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NIAID Awards $12.3M for Dx-Focused Translational Research Centers at Columbia, Harvard

NEW YORK (GenomeWeb News) – Harvard Medical School and Columbia University have both received grants from the National Institute of Allergy and Infectious Diseases, totaling $12.3 million this year, to create translational research centers to develop molecular diagnostics technologies.

Funded under NIAID's Centers of Excellence for Translational Research program, the grants will provide $6.3 million to Columbia and $6 million to HMS this year.

Columbia will use its CETR award to create a Center for Research in Diagnostics and Discovery, which will involve researchers at multiple institutions working together to develop, validate, and implement multiplex tools and predictive strategies for detecting novel pathogens. The researchers also will aim to identify host factors that may influence disease susceptibility or predict the effectiveness of drugs or vaccines.

HMS will use a CETR grant to launch a center focused on developing a molecular diagnostic test for Mycobacterium tuberculosis. This center is focused on discovering new biomarkers of resistance, identifying new clinical sampling strategies, and developing a sensitive microarray-based diagnostic test.

Ian Lipkin, director of the Center for Infection and Immunity at Columbia's Mailman School of Public Health, will also direct the new Columbia CRDD, which could receive a total of $31 million over the full term of the award.

Lipkin told GenomeWeb Daily News today that NIAID's CETR funding was created to spur development of drugs, diagnostics, and vaccines, and to detect microorganisms that may be health threats. The Columbia center's efforts will be aimed at pursuing several methods and tools for swiftly and accurately recognizing those potentially dangerous microorganisms. The studies will include multiple partners and approaches that will range from genomics and systems biology to bioengineering.

"We are using a field-able microarray that will not require amplification, either isothermal or PCR-based, but will detect binding events in fluid samples, extracts, and tissues," Lipkin said of one project. He said this effort will incorporate carbon nanotubes to recognize genetic material from oligonucleotides, and is based on probe libraries already housed at Columbia.

Another study is a systems biology project that will use molecular and proteomic tools to assess risk and response. This study will focus on host response and will use microarray RNA-Seq analyses in a collaboration with the New York State Department of Health, the New York City Department of Health, the EcoHealth Alliance, and other partners, Lipkin told GWDN.

Through these collaborations, he said, the center will have access to samples that it will analyze using proteomic and transcriptomic methods to develop tools to help physicians make treatment decisions about which patients should be treated with which drugs, as well as identify which patients may be susceptible to severe disease or may recover without treatment.

In another project, the CRDD and its partners are using oligonucleotides to improve the sensitivity for detection of rare molecules that will be run through high-throughput sequencing.

Lipkin also said he is leading an effort through a partnership with NimbleGen to generate comprehensive libraries of millions of peptides that will make it possible to recognize previous exposures to infectious agents. "Our hope is that we will be able to recognize who has been vaccinated and will be protected, [and] who has previously been exposed to a related infectious agent and may be protected, so that we can begin to use this for designating first responders who might go into a region where there is a potential risk."

All of these projects are integrated together, Lipkin said, and include investigators from Columbia, Stanford University, The University of North Carolina at Chapel Hill, and the other partnering organizations.

The HMS center, led by Professor Megan Murray, will pursue four research projects with the goal of improving the diagnosis of drug-resistant TB, particularly in children.

"The TB epidemic is still fueled by the fact that people are diagnosed relatively late in the course of their disease and a lot of transmission happens before diagnosis," Murray, who also is director of research at Partners in Health, said in a statement today. "There's no single therapy for TB, so there's a big need to know which drugs people are resistant to."

In one project, the Harvard center will build on work that used whole-genome sequencing to identify genetic mutations linked to drug resistance. Researchers will study roughly 1,500 TB strains from an ongoing study in Peru to characterize the mechanisms of drug resistance and quantitative drug resistance, or the specific amount of a drug to which a strain becomes resistant.

The center also will partner with Akonni Biosystems to develop a diagnostic tool to be used in the field. Akonni will optimize a microarray to test for mutations associated with TB drug resistance.

In another project, the center will use techniques developed for genomics studies of Neanderthal samples to capture fragments of genetic material from TB found in children to try to develop a blood or urine-based test. Such a test would be an improvement over the standard sputum test because children have difficulty coughing up useful samples.

"In the Neanderthal project, the challenge has been to take very degraded mammalian DNA mixed with bacterial DNA," Murray said. "In our case, we've got the other problem: We try to pull microbial DNA mixed with human DNA in urine. Can we sequence that?"

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