| Request for Proposal No.: | NHLBI-DR-99-18 |
| Issue Date: | February 5, 1999 |
| Issued By: | Patricia A. Smith Contracting Officer NIH/NHLBI Contracts Operations Branch II Rockledge Centre 6701 Rockledge Drive, MSC 7902 Bethesda, Maryland 20892-7902 |
| Purchase Authority: | Public Law 95-83, as amended |
| Small Business Set-Aside: | No, SIC Code 8733 |
| Proposal Intent Due Date: | February 19, 1999 |
| Proposal Due Date: | March 8, 1999, 4:30 P.M. (Eastern Time) |
Ladies and Gentlemen:
The National Heart, Lung, and Blood Institute (NHLBI) is soliciting proposals on behalf of the National Institute of Dental and Craniofacial Research (NIDCR) for services to characterize novel human genes expressed preferentially in embryonic rhombomeres and first branchial arch, oral cavity (including teeth, salivary glands and tongue), and maxilla. This Streamlined Technical Request For Proposal (RFP) consists of this combined solicitation form and cover letter (PART A), and three additional components, as follows:
These components contain the technical information required for the submission of a proposal for this acquisition. In addition, there are two other sections in this specific RFP. The section entitled "Specific RFP Instructions and Provisions" contains, for example, the proposal intent response form and the address for delivery of your proposal. The section entitled "Applicable RFP References" lists those items in the STREAMLINED RFP REFERENCES directory that apply to this RFP, including forms for submission of the proposal.
Although these documents contain sufficient information for you or your organization to submit a proposal, if you intend to submit a proposal in response to this RFP, IT IS ESSENTIAL THAT YOU IMMEDIATELY NOTIFY PATRICIA A. SMITH, CONTRACTING OFFICER, AT THE FOLLOWING INTERNET ADDRESS:
IF YOU DO NOT NOTIFY THE CONTRACTING OFFICE OF YOUR INTENT TO SUBMIT A PROPOSAL, YOU WILL NOT RECEIVE AN INDIVIDUAL NOTICE OF ANY AMENDMENTS TO THE RFP, IF ANY ARE ISSUED. HOWEVER, ALL AMENDMENTS WILL BE POSTED ON THE NIH WEB SITE.
The original and twenty-five (25) copies of your technical proposal and the original and six (6) copies of your business proposal must be received by the Contracting Office no later than March 8, 1999, at 4:30 p.m. local time at the address listed in the item entitled "Packaging and Delivery of Proposals". Also, please complete the form entitled "Proposal Intent Response Sheet" and send it to the address indicated therein on or before February 19, 1999. This will allow us to expedite preparations for the peer review of proposals. Finally, your proposal must be organized and submitted in accordance with the "Technical Proposal Table of Contents." All three of these items are found under the "Specific RFP Instructions and Provisions" portion of this RFP, which follows the technical evaluation criteria section.
You are reminded that the "Technical Proposal Cover Sheet" must be completed in full detail and used as the cover sheet for each copy of your technical proposal. (This form is contained in this NIH WEB site under the FORMS, FORMATS, AND ATTACHMENTS file found in STREAMLINED RFP REFERENCES.) This information will be used to ensure that there will be no conflict of interest when selecting review committee members.
Offers will be valid for 120 days unless a different period is specified by the offeror on the form entitled, "Proposal Summary and Data Record, NIH 2043" also located at the site for FORMS, FORMATS, AND ATTACHMENTS.
NOTE: IF YOUR PROPOSAL IS NOT RECEIVED BY THE CONTRACTING OFFICER OR DESIGNEE AT THE PLACE AND TIME SPECIFIED, THEN IT WILL BE CONSIDERED LATE AND HANDLED IN ACCORDANCE WITH THE PHS CLAUSE 352.215-10 ENTITLED, "LATE PROPOSALS, MODIFICATIONS OF PROPOSALS, AND WITHDRAWALS OF PROPOSALS". The full text is in the Optional RFP Instructions and Provisions file of the Streamlined RFP References Directory.
If you have any additional questions regarding this RFP, please contact Mrs. Smith through the Internet using the electronic mail address listed above or phone (301) 435-0345, fax (301) 480-3430. COLLECT CALLS WILL NOT BE ACCEPTED.
SUBMISSION OF PROPOSALS USING FACSIMILE OR ELECTRONIC MAIL IS NOT AUTHORIZED.
NOTE: DIRECTIONS FOR ACCESSING THE "STREAMLINED RFP REFERENCES" REFERRED TO THROUGHOUT THIS RFP ARE AS FOLLOWS:
After reviewing this Request For Proposal, click here to return to the original site for the NIH Request For Proposals Directory. In this directory, entitled "NIH Request For Proposals Directory", following the list of NIH Institutes by name, is the section entitled "STREAMLINED RFP REFERENCES". Select (click on) each section you wish to review:
"STANDARD RFP INSTRUCTIONS AND PROVISIONS" for proposal preparation instructions and other standard provisions,
"OPTIONAL RFP INSTRUCTIONS AND PROVISIONS" for the special provisions identified in this specific RFP,
"FORM, FORMATS, AND ATTACHMENTS" to download the forms listed in this specific RFP that you will need to submit a proposal,
"REPRESENTATIONS AND CERTIFICATIONS" to download and complete the representations and certifications that must be submitted with your proposal, and
"SAMPLE CONTRACT FORMAT-GENERAL" to view some of the clauses that are typical for inclusion in a Research and Development type contract issued by NIH.
Recent advances in DNA sequencing technology now enable researchers to discover previously unknown genes by automated sequencing of randomly selected clones from complementary DNA (cDNA) libraries prepared from specific tissues (1-4). Genes expressed specifically in a particular tissue can be enriched by subtraction of cDNA sequences expressed in other tissues (5-11), or they can be identified by comparative screening methods that include SAGE (serial analysis of gene expression), cDNA microarray chip screening (12-15), and other approaches.
A unique opportunity exists for the National Institute of Dental and Craniofacial Research to accelerate current research on the genetics and biology of human craniofacial development and disorders (e.g. see refs. 16-20) by generating and applying these powerful new tools in an NIDCR genome project to discover novel human craniofacial genes. Several current needs addressed by such a project will include: a) the need for new DNA reagents by molecular and developmental biologists to determine which genes are essential in human craniofacial development; b) the need for sets of candidate genes for much more rapid gene mapping in linkage studies of human craniofacial defects; such genes can be identified by projects to discover novel genes that are active in craniofacial development; and c) a general need for a validated, centralized source of human craniofacial genes, sequence data, and probes.
Potential fruitful approaches to reach these goals have been explored by Intramural researchers in the Craniofacial Developmental Biology and Regeneration Branch, who have successfully demonstrated the practicality of a broad search for previously unknown tooth and craniofacial genes in initial studies using rodent systems (21-24). The approaches involved generating tissue-specific cDNA libraries, random DNA sequencing, characterization of novel craniofacial genes, antibody production against selected clones to characterize protein expression and to probe function, candidate gene mapping, and linkage to a human genetic defect. This proposed contract will extend these approaches to human craniofacial genes, combined with the establishment of a national resource that would provide direct access to a sequence database, human craniofacial cDNA clones, and both published and unpublished data for free use by members of the craniofacial-oral-dental research community.
The purpose of this contract is to discover and to begin to characterize novel human genes expressed preferentially in embryonic rhombomeres and first branchial arch, oral cavity (including teeth, salivary glands and tongue), and maxilla. It will provide a national resource of novel data and human DNA clones relevant to oral and craniofacial genetics and development.
The characterization of genes involved in human craniofacial embryonic development should accelerate research into a variety of human syndromes and disorders affecting the craniofacial complex. Examples include inherited and acquired congenital disorders involving defects in critical genes and/or in genes-environmental interactions, tissue repair processes that use mechanisms which often overlap embryonic remodeling mechanisms, and inherited and acquired oral cancers expressing embryonic markers (e.g., Gorlin syndrome).
Congenital defects involving the craniofacial complex afflict 5% of all infants born in the United States. The human and economic costs are enormous--the lifetime costs for just one year's cohort of children born with cleft lip or palate in the U.S. is estimated to be nearly $1 billion. Determining the genetic basis for these inherited and acquired disorders should lead to improved diagnostics and genetic counseling, as well as novel approaches to potential therapy and prevention based on the discovery of new genes and their regulation (16-20). These advances are essential to reduce this formidable medical, social, and economic problem.
Although approaches conceptually similar to those in this contract will eventually be applied to tens of thousands of other novel genes from other tissues identified in the Human Genome Project, craniofacial sites of gene action are unusually visible, and they represent by far the most common sites of congenital defects. Even so, disorders of craniofacial tissues are not primary therapeutic targets of pharmaceutical and biotechnology companies, and it is unlikely that any company would generate the proposed libraries or data. Nevertheless, identifying and characterizing individual craniofacial genes important in development should provide valuable insights into pathophysiology, as well as providing targets for diagnosis and therapy. Opportunities for potential therapeutic approaches include in utero preventive drug therapy, potential gene therapy in mothers identified as having a genetic predisposition to a particular craniofacial congenital defect, and novel biologically-based therapeutics that include biomimetics, biomaterials, and tissue engineering.
Many craniofacial anomalies and increasing numbers of cancers are caused by a mutation or a defect in the function(s) of one or more genes (17-20). An increasing number of mutations have been identified for craniofacial syndromes, and a number of scientific opportunities have been identified to pursue studies designed to understand the molecular mechanisms required for sequential craniofacial, oral, and dental development at the molecular level. Innovative approaches appear warranted that involve the identification and cataloging of regulatory and structural genes involved in various stages of human craniofacial development as a logical first step to identify the causes of anomalies. The identification of the genes whose expression is highly tissue- and stage-specific during development of the craniofacial complex is important, since these gene products are likely to play key roles in the formation of its tissues.
Discovery of many novel proteins and genes, as well as further antibody and functional characterization, is now possible using molecular cloning, random DNA sequencing of appropriately high-quality "libraries" of gene products, and creative screening approaches for genes expressed in a specific tissue and at particular developmental stages (1-15). In a preceding NIDCR program to identify novel genes expressing in developing mouse and rat tooth and craniofacial tissues, database analyses indicated that roughly 35-50% of randomly sequenced clones have varying degrees of homology to known genes, but that the remaining 50-65% were never described previously and are therefore unique (e.g. see ref 21). Not surprisingly, a number of the previously identified genes in a tooth cDNA library were found to encode extracellular matrix proteins including such genes as amelogenin, collagen, and tenascin, but novel genes such as ameloblastin (22) and Krox 26 (24) have also been identified. This approach should lead to the discovery of many new genes.
Defining key genes and their functions will be useful not only for the identification of susceptible developmental steps and causes of disease, but also potentially in the future for screening and generating animal models to test novel in utero therapeutic approaches (e.g., dietary alterations to bolster defective gene function). This project will benefit the public by providing the potential for new approaches to prevention and possible gene therapy, e.g. dietary and drug strategies for preventing craniofacial anomalies, and it may also eventually provide markers for oral cancers for diagnostic applications, as well as novel biomimetics and other biologicals.
Independently, and not as an agent of the Government, the contractor shall furnish the necessary services, qualified personnel, equipment, facilities, and materials, not otherwise provided by the Government, to characterize novel human genes expressed preferentially in embryonic rhombomeres and first branchial arch, oral cavity (including teeth, salivary glands and tongue), and maxilla.
Specifically, the Contractor shall:
The contractor shall strive to generate maximal numbers of full-length clones in representative libraries. Sources of these libraries shall include embryonic rhombomeres (i.e. 1-8) and first branchial arch, oral cavity (teeth, salivary glands and tongue), and maxilla. These libraries shall include standard, normalized, subtraction, and possibly SAGE libraries. The anticipated number of cDNA (and possibly SAGE) libraries shall be at least one dozen.
Tentative tissues and stages shall be: Stage A: combined rhombomeres (i.e. 1-3, 3-5, 5-8) and forming first branchial arch at the time of the initiation of early neural crest cell migration [e.g. 3-5 weeks of gestation]; Stage B: early mandible, tongue, and maxilla [e.g. 6-7 weeks]; although technically difficult, obtaining libraries from early stages such as A and B shall be given particularly high priority; Stage C: maxilla and developing teeth at the time of palate fusion [e.g. 6-8 weeks]; and Stage D: later mandible, maxilla, teeth, and salivary glands [> 22 to < 3 months]. (Note To Offerors: It is anticipated that tissues dissected for Stages A, B, and C will not be combined within each stage, and that tissues dissected for Stage D will also generally be used for separate libraries.)
Standard and normalized cDNA libraries rich in full-length clones shall be prepared from tissues at these stages, with at least one standard cDNA library prepared for each stage. Subtraction libraries shall also be constructed, e.g. stage A tissues versus stage C or D. The contractor shall provide evidence for the presence of cDNA that includes the 5' coding end of a large mRNA species, e.g. for fibronectin or laminin, as well as the for presence of less-abundant cDNA species, such as for growth factors and their cognate receptors. Quality control and characterization of libraries shall also include determining for each the average size of clones, titers of an amplified library, and partial 5' EST sequences of at least one hundred randomly selected clones from each. In addition, subtraction libraries should include an analysis of subtraction efficiency. Other libraries may include SAGE libraries, especially for early stages, as well as representational libraries (the latter may be more appropriate for the separate later-stage tissues).
Gene expression screening methodologies such as high-density colony hybridization, SAGE, dot-blotting, or cDNA microarray chip approaches shall be used as appropriate to identify genes expressed preferentially in specific craniofacial tissues and in stage-specific patterns (5-13). Clones showing interesting patterns of regulation shall be sequenced. (Note To Offerors: Input is encouraged by the offeror for the most useful comparisons, e.g. an initial comparison of gene expression levels or subtracting between specific developmental stages between tissues such as maxilla versus liver, using approaches expected to be practical for small amounts of tissue, efficient, and cost-effective.)
The specific approaches used shall be chosen by the contractor with concurrence of the Project Officers. The individual clones shall be subjected to EST automated DNA sequencing and database searches for homologies and functional motifs. (Note To Offerors: A rough estimate of expected numbers of EST sequences is 1000, besides the number needed for preliminary characterization of libraries).
Data on expression levels of specific clones shall be presented in tabular and pictorial form (e.g., see the format used by the NCI Cancer Genome Anatomy Project site in reference 25). Materials shall be made available by the donation of pertinent cDNA clones and libraries to the American Type Culture Collection for distribution to all qualified investigators.
(Note To Offerors: Offerors are encouraged to provide intellectual input and to propose any approaches that will result in efficient and optimal identification of novel differentially-expressed craniofacial genes, especially from early developmental stages.)
GENERAL
The technical proposal will receive paramount consideration in the selection of the Contractor for this acquisition. In the event that the technical evaluation reveals that two or more offerors are approximately equal in technical ability, then cost may become a significant factor in determining award. In any event, the Government reserves the right to make an award to the best advantage of the Government, cost and other factors considered.
If a foreign R&D proposal is received, the peer review group will address the need or appropriateness of accomplishing the work overseas.
The evaluation will be based on the demonstrated capabilities of the prospective Contractors in relation to the needs of the project as set forth in the RFP. The merits of each proposal will be evaluated carefully. Each proposal must document the feasibility of successful implementation of the requirements of the RFP. Offerors must submit information sufficient to evaluate their proposals based on the detailed criteria listed below.
MANDATORY QUALIFICATION CRITERIA
Listed below are mandatory qualification criteria. The qualification criteria establishes conditions that must be met at the time of receipt of initial proposals in order for your proposal to be considered any further for award.
TECHNICAL EVALUATION CRITERIA
The evaluation criteria are used by the technical evaluation committee when reviewing the technical proposals. The criteria below are listed in the order of relative importance with weights assigned for evaluation purposes.
Total possible points: 100
THE REMAINDER OF THIS RFP CONSISTS OF THE FOLLOWING SECTIONS:
NOTICE TO OFFERORS: This section contains proposal instructions and information which are specifically related to this acquisition. The information provided below is only a portion of the instructions and notices required for the submission of a proposal. References to additional, more general, information and forms regarding proposal preparation are contained under Section III. Applicable RFP References.
The following specific RFP instructions and provisions apply to this Request For Proposal:
RFP No. NHLBI-DR-99-18
TITLE OF RFP: Novel Human Oral and Craniofacial Genes
FURNISH THE INFORMATION REQUESTED BELOW AND RETURN THIS PAGE BY February 19, 1999. YOUR EXPRESSION OF INTENT IS NOT BINDING BUT WILL ASSIST US IN PLANNING FOR PROPOSAL EVALUATION.
Review Branch
NIH, NHLBI
6701 Rockledge Drive, MSC 7924
Bethesda, MD, 20892-7924
Attention: Dr. James Scheirer
or FAX TO: Dr. James Scheirer at (301) 480-3541
Your proposal shall be organized as specified in the "Standard RFP Instructions and Provisions." Shipment and marking shall be as follows:
EXTERNAL PACKAGE MARKING
In addition to the address cited below, mark each package as follows:
"RFP NO. NHLBI-DR-99-18
TO BE OPENED BY AUTHORIZED GOVERNMENT PERSONNEL ONLY"
The number of copies required of each part of your proposal are:
TECHNICAL PROPOSAL: ORIGINAL* AND Twenty-five (25) COPIES
BUSINESS PROPOSAL: ORIGINAL* AND Six (6) COPIES
DELIVER PROPOSAL TO:
If hand delivered or delivery service:
Review Branch
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
Rockledge Building, Room 7091
6701 Rockledge Drive MSC 7924
Bethesda, MD 20817-7924
If using U.S. Postal Service:
Review Branch, Division of Extramural Affairs
National Institutes of Health
National Heart, Lung, and Blood Institute
6701 Rockledge Drive MSC 7924
Bethesda, MD 20892-7924
*THE ORIGINAL PROPOSAL MUST BE READILY ACCESSIBLE FOR DATE STAMPING.
NOTE: The following information is to be used by the offeror in preparing its Representations and Certifications, specifically in completing the provisions entitled, SMALL BUSINESS PROGRAM REPRESENTATIONS, FAR 52.219-1:
The standard industrial classification (SIC) code for this acquisition is 8733.
The small business size standard is $5,000,000 average annual receipts over the three preceding fiscal years.
THIS REQUIREMENT IS NOT SET-ASIDE FOR SMALL BUSINESS. However, the FAR requires in every solicitation (except for foreign acquisitions) the inclusion of the SIC code and corresponding size standard which best describes the nature of the requirement in the solicitation.
It is anticipated that one award will be made from this solicitation and that award will be made in September 1999.
It is anticipated that the award from this solicitation will be a multiple-year cost reimbursement, completion type contract with a period of performance of thirty-nine months, and that incremental funding will be used.
To assist you in the preparation of your proposal, the Government considers the effort to perform this work to be approximately 3 FTE (full time equivalency) each year over the three year performance period. This estimate is furnished for the offeror's information only and is not to be considered restrictive for proposal purposes.
| Labor Category | Level of Effort Each Year |
|---|---|
| Study coordinator/Principal Investigator | 10% |
| research associate | 100% |
| senior technician | 100% |
| technician | 100% |
| Medical/surgical collaborator | 5% |
| Total | 3.15 FTE |
All staffing levels proposed should be accompanied by specific justifications as to the type and hours of work expected to be performed by all personnel. Offerors will be required to propose levels of commitment whether compensated or donated effort, necessary to complete the work described in their proposals. It is expected that realistic levels of effort will be proposed such that an offeror's understanding of the work will be apparent.
In accordance with FAR 52.233-2 SERVICE OF PROTEST (NOV 1988):
(a) Protests, as defined in Section 33.101 of the Federal Acquisition Regulation, that are filed directly with an agency, and copies of any protests that are filed with the General accounting Office (GAO) shall be served on the Contracting Officer (addressed as follows) by obtaining written and dated acknowledgment of receipt from:
Mr. Robert R. Carlsen
Hand-Carried Address:
National Institutes of Health
National Heart, Lung, and Blood Institute
Contracts Operations Branch
II Rockledge Center, Room 6122
6701 Rockledge Drive, MSC 7902
Bethesda, MD 20817U.S. Postal Service:
National Institutes of Health
National Heart, Lung, and Blood Institute
Contracts Operations Branch
II Rockledge Center
6701 Rockledge Drive, MSC 7902
Bethesda, MD 20892-7902
The copy of any protest shall be received in the office designated above within one day of filing a protest with GAO.
Please number each page of text. Type density and size must be 10-12 points. If constant spacing is used, there should be no more than 15 cpi, whereas proportional spacing should provide an average of no more than 15 cpi. There must be no more than six lines of text within a vertical inch.
The technical proposal should be organized as follows:
No Government furnished material, facilities, or equipment are envisioned for this acquisition.
The Government reserves the right to award a contract without discussions if the Contracting Officer determines that the initial prices are fair and reasonable and that discussions are not necessary. If award will be made without conducting discussions, offerors may be given the opportunity to clarify certain aspects of their proposal (e.g., the relevance of an offeror's past performance information and adverse past performance information to which the offeror has not previously had an opportunity to respond) or to resolve minor or clerical errors.
The offeror's business proposal shall include the basic cost/pricing information specified in the Standard RFP Instructions and Provisions, under the Streamlined RFP References Directory referenced in this RFP. In addition, the Government may require offerors included in the competitive range to submit additional information substantiating their proposed costs or prices. This additional cost/pricing information will be requested after establishment of the competitive range, and potentially includes payroll documentation, vendor quotes, invoice prices, and/or any other information deemed necessary by the Contracting Officer to evaluate the reasonableness of the price or to determine cost realism. The information may also include submission and certification of cost or pricing data. If possible, please submit a computer disk with the cost proposal in Excel® format.
It is understood that the acquisition and supply of all human specimen material (including fetal material) used under this contract will be obtained by the Contractor in full compliance with applicable State and Local laws and the provisions of the Uniform Anatomical Gift Act in the United States and that no undue inducements, monetary or otherwise, will be offered to any person to influence their donation of human material.
The contractor shall acknowledge the support of the National Institutes of Health whenever publicizing the work under this contract in any media by including an acknowledgment substantially as follows:
"This project has been funded in whole or in part with Federal funds from the National Institute of Dental and Craniofacial Research, National Institutes of Health, under Contract No. ."
Unless otherwise specified in this contract, the Contractor is encouraged to publish, and make available through accepted channels, the results of its work under this contract. A copy of each article submitted by the Contractor for publication shall be promptly sent to the Project Officer. The Contractor shall also inform the Project Officer when the article or other publication is published, and furnish a copy of it as finally published.
This section identifies the items located in the Streamlined RFP References that are applicable to this Request For Proposal (RFP).
The entire file entitled "STANDARD RFP INSTRUCTIONS AND PROVISIONS" is applicable to this RFP, except as modified by the inclusion of items from the "OPTIONAL RFP INSTRUCTIONS AND PROVISIONS" below.
The following items are applicable from the file entitled "OPTIONAL RFP INSTRUCTIONS AND PROVISIONS". The full text of the provisions is available in the file.
List of provisions which apply to this specific RFP:
The following items are applicable to this specific RFP and are located in the file entitled "FORMS, FORMATS, AND ATTACHMENTS", under Streamlined RFP References:
SUBMIT WITH TECHNICAL PROPOSAL (with original and every copy of technical proposal)
SUBMIT WITH BUSINESS PROPOSAL:
OTHER--TO BE SUBMITTED LATER:
ANTICIPATED TO BE INCLUDED AS CONTRACT ATTACHMENTS:
The "SAMPLE CONTRACT FORMAT-GENERAL" under the Streamlined RFP References is applicable to this RFP. Selected clauses applicable to this acquisition will be included in the contract.