The mammalian olfactory system is composed of 1000 different receptors on over 1000 cells each, and although individual receptors may be only modestly sensitive and selective, in the aggregate they are capable of fine differentiation of trace odorants through parallel molecular recognition events The interplay between multiple copies of the same receptor and parallel processing of cross-reacting receptors is an area of current interest. Artificial sensors susceptible to facile variations of the binding site would permit investigation of parallel recognition as a strategy for analyte identification. Our recent discovery of oligonucleotides with a hydrophobic variable domain within the fixed frameworks of three- and four-way junctions allows construction of the several thousand distinct molecular sensors needed for such an investigation. Therefore, an array of cross-reacting hydrophobic sensors based on DNA will be constructed to model the olfactory system. The array will provide an instantaneous fingerprint of all molecules with hydrophobic domains present in a solution A typical array at the end of funding period will consist of one to several hundred selected molecular sensors organized in 1586-well plates with multiple readings per sensor. The arrays will be validated on urine specimens collected for metabolite screening. The hydrophobic fingerprints will be correlated with disease states. This approach will be initially demonstrated on Cushing's disease, adrenal adenoma, adrenal carcinoma, hirsutism and congenital adrenal hyperplasia. In the next phase, DNA-based cross-reactive sensors for oligosaccharides will be incorporated into arrays to expand the panel of metabolites that could be profiled in a single-step assay. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB000675-03
Application #
6783291
Study Section
Special Emphasis Panel (ZRG1-SSS-F (02))
Program Officer
Korte, Brenda
Project Start
2002-09-30
Project End
2006-02-28
Budget Start
2004-09-01
Budget End
2006-02-28
Support Year
3
Fiscal Year
2004
Total Cost
$367,875
Indirect Cost
Name
Columbia University (N.Y.)
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
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Kolpashchikov, Dmitry M; Stojanovic, Milan N (2005) Boolean control of aptamer binding states. J Am Chem Soc 127:11348-51
Kolpashchikov, Dmitry M (2005) Binary malachite green aptamer for fluorescent detection of nucleic acids. J Am Chem Soc 127:12442-3
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Stojanovic, Milan N; Stefanovic, Darko (2003) A deoxyribozyme-based molecular automaton. Nat Biotechnol 21:1069-74