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Publication Date - 4/28/2000

11. NIH/NCI - Improving DNA, RNA, and Protein Availability in Fixed Tissue

The National Cancer Institute (NCI) invites applications for research in improving DNA, RNA, and protein availability in fixed tissues. The application of many molecular technologies currently requires access to fresh or frozen tissue specimens because of the limited ability to extract sufficient high quality RNA or protein from fixed tissue. Clinical application of potentially useful molecular technologies is also hampered by fixation methods that fail to conserve the structure of nucleic acids and proteins in tissues. Clinical application of potentially useful molecular technologies is also hampered by fixation methods that fail to conserve the structure of nucleic acids and proteins in tissues.

A better understanding of the physical and chemical basis of tissue preservation is vital for the rational development of new fixation methodologies. This initiative would encourage

• research to develop new fixation methods to better preserve macromolecules, and
• methods to reverse the effects of formalin fixation to make nucleic acids and proteins more readily accessible in archived specimens.

Some examples of the types of studies that could be supported by this PA include but are not limited to the following:

• studies to better understand the basic mechanisms of fixation, with the ultimate goal of developing practical approaches to improve the availability of high quality DNA, RNA or protein from fixed tissue;
• studies to understand the impact of tissue handling during fixation; e.g.,. evaluate the effects of heat, oxygen, diffusion rates and the penetration of fixatives into tissues and identify the major factors that affect the stability of macromolecules;
• studies to determine the importance of cross-linking in the stable morphological preservation of formalin fixed tissue;
• studies of methods to disrupt cross-links to free DNA, RNA and proteins;
• studies of the usefulness of enzyme inhibitors to stabilize nucleic acids and proteins in fixed tissues;
• studies to evaluate the impact of current embedding procedures on the integrity of macromolecules in fixed tissue.

This PA will use the NIH exploratory/developmental R21 grant mechanism. This mechanism is utilized for pilot or feasibility studies to support exploratory research that may lead to innovative advances in science. The total project period for an application submitted in response to this PA may not exceed two years. Budgets must be requested in $25,000 increments. The total direct costs requested may not exceed $100,000. These grants are non-renewable.

A Letter of Intent to Apply is requested to arrive at the NCI on or before JUNE 14, 2000 and FEBRUARY 9, 2001. Applications are due at the NIH Center for Scientific Review on or before JULY 19, 2000 and MARCH 16, 2001.