New technology for proteomics and glycomics (SBIR/STTR).

Notice: this program announcement (PA) must be read in conjunction with the current Omnibus Solicitation of the National Institutes of Health (NIH), Centers for Disease Control and Prevention (CDC), and Food and Drug Administration (FDA) for Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) Grant Applications. The solicitation (see http://grants. nih.gov/grantslfunding/sbirsttr1/index.pdf or http://grants.nih.gov/grants/funding/sbirsttr1/index. doc) contains information about the SBIR and STTR programs, regulations governing the programs, and instructional information for submission. All of the instructions within the current SBIR/STTR Omnibus Solicitation apply.

The principal limitations in the field of proteomics are technological in nature. Proteomics, and the sub-discipline of glycomics, are rapidly developing, technology-intensive fields. Separations, mass spectrometry, microarray, bioinformatics, and other tools have advanced rapidly to support the explosive growth of biomedical applications in this area. However, technologies and methods remain largely inadequate to address the majority of meaningful biological problems, particularly with respect to quantitative and real time measurements. Continued intensive development of advanced tools is essential to meet two needs. First, improvements in basic bioanalytical technologies are essential to these endeavors. This includes but is not restricted to robotics, sample preparation and pre-fractionation, analytical separations, gel and array imaging, quantitation, mass spectrometry, intelligent automated data acquisition, and database searching. Second, improved informatics technologies are essential for the conversion of data into meaningful results and interaction models. Improved informatics tools will also facilitate the integration and synergistic development of the basic analytical tools mentioned above. Additionally, the translation of advances in proteomics to a clinical setting should be a priority.

Proteomics is a rapidly expanding field. Many of the potential scientific and medical rewards of proteomics' successful application to complex systems seem deceptively near. A broad range of technologies is evolving rapidly to meet the needs of the field. However, despite explosive growth in both academic and commercial efforts, concrete technical capabilities are far from adequate to realize this promise. Proteomics technologies and methods in the three broad, interacting domains of biology, analytical chemistry, and informatics are still largely inadequate to address the bulk of challenging biological problems. This is the case with respect to both core capabilities and scale.

The broad scope of proteomics might perhaps be broken down into six types of questions that are addressed in some form: (1) identification of individual proteins, (2) recognition of protein interactions, (3) relative quantitation to distinguish differential expression of proteins, (4) characterization of post-translational modifications, (5) qualitative or quantitative measurements at high spatial and/or temporal resolution to address the dynamics of protein interactions, and (6) formulation of models based on results from components 1-5.

The categories above define the type of information being sought, and imply the need for technologies capable of addressing the challenges inherent in each type of experiment. Those specific technologies may reside within any of the three domains that define proteomics, or may function as a bridge between them. For example, tools for tissue or subcellular fractionation may reside squarely in the biological domain, but could also be designed in such a way as to maximize synergy with widely used analytical separations methods.

It is important that in a field as complex and interdisciplinary as proteomics, technology development be pursued with a sound understanding of context. One area of particular interest is the development of technologies that will permit observations to be quantitative and made in real time, whether for clinical studies or experimental systems.

In addition to the development of broadly applicable research tools that address the core technical challenges in proteomics, unique constraints in two subordinate areas merit special attention. We especially encourage applications in response to this announcement that address the unique needs of glycomics and clinical proteomics, described below.

The application of proteomics tools in the clinical setting lags far behind their use in basic science and drug discovery. Though this is not due solely to technological constraints, the unique challenges associated with development of simple, rapid, and robust technologies for the clinic demand a somewhat different perspective than might be taken in consideration of a purely research-driven project. Likewise, this difference in perspective and priorities should open the possibility, of approaches that might be wholly inadequate from a research perspective but may be appropriate in the clinic. Finally, the exploitation of insights previously developed in research-oriented proteomics to develop more specific, robust tools for clinical applications is also an appropriate goal.

The complexity and diversity of glycosylation significantly complicates the linkage between genetic sequence and mature, active proteins. Glycobiology-focused proteomics, or glycomics, requires the development of novel approaches and tools directed at the special challenges of glycobiology. Among post-translational modifications, glycosylation is the only one that requires structural characterization of the modifying moiety beyond noting its presence. Strategies for separation, profiling, quantitation, and detailed characterization of carbohydrate structures are central challenges. Informatics tools are needed for data handling and reduction, correlation of carbohydrate and protein information, and a variety of other purposes. Discovery-based analytical tools that can survey the complexities of glycosylation on a system-wide basis may have significant biological impact.

The goals of this PA are deliberately discussed with respect to fundamental challenges, rather than in relation to specific technologies, in order to emphasize the overriding importance of surmounting obstacles, irrespective of the analytical strategy adopted to pursue those solutions. This solicitation is open to unconventional or alternative approaches.

This PA uses the SBIR and STTR mechanisms, which are set-aside programs. As an applicant, you will be solely responsible for planning, directing, and executing the proposed project. Future unsolicited, competing- continuation applications based on this project will compete with all SBIR/STTR applications and will be reviewed according to the customary peer review procedures.

This PA uses just-in-time concepts. It also uses the modular budgeting format. Specifically, if you are submitting an application budget of $100,000 total costs (direct, F&A and fee) or less, use the modular format and instructions as described in the current SBIR/STTR Omnibus Solicitation. Otherwise follow the instructions for non-modular budget research grant applications. This program does not require cost sharing as defined in the current NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/ nihgps_2003/NIHGPS Part2.htm#matching_or_cost_sharing.

Applications may be submitted for support as Phase I STTR (R41) or Phase I SBIR (R43) grants; Phase II STTR (R42) or Phase II SBIR (R44) grants; or the SBIR/STTR FAST-TRACK option as described in the SBIR/STTR Omnibus Solicitation. Phase II applications in response to this PA will only be accepted as competing continuations of previously funded NIH Phase 1 SBIR/STTR awards. The Phase II application must be a logical extension of the Phase I research but not necessarily a Phase I project supported in response to this PA.

The PHS 398 research grant application must be used for all SBIR/STTR Phase I, Phase II and Fast-Track applications (new and revised.) Effective October 1, 2003, applications must have a DUN and Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the Universal Identifier when applying for federal grants or cooperative agreements. The DUNS number can be obtained by calling 866-705-5711 or through the website at http://www.dunandbradstreet. com/. The DUNS number should be entered on line 11 of the face page of the PHS 398 form. The PHS 398 is available at http://grants.nih.gov/grants/funding/phs398/phs398.html. Prepare your application in accordance with the SBIR/STTR Omnibus Solicitation and the PHS 398. Helpful information for advice and preparation of the application can be obtained at: http:/Igrants.nih.gov/grants/funding/sbirgrantsmanship.pdf. The NIH will return applications that are not submitted on the 5/2001 version of the PHS 398. For further assistance contact GrantsInfo, 301-435-0714, e-mail: [e-mail]. The title and number of this PA must be typed on line 2 of the face page of the application.

The CSR will not accept any application in response to this PA that is essentially the same as one currently pending initial review unless the applicant withdraws the pending application. The CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of a substantial revision of an unfunded version of an application already reviewed, but such application must include an introduction addressing the previous critique.

Receipt and review schedule: see http://grants. nih.gov/grants/funding/sbirsttr_receipt_dates.htm.

Contact: Douglas M. Sheeley, Division of Biomedical Technology, National Center for Research Resources, 6701 Democracy Bird, MSC 4874, Bethesda, MD 20892-4874 USA, 301-435-0755, fax: [phone], e-mail: [e-mail]; Pamela A. Marino, NIGMS, Rm 2As.43k, Natcher Building, Bethesda, MD 20892-6200 USA, 301-594-3827, fax: [phone], e-mail: [e-mail]; Susan E. Old, Division of Heart and Vascular Disease, NHLBI, 6701 Rockledge Dr, MSC 7940, Bethesda, MD 20892-7940 USA, 301-435-1802, fax: [phone], e-mail: [e-mail]; Danilo A. Tagle, Neuroscience Center, NINDS, Rm 2133, 6001 Executive Bird, Bethesda, MD 20892-0001 USA, 301-496-5745, fax: [phone], e-mail: [e-mail].

Reference: PA No. PA-04-089