Tools for Cell Line Identification (SBIR [R43/R44])
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The official link for this solicitation is: http://grants.nih.gov/grants/guide/pa-files/PA-16-186.html
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Tools for Cell Line Identification (SBIR [R43/R44])
This Funding Opportunity Announcement (FOA) is intended to address the problem of misidentified cell lines. Many advances in biomedical science have arisen from studies of cultured cell lines, which are widely used for basic research on cell function, as models for disease, and for drug screening. In most of this research, correct identification of the cell lines used is necessary to replicate experiments. In addition, in a majority of the projects the cell lines used were chosen because they are predicated to recapitulate biologically important features of the tissue and/or tumor of origin, for example, driver mutations, expression patterns, and functional correlates of the differentiated state of the original tissue.
Cell line origins are documented by chain of custody (a continuous chronological record documenting their source, transfer, analysis, and disposition). However, cell lines in culture are prone to contamination by foreign cells, which may rapidly displace the original cells. The identity of cultured cells should be routinely verified, but a majority of laboratories do not monitor the identity of their cell lines, and many cell lines are misidentified. Analyses of cells submitted to major repositories such as the ATCC (American Type Culture Collection) and the DSMZ (Deutsche Sammlung von Mikroorganismen und Zellkulturen) have found that 15-40% of cell lines submitted by investigators are misidentified, i.e., they have a tissue or species of origin that differs from the one reported. Similar frequencies of misidentification have been reported by research laboratories that have examined cell line collections.
If we consider cell lines that have been displaced by known cell lines (estimated at 15-30%), cell lines that were incorrectly identified when they were first cultured (unknown), cell lines that have been displaced by unknown cell types (unknown), and cell lines recently mislabeled or contaminated by end users (unknown), the overall frequency of misidentification of cell lines is likely to be high enough to warrant routine surveillance. Only the first and fourth of these scenarios can be detected with current technologies.
The costs, effort, and time required to confirm the identity of cell lines has been a barrier to adoption of cell line identification as a routine quality control measure. The purpose of this FOA is to stimulate the development of reliable, rapid, cost effective, and easy to use tools that will assist researchers in confirming the identity of the cells that they use in their work. Ideally, these new techniques could be readily adopted for use in individual research laboratories.
Current technologies for identifying cultured cells are limited, and their cost is a barrier for small scale use. This FOA will support SBIR projects to improve existing technologies and/or develop new methods for the definitive identification of cultured cells. Topics include, but are not limited to:
- Development of novel, cost effective, and reliable technologies that allow researchers to easily identify cell lines, including non-human cell lines, used in their laboratories. These new methods may be based on genetic, epigenetic, transcriptomic, proteomic, metabolomic, or sequence-based profiling of cells.
- Modification of existing technologies for cell identification, such as STR and SNP profiling, that improve reliability, reduce costs, and/or facilitate the type of frequent, small scale use prevalent in individual laboratories.
- Methods for detecting contaminating cells that are present in cultures at low levels (<10%).
- Methods for assessing the origins of cell lines where original biopsy tissue is not available. The goal is to identify cell lines that were incorrectly identified or contaminated when they were first cultured, or have been displaced by unknown cell types.
- Tools for (i) characterizing the genetic divergence of cell lines from the progenitor line and from other subtypes, (ii) estimating generations (passage number) from genetic distances and deriving lineage trees, or (iii) rapid karyotyping.
- Methods for distinguishing between cell lines derived from individuals of the same inbred line, e.g. C57BL/6.
- Methods for distinguishing between cell lines based on their tissue of origin or tumor type.
- Methods for distinguishing between cell lines based on phenotype (including but not limited to morphology), signaling network activities, gene expression profiling, or other characteristics.
- Methods for verifying the sex of the donor after the Y chromosome has undergone re-arrangement and/or become unstable.
- Computational tools directly relevant to cell identification.
- Development, evaluation, and dissemination of robust protocols for handling tissue and cells at all stages from bedside to bench.
- Development, evaluation, and dissemination of standards and/or training materials that detail good laboratory practices to be followed when using cultured cells.
Applications for support of research and development of particular types of complex technologies that require funding levels and durations beyond those reflected in standard SBIR guidelines are encouraged, as are multi-PD/PI applications, including multi-PD/PI applications that arise from academic-industrial partnerships.
It is anticipated that many of these tools will prove useful in the identification of embryonic stem cells, induced pluripotent stem cells, and primary cells as well as in the identification of immortalized cell lines.
National Institute of Dental and Craniofacial Research (NIDCR)
NIDCR has a strong interest in supporting the development of tools that have the potential to be of use in both cell line authentication and the identification of mesenchymal stem cells.
Office of Research on Women's Health (ORWH)
ORWH has a strong interest in supporting the development of methods that can quickly and accurately determine the sex of immortalized cell lines, stem cells, and primary cells.
Office of Research Infrastructure Programs (ORIP)
ORIP is interested in supporting the development of novel methods and tool for authentication and identification of cell lines, primary cells and stem cells from animal models.
Visit the websites of the remaining participating NIH institutes and centers for information about their missions and general areas of interest.
See Section VIII. Other Information for award authorities and regulations.