NASA SBIR 2008 Solicitation


PROPOSAL NUMBER: 08-1 X13.02-9726
SUBTOPIC TITLE: Technology/Technique for Imaging Radiation Damage at the Cellular Level
PROPOSAL TITLE: Chromatid Painting for Chromosomal Inversion Detection

SMALL BUSINESS CONCERN (Firm Name, Mail Address, City/State/Zip, Phone)
KromaTiD Inc.
515 E. Laurel St
Fort Collins, CO 80524 - 3151
(505) 662-5626

PRINCIPAL INVESTIGATOR/PROJECT MANAGER (Name, E-mail, Mail Address, City/State/Zip, Phone)
Edwin Goodwin
515 E. Laurel St
Fort Collins, CO 80524 - 3151
(505) 662-5626

Expected Technology Readiness Level (TRL) upon completion of contract: 4 to 5

TECHNICAL ABSTRACT (Limit 2000 characters, approximately 200 words)
We propose a novel approach to the detection of chromosomal inversions. Transmissible chromosome aberrations (translocations and inversions) have profound genetic effects, such as disrupting regulatory sequences that control gene expression, or creating genetic chimeras. These chromosome aberrations play a causative role in cancer, and they are induced by radiation. As such, chromosome aberrations are relevant to three NASA needs, biodosimetry, analysis of astronaut lymphocytes for cumulative radiation damage, and space radiation risk modeling. Of all structural chromosomal anomalies, inversions – a reversal of orientation of material within a chromosome – are the most difficult to detect. This is especially true of small inversions, most of which are invisible to all current cytogenetic techniques. Yet small inversions are likely the most transmissible (nonlethal) form of chromosomal damage, so they persist, a feature which lends credence to their use in retrospective biodosimetry. This Phase 1 project is intended to provide a proof-of-principle demonstration of a new method of molecular cytogenetics that will permit highly sensitive inversion detection. The project will help us to perfect our bioinformatics strategy for probe design, optimize probe labeling reactions, refine hybridization conditions, and establish a procedure for cost analysis. In Phase 2, we will scale-up probe production to make whole chromosome analysis possible. This next step, although conceptually simple, relies entirely on the processes devised and tested in Phase 1. Moreover efficient, cost-effective probe-making will be essential to commercialization (Phase 3). The technology readiness level at the end of the Phase 1 contract is expected to be 4-5, i.e. validated in laboratory and relevant environments.

POTENTIAL NASA COMMERCIAL APPLICATIONS (Limit 1500 characters, approximately 150 words)
Three applications of interest to NASA are: 1) Biodosimetry, the retrospective estimation of radiation dose based on observed biological damage; 2) Ongoing analyses of lymphocytes from astronauts. Chromosomal analysis of astronaut lymphocytes provides a measure of accumulated genetic damage caused by space radiation exposure. Chromatid paints will increase sensitivity of this analysis by adding a new class of observable aberrations; and 3) Biology-based space radiation risk analysis efforts. Chromosome aberrations play a causative role in carcinogenesis (as does gene copy number imbalance and cytogenetically invisible point mutations). One way to bring knowledge of cancer genetics into risk analysis is to estimate dose- and LET-dependent probabilities for specific cancer-related genetic alterations. For this approach to work it will be necessary to identify all of the major genetic changes that transform a normal cell into a cancer cell. Adequate investigation of cancer-specific chromosomal inversions is currently not possible, and therefore many such inversions, especially small ones, may remain undiscovered. This shortcoming is particularly pertinent with regard to charged particles in that small inversions are likely to be the most common stable chromosome aberration created by them. Chromatid paints have the potential to contribute to biology-based risk analysis through their ability to reveal these predicted small cancer-related inversions for the first time.

POTENTIAL NON-NASA COMMERCIAL APPLICATIONS (Limit 1500 characters, approximately 150 words)
We expect that chromatid paints will fulfill multiple needs in several fields related to human health. Markets include, but are not limited to: clinical cytogenetics (cancer diagnosis and prognosis, infertility diagnosis, genetic counseling); biomedical research (mechanistic studies of cancer induction, radiation effects, and chemical toxicology); and biodosimetry (retrospective evaluation of radiation exposure as might occur accidentally or from a terrorist attack). Multi-color chromatid paints will provide genome-wide translocation identification, just as mFISH and SKY currently do, and in addition will allow simultaneous and sensitive detection of inversions, making it highly probable that chromatid paints will eventually capture much of the market currently held by chromosome paints.

NASA's technology taxonomy has been developed by the SBIR-STTR program to disseminate awareness of proposed and awarded R/R&D in the agency. It is a listing of over 100 technologies, sorted into broad categories, of interest to NASA.

Biomedical and Life Support
Biomolecular Sensors

Form Generated on 11-24-08 11:56