(Fast-Track proposals will be accepted.)
Number of anticipated awards: 4–6
Budget (total costs):
Phase I: $300,000 for 9 months;
Phase II: $1,000,000 for 2 years
It is strongly suggested that proposals adhere to the above budget amounts and project periods. Proposals with budgets exceeding the above amounts and project periods may not be funded.
The deadline for receipt of all contract proposals submitted in response to this solicitation has expired. It was: November 13, 2012 by 5 p.m. EST.
Glycans play important roles in cell recognition, motility, signaling processes, cell differentiation, cell adhesion, microbial pathogenesis, and immune recognition. Carbohydrate-based high throughput assays (e.g. glycan microarrays, nanoparticles) hold great promise for the rapid analysis of carbohydrate binding proteins (CBPs), elucidation of CBP biology, and the development of diagnostics, vaccines, and therapeutics for a number of diseases, including cancer. However, the utility of these high throughput assays is limited by the paucity of robust biologically relevant glycan libraries available for screening. Glycan standards are also needed to perform structural analysis, especially for monitoring changes in glycosylation that can significantly affect protein function and the safety and efficacy of bio-therapeutics.
NCI participates in trans-NIH initiatives to further glycomics research as part of the Alliance of Glycobiologists for Detection of Cancer, which partners with NCI's Early Detection Research Network, as well as the Glycomics and Glycotechnology Biomedical Technology Research Centers and the Consortium for Functional Glycomics which are funded by NIGMS. Small businesses that develop new glycan libraries for defining the specificities of CBPs, probing the immune response, screening for cancer-associated glycan biomarkers, and enabling glycan structural analysis will more rapidly advance the field of glycomics.
Contract offerors must be cognizant of the current cost and intellectual property rights challenges that have restricted the use of chemical libraries in basic, preclinical, and translational research, and be willing to abide by NIH policies pertaining to the sharing and dissemination of unique research resources developed with NIH funding. Abiding by the NIH Principles and Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining and Disseminating Biomedical Research Resources will ensure that libraries and data generated from them will be deposited into existing repositories and databases that will serve as resources for the entire glycobiology community for non-commercial research purposes.
The goals of this program are to support the synthesis and commercial distribution of robust, well-characterized new carbohydrate libraries that are amenable to being functionalized/linkered for use in high throughput assays, are useful as standards in mass spectrometry (MS) and nuclear magnetic resonance (NMR) applications, and can be used to expand existing screening platforms, structural assays, and additional tool development. These libraries would need to be made with appropriate quality control documentation, and at reasonable cost.
The Expanding the Chemical Space for Carbohydrates: Roadmap to Automated Synthesis workshop report, presented to the NIGMS National Advisory Council in 2011, highlights the critical need for comprehensive chemically-defined glycan libraries for: development of screening platforms with sufficient numbers of structures and diversity to cover the major sectors of mammalian glycomes, use as analytical standards, use as substrates for enzymology, and use as building blocks to increase the glycan chemical space with newly identified enzymes. For analytical standards, biologically relevant groups of related structures with emphasis on isomers will be most useful. Compound collections that provide a basis for development of MS or NMR-based experimental conditions for differentiation of closely related structures are highly desirable. Based on current literature, a 10k-12k glycan collection is needed to represent the functional human glycome, and populate a comprehensive glycan array in a manner that would significantly move the field of glycomics forward. Presently, estimates suggest that only 1000 or so glycans have been synthesized for research purposes, and of these, only a few hundred are commercially available.
A number of NIH institutes (NIGMS, NCI, NIAID, NHLBI) support specific efforts in glycomics and several others (NIDDK, NIDCR, NICHD, NIAMS) also have interests in glycobiology. Discovery labs in The Alliance of Glycobiologists for Detection of Cancer, supported by NCI have a current need for libraries of glycans to facilitate structural studies and high-throughput analysis of carbohydrates derived from biological sources. SBIR contracts focused on synthesis of chemically defined glycan libraries that represent important subsets of the human glycome including representative N- and O- linked glycan libraries, glycan structures found on glycosphingolipids, and libraries of glycosaminoglycan oligomers, would speed progress towards a comprehensive mammalian glycan library. Ready access to these reagents is expected to speed progress in the emerging field of glycomics. Compounds must be synthesized and purified utilizing best practices to >98% purity as established by NMR.
It is recommended that offerors focus their proposals on developing at least one robust glycan library of significant complexity. Libraries of free, reducing-end glycans required include, but are not limited to:
Hybrid-type and complex N-glycan core structures with various multiples of antennae
Human Blood Group Antigens
Glycosphingolipid head groups
Phosphorylated mannose glycans