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289 Physical Property-Based High-Throughput Protein Sequencing

Number of anticipated awards: 2

(Fast-Track proposals will be accepted.)

Budget (total costs): Phase I: $150,000;
Phase II: $750,000

(Note: It is strongly suggested that Proposals adhere to the above budget amounts. Proposals with budgets exceeding the above amounts may not be funded. Phase I project periods may last a maximum of 9 months.)

The deadline for receipt of all contract proposals submitted in response to this solicitation is: November 9, 2009.

Summary:
The availability, in recent years, of the nucleotide sequences of entire genomes, has radically reshaped approaches to protein sequencing. Protein sequencing by tandem mass spectrometry (LC/MS/MS & MALDI-TOF/MS) involves taking a protein and digesting it into peptides, with subsequent spectra obtained for the major peptide ions. The sample spectra are then matched to theoretical spectral sequences of proteins derived from the human genome (or genome of an organism). While this method has become popular over the recent years due it's relatively high-throughput, the process heavily relies on algorithms that tend to produce false protein identifications. Furthermore, proteomics experiments identify proteins on the basis of several sequenced peptides, which might or might not distinguish between all the possible isoforms of the protein. As a result, the theoretical sequence approaches that are used to identify proteins are not optimal for proteomics experiments. Some estimates indicate that up to 90% of tandem mass spectra in a typical liquid chromatography tandem mass spectrometry analysis cannot be identified using database search algorithms due to the poor quality of the spectra.

Therefore, the NCI is interested in proposals that focus on the development of novel, fast, reliable and economical protein sequencing alternative technologies that rely on approaches other than tandem mass spectrometry involving theoretical spectral sequences. The purpose is to stimulate the community to develop new HT-protein sequencing technologies based solely on physical, chemical, or biological properties. Proposals should explicitly describe how the proposed technology/system will rely on sequencing solely-based on physical, chemical, or biological properties where the full protein is sequenced in a manner equivalent of N-terminal Edman sequencing and amino acid analysis, and does not use theoretical sequencing methods or algorithm involvement, as is the case with mass spectrometry-based sequencing methods.

Project Goals:
The purpose of this project is to stimulate the development of novel, fast, reliable and economical alternative protein sequencing & identification technologies that rely solely on physical properties, equivalent of N-terminal Edman sequencing. Thus, classical tandem mass spectrometry coupled to theoretical spectra or mass spectrometry coupled to spectral libraries will not be explored. Furthermore, the spirit of this proposal is not to support the development of autosamplers that increases the number of samples to a classic Edman cyler protein sequencer.

During the phases I and II, offerors are encouraged (but not required) to coordinate and pursue selected antigen targets in the following reference: Malu Polanski and N. Leigh Anderson. (2006) "A List of Candidate Cancer Biomarkers for Targeted Proteomics." Biomarker Insights 2:1-48.