NIGMS Makes First Awards for "High Risk/High Impact" Studies

Release Date:
Alisa Zapp Machalek, NIGMS

In an effort to encourage scientists to submit grant applications for highly innovative--but also highly risky--research studies, the National Institute of General Medical Sciences (NIGMS) issued a call last March for "high risk/high impact" proposals. Now, NIGMS has awarded $2 million to support 20 grants from the first round of applications.

"These awards will provide an avenue for scientists to pursue innovative hypotheses that, if confirmed, would have a substantial impact on current thinking or approaches," said Marvin Cassman, Ph.D., director of NIGMS.

Four of the newly awarded grants are described below. The principal investigator's name and institution are in parentheses.

  • A study examining whether hydrogen sulfide (H 2S)--a toxic gas that smells like rotten eggs--regulates functions in the brain, internal organs, and blood vessels. Like the gas nitric oxide, which helps regulate neural function, blood pressure, and many other processes, H 2S is produced in the brain and in involuntary smooth muscle. An understanding of the role of H 2S in these tissues may have many therapeutic applications, for example, in the control of blood pressure. (Hideo Kimura, Ph.D., Salk Institute for Biological Studies, San Diego, CA)

  • An investigation of how tissues and organs grow to specific sizes and proportions. The researcher proposes that tissue size and shape are controlled by a competition between cell division and cell death. He plans to study fruit flies--which utilize many of the same genetic pathways as humans--to identify genes that maintain the balance between cell division and cell death. The work promises to provide a basic understanding not only of growing tissue, but also of developmental disorders, cancer, and neurodegenerative diseases. (Nicholas E. Baker, Ph.D., Albert Einstein College of Medicine, Bronx, NY)

  • A method to grow cultured laboratory cells into an "artificial placenta" that may reveal how pharmaceuticals given to pregnant women affect their fetuses in utero. Currently, there is no good way to determine the concentration of drugs that cross the placenta into a fetus. The researchers plan first to study the effects of AZT, a drug used by large numbers of HIV-infected women to minimize the risk of transmitting the virus to their developing babies. (Douglas A. Kniss, Ph.D., Ohio State University, Columbus)

  • A new genetic strategy to control specific brain receptors (GABA type A) to enhance the action of general anesthetics, antianxiety drugs, and anticonvulsant drugs. Normally, scientists targeting brain cells develop drug molecules that interact with receptors to produce a desired response. Modifying brain receptors directly is a novel, and potentially more specific and effective, therapeutic strategy. (Jay Yang, Ph.D., University of Rochester Medical Center, Rochester, NY)

NIGMS received 102 applications in the first round--an enthusiastic response for a new initiative. "While some of these first applications were not appropriate for the program, others were "right-on," according to James Anderson, Ph.D., the NIGMS program director who spearheaded the initiative. "We expect that as word spreads about what we're looking for, more and more people will find it in their interest to apply," he said.

The program supports research that is both "high impact" and "high risk"--high impact because it has the potential for ground-breaking, precedent-setting significance, and high risk because it either lacks sufficient preliminary data to ensure its feasibility, or involves using a new model system or technique.

The research must fall within the confines of NIGMS' mission, which is broad-based, fundamental research in areas such as cell biology, biophysics, genetics, developmental biology, pharmacology, biochemistry, bioengineering, anesthesiology, trauma, and burn injury.

The grants are awarded for up to two years and up to $70,000 per year in direct costs. They are non-renewable, but may be incorporated into a subsequent application for a regular research grant. Application deadlines are February 1, June 1, and October 1.

For further information see All of the grants awarded under the new initiative are listed below.

To arrange an interview with Dr. Cassman or Dr. Anderson, call the NIGMS Office of Communications and Public Liaison at (301) 496-7301.

"High Risk/High Impact" Grant Awards--March 31, 1998

"Genes Mediating Cell Competition and Survival," Nicholas E. Baker, Ph.D., Albert Einstein College of Medicine, Bronx, NY.

" In vivo Chemiluminescent Activation of Photosensitizers," Susan L. Carpenter, Ph.D., Iowa State University, Ames.

"Extrinsic Modulation of Protein-Ligand Recognition," Ashutosh Chilkoti, Ph.D., Duke University, Durham, NC.

"Assay System for Evaluating Cellular Antisense Delivery," Moo J. Cho, Ph.D., University of North Carolina, Chapel Hill.

"Bacterial Host/Vector Expression of Membrane Protein," Mary Collins, Ph.D., University of Wisconsin-Milwaukee.

" In situ, Remotely Interrogatable Magnetochemical Sensors," Craig Grimes, Ph.D., University of Kentucky, Lexington.

"Chemical Shift of H 2O as Index of Vascular PO 2," Thomas Jue, Ph.D., University of California, Davis.

"Physiological Function of Endogenous Hydrogen Sulfide," Hideo Kimura, Ph.D., Salk Institute for Biological Studies, San Diego, CA.

"Artificial Placenta for in vitro Drug Screening," Douglas A. Kniss, Ph.D., Ohio State University, Columbus.

"Regulation of Apoptosis by NOS," Joan B. Mannick, M.D., Dana Farber Cancer Institute, Boston, MA.

"Virus DNA Targeting Mechanism--The Target," Gerd G. Maul, Ph.D., The Wistar Institute, Philadelphia, PA.

"Tolerance in Non-Clonal Immune Systems," David Nemazee, Ph.D., National Jewish Medical and Research Center, Denver, CO.

"Testing a New Model of CO 2 Transport in the Blood," Henry D. Prange, Ph.D., Indiana University, Bloomington.

"Ultimate Signal-to-Noise in Low-Frequency EPR," George A. Rinard, Ph.D., University of Denver, CO.

" In vivo Gene Targeting and Gene Therapy in Zebrafish," Michael C. Schmale, Ph.D., University of Miami, FL.

"Molecular Cytology of Mitochondrial DNA Replication," Richard M. Showman, Ph.D., University of South Carolina, Columbia.

"Tools for Genetic Mapping in Yeast," David J. Stillman, Ph.D., University of Utah, Salt Lake City.

"Novel Cell Labeling for in vivo MRI Studies," Daniel Turnbull, Ph.D., New York University Medical Center, New York, NY.

" In vivo Receptor Binding of Biopharmaceuticals," Peter Veng-Pedersen, Ph.D., University of Iowa, Iowa City.

"Adenovirus Mediated Neuronal GABAA Receptor Engineering," Jay Yang, Ph.D., University of Rochester Medical Center, Rochester, NY.