Contact:
Min H. Song, Ph.D.
Technology Development Branch
Cancer Diagnosis Program
Division of Cancer Treatment and Diagnosis, NCI
Telephone: (301) 402-4185
E-Mail: ms425z@nih.gov
Objective of the Project:
This Request for Applications is to support the development of innovative or substantially improved technologies for both a comprehensive identification and a sensitive, efficient, and reproducible, quantitative analysis of all expressed and modified proteins in human tumor specimens. The approaches proposed should take into account the current needs to identify and quantitate a broad range of proteins including proteins present in low abundance and proteins that are membrane-associated or not readily soluble. The approaches should also be sensitive enough to detect modest changes in protein concentrations.
Description of the Project:
Technologies for the comprehensive evaluation of DNA and RNA alterations in tumors are rapidly being developed, but development of comparable technologies for the evaluation of protein expression in human tumor specimens has been slower due to the inherent difficulties of analyzing complex mixtures of proteins. Major technical challenges in protein profiling include the quantitation of hydrophobic, cell membrane-bound proteins and the improvement in detection sensitivity for measurement of very low-abundance proteins. This initiative will invite investigators to propose the development of technologies for both a comprehensive identification and a sensitive quantitation of proteins present in human tumor specimens. They may propose to further identify proteins by linking protein data to mRNA expression databases, peptide mapping databases, three-dimensional protein structure databases, and/or protein function databases. Individual proteins may be further characterized by amino acid sequence, molecular weight, post-translational modifications, or proteolytic peptide maps. Investigators may also choose to identify and quantitate the proteins present in subcellular compartments (membranes, nuclei, mitochondria, microsomes, and cytoplasm) of human tissues. Knowledge of both identities and relative abundance of all proteins in tumors will greatly enhance our understanding of molecular pathways underlying the development of cancer, and potentially improve clinical decisions regarding diagnosis, prognosis, and treatment of cancer patients. In addition, comprehensive, quantitative protein profiles of tumors at various stages of cancer development could ultimately permit the identification of multiple tumor-specific markers that will aid in target identification and diagnostics.