BIOPHOTONICS DEVELOPMENT FUNDING/EPIGENETICS/OPTICAL SENSING: Driving biophotonics innovation: NIH New Innovator Award - Part 1

With this article, BioOptics World begins a periodic look at the impact on biophotonics of the NIH Director's Awards—a portfolio that supports high-risk, high-reward research. First up, the New Innovator Awards, aimed at early-stage investigators who have not previously received NIH grants.

By Susan M. Reiss

In an instant, a beam of light from a whispering gallery mode resonator flicks through a stream of serum DNA. Analysis of this interaction could help epigenetics researchers understand why cancer, in particular ovarian cancer, forms (see Fig. 1). This simple, yet elegant, coupling is fast becoming reality, thanks to a grant from the National Institutes of Health's (NIH's) New Innovator Award (NIA) program, established in 2007 to support early-stage investigators who have not already benefitted from NIH funding.

As the centerpiece of the sensor platform, the whispering gallery mode resonator will interrogate streams of molecules
FIGURE 1. As the centerpiece of the sensor platform, the whispering gallery mode resonator will interrogate streams of molecules.

In just over a year, Andrea Armani, a University of Southern California engineering professor, who received a grant in the 2010 NIA competition, has invented a new sensing modality, discovered a way to recycle the sensor platform, and is discussing ways to scale up production to make the platform available to researchers across the country. What's unusual about this trajectory is that when she applied for the five-year, $2.5 million award, Armani only had an idea—no device and no data.

Genesis of an optical detector

During a retreat for medical school and engineering faculty, Armani listened as a group of epigeneticists described the barriers to studying the fundamental causes of cancer. To advance their work, they needed a tool that would detect and analyze the presence of methyl groups—magnet-like molecules that attach to and silence DNA. By determining why these molecules attach to DNA, the epigeneticists theorized that it may be possible to proactively clean up the DNA to reduce or eliminate the impact of methyl groups in cancer formation.

Intrigued, Armani came up with the idea of an optical sensor, based on a rare-earth doped optical cavity, to detect and quantify methyl groups (see Fig. 2). But to build the laser, Armani needed about $200,000 worth of equipment. Her one shot at securing funding was NIH. "This idea wasn't going to get funded by any other agency," says Armani, who had never before received an NIH grant. And although engineers "typically don't fare well," she applied.

The resonator-and an optical fiber-rendered by the freeware multi-platform ray-tracing package PovRay
FIGURE 2. The resonator-and an optical fiber-rendered by the freeware multi-platform ray-tracing package PovRay.

"NIH put a lot of faith in me and the idea," says Armani. Accepting proposals without experimental results is a unique feature of the NIA application process. An independent evaluation of the NIA program completed in 2011 shows that while 80% of applicants provide early results, this information "did not improve the odds of being awarded an NIA."1

Unlike typical grant programs which usually involve lengthy proposals and a single review phase, the NIA process included a 10-page application and a multi-phase review process that included two sets of reviewers, ranking by NIH program officers and final oversight by the director's office. Reviewers scored applicants on three criteria: Scientific problem, innovativeness, and investigator qualifications. Innovativeness is the biggest predictor of whether an applicant makes it to the final round.1

With most research grants, investigators "often have to choose between equipment and people," but the term and size of Armani's award and its lump sum payout allowed her to buy equipment and hire students who will work on the project until its completion. The limited paperwork involved—no annual budgets are required—also allows Armani to spend more time in the lab. For three months last summer, Armani moved her computer into her lab and worked alongside her students, an opportunity she describes as "very freeing."

Tracking to commercialization

Driving innovation from idea to commercialization is another benefit of the NIA program. Although the awards themselves are relatively new, early recipients are beginning to move their ideas to the marketplace. 2007 NIA recipient Derek Toomre, a cell biologist at Yale University's School of Medicine, not only built a new microscope and illumination system, but patented the design. On December 12, 2011, Applied Precision Inc., a GE Healthcare company, announced that it had licensed the "Ring-TIRF microscopy" technology from Yale. According to Paul Goodwin, director of advanced applications at Applied Precision, "This is the first major advancement in TIRF microscopy to come about in several years."

The new illumination system eliminates the usual interference patterns and coma artifacts associated with total internal reflection fluorescent (TIRF) microscopes. It also allows researchers to track specific molecules as they interact with their environment at various penetration depths and provide 3-D imaging near the surface of a cell.

"The grant made a tremendous difference and literally allowed me to realize my vision and see if it would work as proposed," says Toomre. Validating the concept of novel illumination systems for TIRF microscopy allowed Toomre and coworkers to build, refine, and ultimately license the instrument.

"It's one thing to make a one-off, but if you can make a device that is useful and translate it to many labs, then it can have a larger impact," he says.

Funds for out-of-the-box thinking

Although NIH began supporting high-risk, high-reward projects with its Pioneer Awards in 2004, passage of the NIH Reform Act of 2006 allowed NIH to expand its support of truly innovative research. The legislation established the Director's Common Fund "to support high-risk, high-reward projects like the Pioneers and to support large, collaborative, and transformative projects which cut across the missions of multiple NIH Institutes and Centers," says James Anderson, director of NIH's Division of Program Coordination, Planning, and Strategic Initiatives. Common Fund programs provide an alternative to standard grants which tend toward conservative research. "These [traditional] programs are not a negative, but they can limit out-of-the-box ideas," he says.

Congressional and NIH program support of the Common Fund portfolio signaled a new direction in federal science funding. "By the nature of the program, we are not funding incremental science. These projects have the potential to move science faster and in larger steps [than conventional projects]," he says.

Nearly a decade and $1 billion later, the "experiments," as Anderson refers to the expanding grant portfolio, continue to make an impact. In addition to the Pioneer and New Innovator Awards, NIH also sponsors the Transformative Research Awards for interdisciplinary teams (established in 2009) and its newest award program—initiated in October 2010—the Early Independence Award (http://commonfund.nih.gov/early independence) aimed at researchers who have just completed an M.D. or Ph.D. Over 400 researchers have received grants from these four programs.

REFERENCE

1. Institute for Defense Analyses, Science and Technology Policy Institute, Process Evaluation of the National Institutes of Health Director's New Innovator Award Program: FY 2007-2009, Washington, DC; http://commonfund.nih.gov/pdf/NIA_PE.pdf (May 2011).

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