SOLICITATION NOTICE
B -- Deep Interactome Profiling of the Tmem 16A Cl Channel Protein by Co-interacting Protein Identification Technology
- Notice Date
- 2/4/2016
- Notice Type
- Presolicitation
- NAICS
- 541711
— Research and Development in Biotechnology
- Contracting Office
- Department of Health and Human Services, National Institutes of Health, National Heart, Lung and Blood Institute, Rockledge Dr. Bethesda, MD, Office of Acquisitions, 6701 Rockledge Dr RKL2/6100 MSC 7902, Bethesda, Maryland, 20892-7902
- ZIP Code
- 20892-7902
- Solicitation Number
- HHS-NIH-NHLBI-CSB-DE-2016-079-RF
- Archive Date
- 3/1/2016
- Point of Contact
- Rashida S. Ferebee, Phone: 3014352605
- E-Mail Address
-
ferebeers@nhlbi.nih.gov
(ferebeers@nhlbi.nih.gov)
- Small Business Set-Aside
- N/A
- Description
- INTRODUCTION THIS IS A PRE-SOLICITATION NON-COMPETITIVE (NOTICE OF INTENT) SYNOPSIS TO AWARD A PURCHASE ORDER WITHOUT PROVIDING FOR FULL AND OPEN COMPETITION (INCLUDING BRAND-NAME). The National Heart, Lung, and Blood Institute (NHLBI), Office of Acquisitions (OA) on behalf of The National Institute of Dental and Craniofacial Reseach (NIDCR) intends to negotiate and award a Purchase Order without providing for full and open competition (Including brand-name) to Scripps Research Institute for deep interactome profiling of the Tmem16A Cl channel protein by Co-interacting Protein Identification Technology (CoPIT). NORTH AMERICAN INDUSTRY CLASSIFICATION SYSTEM (NAICS) CODE The intended procurement is classified under NAICS code 541711, Research and Development in Biotechnology, with aSize Standard of 500 employees. REGULATORY AUTHORITY The resultant Purchase Order will include all applicable provisions and clauses in effect through the Federal Acquisition Circular (FAC) 05-86 effective 01 FEB 2016. This acquisition is conducted under the procedures as prescribed in FAR subpart 13—Simplified Acquisition Procedures at an amount not exceeding the simplified acquisition threshold ($150,000). STATUTORY AUTHORITY This acquisition is conducted under the authority of the Federal Acquisition Regulation (FAR) Part 13—Simplified Acquisition Procedures, Subpart 13.106-1 (b) (1), Soliciting from a single source and is not expected to exceed the simplified acquisition threshold. Contracts awarded using FAR Part 13—Simplified Acquisition Procedures are exempt from the requirements of FAR Part 6—Competition Requirements. FAR Subpart 6.302-1—Only one responsible source and no other supplies or services will satisfy agency requirements 41 U.S.C. 253(c)(1), provides the authority to sole source. DESCRIPTION OF REQUIREMENT Background The National Institutes of Health (NIH) is the nation’s leading medical research agency and the primary Federal agency conducting and supporting medical discoveries that improve people’s health and save lives. The mission of the National Institute of Dental and Craniofacial Research (NIDCR) is to improve oral, dental and craniofacial health through research, research training, and the dissemination of health information. The Melvin Laboratory, Secretory Mechanisms and Dysfunction Section (SMDS), NIDCR/NIH, and the Yates Laboratory at The Scripps Research Institute (SRI) have a long-standing scientific collaboration over the past decade. The physiology expertise of the Melvin Laboratory and the development of cutting-edge proteomic methods by the Yates Laboratory have been combined to characterize novel aspects of salivary gland function. This collaboration has resulted in nine joint publications to date. It is estimated that one out of every four or five persons will suffer from xerostomia (dry mouth) during their lifetime. The clinical costs of dry mouth include mucosal infections and ulcers, altered taste, dysphagia and pain. To develop specific and effective interventions to treat dry mouth it is necessary to understand the molecular nature of the fluid secretion process. Acinar cell fluid secretion is driven by transcellular Cl movement. The Melvin Laboratory has recently shown that activation of an apical Ca2+-dependent Cl channel encoded by the Tmem16A gene (Catalán et al., 2015) is the obligatory, rate-limiting step in fluid production. Although it is clear that Ca2+ directly activates Tmem16A, it is unknown how sustained activity of the Tmem16A channel is maintained/regulated. Purpose and Objectives The SMDS, in collaboration with the contractor, will develop antibody-based protein enrichment methods to isolate the plasma membrane-associated Tmem16A channel proteins from acutely isolated native mouse acinar cells. Period of Performance Base Year: February 17 th, 2015 – February 16 th, 2017 Option Period 1: February 17 th, 2017 – August 17 th, 2017 Performance Location National Institutes of Health, NIDCR 10 Center Drive Building 10 Bethesda, MD 20892 Project Description Contractor Tasks/Deliverables: 1) The below tasks are to be executed sequentially. a. The contractor and the NIDCR shall develop a customized experimental procedure that addresses several issues associated with enrichment of membrane protein interactomes: (a) highly efficient recovery of membrane proteins from cell lysates while preserving interactions, (b) insolubility and aggregation of membrane proteins during IP and subsequent elution, (c) removal of lipids and other contaminants that may cause signal suppression during electrospray ionization, and (d) compatibility with in-solution digestion, chromatographic separation and mass spectrometric detection; b. The contractor shall use MUDPiT (multidimensional protein identification technology) to determine the molecular identifies of the isolated proteins and simultaneously acquires the PTM (post-translation modification) state of these proteins; c. The contractor shall use CoPIT (Co-interacting Protein Identification Technology) to determine the specificity of protein interactions in comparison to control experiments for label-free data by using novel methods for unbiased subtraction of background interactions; d. The contractor and the NIDCR shall use the interactomes from individual experimental conditions to compare against each other to yield differential interactomes based on spectral counting. The Radial Topology Viewer, a visualization tool, graphs interactors, whereby the arithmetic distance to the bait in the center can reflect a dynamic variable of the user’s choice, for example confidence of interaction or change in strength of interaction. Additional relational information on protein-protein interactions gathered from other databases can be included to enable the contextual interpretation of a protein interactome; e. The contractor and the NIDCR shall confirm the significance of protein interactomes and PTMs identified above by co-expression and mutational functional analysis, respectively. 2) Deliverables a. May 14, 2016: Complete the development and use of the customized experimental procedures for efficient recovery of membrane proteins from cell lysates while preserving interactions; b. August 14, 2016: MUDPiT and CoPIT analyses will be performed, i.e. the molecular identifies of the isolated proteins and the specificity of protein interactions will be completed; c. November 14, 2016: Interactomes from individual experimental conditions will be compared against each other to yield differential interactomes based on spectral counting; d. February 14, 2016: The functional significance of protein interactomes will be confirmed by co-expression and mutational analysis; e. Interim progess reports will be provided upon request or following a milestone, whichever comes first. 3) Government Requirements a. The NIDCR will work in conjunction with the contractor to develop a customized experimental procedure, analyze MUDPiT and CoPIT results, and perform experiments to test the significance of protein interactomes and PTMs by co-expression and mutational functional analysis. Other Important Considerations 1) The contractor will use MUDPiT and CoPIT methodologies developed by the Yates Laboratory. The methods are a combination of customized hardware and unique analyses software. CONTRACTING WITHOUT PROVIDING FOR FULL OR OPEN COMPETITION (INCLUDING BRAND-NAME) DETERMINATION Justification Rationale: Only one source is available: The determination by the Government to make a single-sole source is based upon the market research conducted as prescribed in FAR Part 10—showing that Scripps Research Institute (SRI) is the only responsible source. The MUDPiT and CoPIT methodologies were developed by the Yates Laboratory and are a combination of customized hardware and unique analyses software. As the developer of CoPIT, SRI is the only known entity with the capability to perform the methodology. CoPIT is unique because it allows for comprehensive identification and analysis of membrane protein interactomes and their dynamics, it integrates experimental and computational methods to address limitations of current methods for protein interaction analysis. The functional activity of ion channels often relies on highly complex protein networks, which are dynamically regulated in time and space. However, the identification of protein interaction networks remains a major challenge because a comprehensive analysis requires high co-purification yields of the “bait” protein and its interactors to differentiate true interactors from non-specific background. Ion channel interactomes are particularly difficult to explore because of the generally lower abundance, hydrophobic nature, and partial protection of protease cleavage sites by lipid layers. Because of these technical challenges, the interactome of most ion channel proteins have not been characterized. Nevertheless, it is important to elucidate the interactomes of membrane proteins such as ion channels, transporters and receptors because they represent the most promising druggable target proteins for many diseases. The study of membrane protein interactomes is often performed with baits that are tagged with an epitope to increase protein enrichment efficiency. However, epitope tagging increases the potential for mis-sorting or mis-folding of membrane proteins. CoPIT is an experimental and computational tool that allows the comprehensive characterization of endogenous membrane as well as non-membrane protein interactomes using immunoprecipitations. Dr. Yates’ group has developed an optimized experimental protocol that provides enhanced sensitivity and efficiency and novel data analysis algorithms that allows an unbiased discrimination of highly confident from less confident interactors as well as to determine interactome changes between experimental conditions. Interacting proteins can be graphed in a specialized network visualization tool (Radial Topology Viewer) that maps statistical significance of the interactions. CoPIT enables a complete workflow from sample preparation to network analysis tailored to dissect the interaction dynamics of a single bait protein with all of its binding partners. CLOSING STATEMENT This synopsis is not a request for competitive proposals. However, interested parties may identify their interest and capability to respond to this notice. Responses to this notice shall contain sufficient information to establish the interested parties’ bona-fide capabilities for fulfilling the requirement and include: unit price, list price, shipping and handling costs, the delivery period after contract award, the prompt payment discount terms, the F.O.B. Point (Destination or Origin), the Dun & Bradstreet Number (DUNS), the Taxpayer Identification Number (TIN), and the certification of business size. All offerors must have an active registration in the System for Award Management (SAM) www.sam.gov.” A determination by the Government not to compete this proposed contract based upon responses to this notice is solely within the discretion of the Government. The information received will normally be considered solely for the purposes of determining whether to proceed on a non-competitive basis or to conduct a competitive procurement. All responses must be received by February 15 th, 2016 9:00 AM EST and must reference number NHLBI-CSB-DE-2016-079-RF. Responses may be submitted electronically to Rashida Ferebee, ferebeers@nhlbi.nih.gov. Fax responses will not be accepted. “All responsible sources may submit a capability statement, proposal, or quotation, which shall be considered by the agency.”
- Web Link
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FBO.gov Permalink
(https://www.fbo.gov/spg/HHS/NIH/NHLBI/HHS-NIH-NHLBI-CSB-DE-2016-079-RF/listing.html)
- Place of Performance
- Address: Scripps Research Institute, La Jolla, California, 92037, United States
- Zip Code: 92037
- Zip Code: 92037
- Record
- SN04011291-W 20160206/160205000024-2fed4fe487a787b1b98ed3c712473162 (fbodaily.com)
- Source
-
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