformatics Cell has extended some available gene expression analysis tools, such as Wayne University’s Onto-Express, to work on the animal models it uses. In other cases, researchers are making do with what is available. “There’s a lab here that infects non-human primates with pathogens. Then they do DNA microarray analysis, but there’s no DNA microarray chip for non-human primates, so they use the human chip. That raises the question of what difference would it make if we had the genes there from the monkeys,” Reifman said.

The Bioinformatics Cell, however, doesn’t concentrate solely on microarray analysis. For example, Reifman said he is collaborating with Nela Zavaljevski and Fred Stevens of Argonne National Lab to develop a machine-learning algorithm to identify the key amino acids that characterize protein function.

The group also hosts training workshops and courses in bioinformatics methods for MRMC researchers, and in November, it will play host to an even broader audience. when it hosts the first US Army Workshop in Bioinformatics — an invitation-only three-day workshop for around 150 participants drawn mainly from military and government research labs.

Launched with an undisclosed amount of “seed money” from the MRMC budget, the Bioinformatics Cell will seek future funding in joint proposals with MRMC PIs, Reifman said. The group is also in the process of putting a dedicated bioinformatics facility in place, he said, but did not provide further details.

— BT

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