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253 Advances in Protein Expression of Post-Translationally Modified Cancer Related Proteins
Number of anticipated awards: 4
(Fast-Track proposals will be accepted.)
Budget (total costs): Phase I: $150,000;
Phase II: $1,000,000
The deadline for receipt of all contract proposals submitted in response to this solicitation is: 5:00 p.m. Eastern Standard Time Monday, November 5, 2007
Release of a completed polypeptide chain from a ribosome is often not the last chemical step in the formation of a protein. Various covalent modifications often occur, either during or after assembly of the polypeptide chain. Most proteins undergo co- and/or post-translational modifications. Knowledge of these modifications is extremely important because they may alter physical and chemical properties, folding, conformation distribution, stability, activity, and consequently, function of the proteins. Moreover, the modification itself can act as an added functional group. Examples of the biological effects of protein modifications include phosphorylation for signal transduction, ubiquitination for proteolysis, attachment of fatty acids for membrane anchoring and association, glycosylation for protein half-life, targeting, cell:cell and cell:matrix interactions. Consequently, the analysis of proteins and their post-translational modifications (PTMs) is particularly important for the study of heart disease, cancer, neurodegenerative diseases and diabetes.
Therefore, the NCI is interested in proposals that focus on the development of post-translationally modified human proteins (e.g., glycosylation, phosphorylation, acetylation, oxidation). Proposals should explicitly describe how the proposed technology/system will develop/express, isolate and characterize the PTMs.
Project goals:
Increasing demand for recombinant PTM proteins has focused research on techniques for improving protein expression and controlling post-translational processing. The purpose of this project is to stimulate the development on all aspects of PTM protein expression including chemical synthesis, novel cell systems, expression vectors, and culture conditions. Proteins selected for production are to entail low abundance cancer related proteins from bodily fluids in support of the Clinical Proteomic Technologies Initiative (http://proteomics.cancer.gov). These proteins are to become part of CPTI’s Reagents and Resource core.
Phase I activities and expected deliverables:
- Demonstration of feasibility of the innovative PTM development approach.
- Generate at least 10 PTM targets. Offerors must select from the following list of the NCI required targets listed at: http://sbir.cancer.gov/.
- Produce an initial PTM production prototype in working with the Clinical Proteomic Technologies Initiative community.
- Produce evidence that the PTMs are well characterized (preferably using MS-based techniques).
- Demonstrate that PTMs can be made reproducibly and economically.
- Research should be proposed with quantitative feasibility milestones.
Phase II activities and expected deliverables:
- Generate at least 100 PTM targets (targets to be selected in coordination with the Clinical Proteomic Technologies Initiative community).
- PTMs are to be well characterized (preferably using MS-based techniques).
- Project to be done in coordination with the Clinical Proteomic Technology Initiative community to integrate PTMs into the technology assessment programs and greater scientific community.
- Research should be proposed with quantitative feasibility milestones.
Post-Translationally Modified Cancer-Related Proteins of Interest to NCI
The following post-translationally modified cancer-related proteins have been identified as high priority for the NCI. Offerors should propose to generate at least 10 post-translational modification (PTM) targets from the following list:
Post-Translationally Modified Cancer-Related Proteins of Interest to NCI
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