MODIFICATION
B -- LABORATORY TESTING
- Notice Date
- 6/13/2016
- Notice Type
- Modification/Amendment
- NAICS
- 541380
— Testing Laboratories
- Contracting Office
- Department of Health and Human Services, National Institutes of Health, National Institute of Child Health and Human Development, Contracts Management Branch, 6710B Rockledge Dr., Suite 1124, MSC7000, Bethesda, Maryland, 20892-7510, United States
- ZIP Code
- 20892-7510
- Solicitation Number
- NICHD-16-052-1
- Archive Date
- 7/21/2016
- Point of Contact
- Patricia Haun, Phone: 301-443-7786
- E-Mail Address
-
haunp@mail.nih.gov
(haunp@mail.nih.gov)
- Small Business Set-Aside
- N/A
- Description
- THE PERIOD OF PERFORMANCE IS EXPECTED TO LAST 12 MONTHS This is a combined synopsis/solicitation for commercial items prepared in accordance with the format in FAR 12.6 as supplemented with additional information included in this notice. This announcement constitutes the only solicitation and a separate written solicitation will not be issued. This solicitation number is NIH-NICHD-16-052-1 and is issued as a Request for Proposal (RFP). The solicitation/contract will include all applicable provisions and clauses in effect through Federal Acquisition Circular 2005-88. The North American Industry Classification (NAICS) Code is 541380 and the business size standard is $15M. However, this solicitation is not set aside for small business. This acquisition is being conducted using Simplified Acquisition Procedures in accordance with FAR Part 13. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is requesting qualified Contractors that can provide hCPE ΔN Replication of Data. The NICHD DIR is seeking a scientific group to replicate a series of experiments to address the existence of hCPE ΔN, the human carboxypeptidase gene, and to provide data that replicates both published and of unpublished data. Background: A variant mRNA transcript of the human carboxypeptidase E (hCPE) gene has been described in the literature, as a splice variant with a deletion of 98 bases in exon 1, termed CPE deltaN (Lee et al., J Clinical Investigation, 2011). The presumed splicing does not conform to a canonical splicing mechanism. It has been described as a splice variant that only exists in cancer cells and cancer tissues prone to metastasis. It was proposed that the CPE deltaN transcript encodes a novel 40 kDa CPE protein in the cytosol of cancer cells (Lee et al) and is reported to be then directed to the nucleus where it activates metastatic genes through the regulation of histone deacetylase enzymes (Lee et al). The conclusion of the report is that the presence and measurement of the mRNA for hCPE deltaN can be used as a clinical biomarker for the prediction of metastatic potential of several cancers in humans. Recent evidence (unpublished) has suggested that the CPE deltaN splice variant is an artifact of the reverse transcription (RT) step and/or the PCR step leading to the possibility that hCPE deltaN may not exist naturally but that it is generated from the WT hCPE sequence. The possible reason for this lies in the unusually high G/C content of the hCPE gene (~80-85%) where the deltaN deletion has been reported to occur in exon 1. This region may form complex secondary structures that would be difficult for polymerases to read through accurately using standard conditions. In addition this region (exon 1) has multiple micro-homology domains within it giving rise to possible RT and PCR artifacts (See Appendix I). Also, the 40 kDa hCPE deltaN protein is not predicted to be generated from the mRNA transcript (See Appendix II). Applicants to undertake this project will have expertise in cancer genetics research and a track record of expertise and publications in the areas of cancer metastasis. The scope of work will require bioinformatics analysis, quantitative RT-PCR, primer sequencing, and cloning, as well as Northern and Western blots. SCOPE OF WORK: Four specific aims are to be addressed: Specific Aims: 1. Demonstrate that the primers, described as specific for hCPE deltaN and used in Lee et al. (J Clinical Investigation, 2011), are specific for hCPE deltaN and cannot (or can) cross-prime the WT sequence. Bioinformatic analysis of the primer sequences should be included. As controls, reagents such as the plasmids containing the ORF of WT hCPE and the ORF of the proposed hCPE deltaN (and empty vector) are available from the NICHD. All reagents received should be sequenced to confirm their accuracy prior to use and used in serial dilutions as template for PCR or transfected into a cell line and analyzed by the quantitative RT-PCR procedure described in the original paper. 2. Clone any human CPE mRNA transcripts from hepatocellular carcinoma (HCC) tissue and/or MHCC97 cell lines (high and low metastatic phenotype, MHCC97H, MHCC97L) as these were reported to contain CPE deltaN in the original Lee at al. paper and recently in Huang et al., Tumor Biology, 2016; see also Tumor Biology, Zhou et al., 2013. For consistency and reproducibility, the colon cancer cell lines, SW480 and HT-29, should also be analyzed in parallel as they were reported in the Lee et al. paper (low and high metastatic phenotype). These cell lines can be obtained from NICHD. Use of the Ambion FirstChoice RLM-RACE kit (or equivalent) is preferred because it favors transcripts with a 5'CAP, indicative of a naturally occurring mature RNA transcript. Touch-down PCR should be employed to minimize artifacts. It is expected that standard PCR cycle numbers will be used in the 5'-RACE cloning, but to test for the presence of rare transcripts, increased cycle numbers and/or nested PCR may be appropriate. If required, however, the relevance of the rarity should be noted. Sequence all products cloned using high stringency for the sequencing procedure because the G/C content in this region is very high and may cause mis-reads. 3. Perform Western blot analysis on HCC cancer tissue and/or MHCC97L and MHCC97H cell lysates for the detection of any CPE protein. hCPE deltaN protein has been reported in these cells as a 40 kDa protein (Lee et al). Analysis should be on total soluble cell lysate (as in Lee at al.) and on nuclear versus cytosolic fractions. Use of an endocrine cell line that contains CPE should be used as a control for the extraction procedures and as a positive control for the Western blot, e.g., AtT20 cells, a mouse corticotroph cell line. At least two unique anti-CPE antisera should be used, i.e., antibodies made against different antigenic sources and made in two different hosts (rabbit, mouse, goat). It is not recommended to use the BD Bioscience monoclonal anti-CPE antibody, which can give non-specific bands at 40kDa. If used, it should be as a third antibody with all controls (omission of primary antibody, use of an absorption control where possible). Use of siRNA oligos transfections to reduce endogenous CPE is highly recommended to demonstrate specificity. Stealth siRNA oligos specific for hCPE are available from NICHD. 4. A Northern blot on HCC and CRC cell lines using standard procedures. A new semi-quantitative RT-PCR assay has been developed to identify and measure hCPE deltaN in cell lines and cancer tissues (see Appendix III for primer sequence and cycle conditions). An independent bioinformatic analysis of the primer sequences should be included in the report. Using these primers and conditions, confirm the presence of hCPE deltaN in HCC tissue and/or MHCC97L and MHCC97H cells using standard RT-PCR molecular biology procedures. In parallel, perform an identical analysis using the following modifications that are incorporated to minimize artifacts of the RT. After denaturation of the RNA template at >65 C (in the presence of the random primers), the RNA is to be cooled directly to 50 C to prevent refolding and a thermostable RT enzyme used (optimum temperature ~50 C). In addition, to minimize artifacts of the PCR, perform the annealing temperature at 65 C instead of 60 C. Compare and contrast the different procedures to identify if bands are reduced or eliminated when more stringent conditions are used. Confirm the identity of each PCR product by sequencing (which will be provided at a later time). A. EVALUATION FACTORS General Offerors are advised that an award under this solicitation shall be made to the Offeror whose proposal is determined by the Government to represent the best value to meet the Government's needs. The Technical Proposal shall receive paramount consideration in the selection of the Offeror for this acquisition. All evaluation factors, other than cost or price, when combined are significantly more important than cost or price. However, cost or price may become a critical factor in source selection in the event that two or more Offerors are determined to be essentially equal following the evaluation of all factors other than cost or price. In any event, The Government reserves the right to make an award to the Offeror whose proposal provides the best value to the Government. Best value means the expected outcome of an acquisition that, in the Government's estimation, provides the greatest benefit in response to the requirement. The technical evaluation shall be based on the demonstrated capabilities of the Vendor set forth in the Technical Proposal. The Government reserves the right to make an award without discussions if overall best value can be clearly determined and if no other Offeror would have a reasonable chance at award if discussions were conducted. Offerors shall be evaluated in accordance with the factors set forth below. Sub-factors listed under each factor are of equal importance to each other. The criteria below are listed in the order of relative importance with weights assigned for evaluation purposes. 1. Understanding the Requirement (Technical and Management Approach) 50 Points A. Technical Approach (40 Points) a. Understanding and approach to supporting the technical task (aims) as identified in the Statement of Work. b. Specific methods and techniques to be employed with respect to these tasks (aims). c. Knowledge of the applicable technology to be used as described in the Statement of Work. d. Knowledge and experience with the business processes describing the suitability of the offeror (please provide a bibliography of publicationsrelevant to the research). 2. Management Approach (20 Points) a. Thorough and effective plan or the conduct of the task (aims) activities. b. Appropriate organization and allocation of personnel and resources needed to conduct the tasks (aims) outlined in the Statement of Work, including the methods for interaction and communication with the scientific, technical and administrative staff of NICHD. 3. Qualifications (40 Points) A. Key Personnel (30 Points) a. Quality, depth and recent experience, education and training of the individual personnel to be assigned to the project. b. Successful performance of tasks similar to the tasks described in the Statement of Work. c. Ability to supply subject matter experts across the entire range of requirements if and as needed over the performance period. 4. Past Performance and Organizational Experience (10 Points) a. Organization's history of successful completion of projects of similar nature, including the quality of technical performance and adherence to schedule and cost/price. b. Organization's past performance with projects and availability of facilities and equipment appropriate to the project in supporting biomedical research. B. COST/PRICE EVALUATION Offeror proposed price shall be evaluated on realism and reasonable for the Government to purchase the equipment. For a price to be reasonable, it must represent a price to the government that a prudent person would pay when consideration is given to prices in the market. Normally, price reasonableness is established through adequate price competition, but may also be determined through cost and price analysis techniques as described in FAR 15.404. Realism will be evaluated only on the offeror(s) inputs which the Government will use to determine the most probable cost/price for the equipment in a manner consistent with the offeror's proposal. Cost/Price realism analysis will be conducted in accordance with FAR 15.404-1(d). The result of the cost/price realism analysis will be considered in the making the best value tradeoff decision. C. ADDITIONAL EVALUATION FACTORS (These factors will not be evaluated ) Past Performance The Government will evaluate the quality of the offeror's past performance based on information obtained from references provided by the offeror, as well as other relevant past performance information obtained from other sources known to the Government. Evaluation of past performance will be a subjective assessment based on consideration of all relevant facts and circumstances. It will not be based on absolute standards of acceptable performance. The Government is seeking to determine whether the offeror has consistently demonstrated a commitment to customer satisfaction and timely delivery of services at fair and reasonable prices. The assessment of the offeror's past performance will be used as a means of evaluating the capability of the offeror. Thus, an offeror with an exceptional record of past performance may receive a more favorable evaluation than if it has an acceptable record. Past performance will not be scored, but the Government's conclusions about overall quality of the offeror's past performance will be influential in determining the merits of the offeror's proposal and in selecting the offeror whose proposal is considered most advantageous to the Government. By past performance, the Government means the offeror's record of conforming to ns and to standards of good workmanship; the offeror's record of forecasting and controlling costs; the offeror's adherence to contract schedules, including the administrative aspects of performance; the offeror's reputation for reasonable and cooperative behavior and commitment to customer satisfaction; and generally, the Offeror's business-like concern for the interest of the customer. The Government will consider the number or severity of an offeror's problems, the effectiveness of corrective actions taken, the offeror's overall work record, and the age and relevance of past performance information. The lack of a performance record may result in an unknown performance risk assessment, which will neither be used to the advantage or disadvantage of the offeror. D. BUSINESS PROPOSAL INSTRUCTIONS Proposals should not exceed ten pages and should include: 1. Personnel charges, broken down by role (PI, postdoctoral fellow, technician, as applicable) and prorated for the period of performance 2. Research materials, itemized 3. Equipment usage charges, as applicable 4. Overhead charges For quotation purposes and information only: Provided as a resource and assisting with proposal preparation, vendors are advised that based on Market Research and Historical Information, the range of hours needed to fulfill the requirements based on expertise and experience for the 12 month period is as follows: CATEGORY LABOR HOURS Principal Investigator 260 Staff Scientist 260 Post-Doctoral Fellows (2) 520 Each Technician 520 E. DELIVERABLES Length: A report summarizing key findings, together with Appendices providing full experimental data and results and describing methodology followed are required. F. QUESTIONS AND RESPONSES TO THE RFQ All questions regarding this solicitation must be submitted electronically (via email) to Ms. Patricia Haun at haunp@mail.nih.gov no later than 3:00 PM, ET, on May 24, 2016. Please reference the specific area of the RFQ letter or attachment when asking a question(s). Responses to all relevant questions of clarifications and/or ambiguities shall be addressed and forwarded electronically by an Amendment to the solicitation no later than, 3:00 PM, ET, on May 25, 2016. If this solicitation is amended, all terms and conditions that are not amended, shall remain unchanged and in full force and effect. Interested vendors capable of furnishing the government with the services specified in this synopsis should submit a copy of their proposal via email to haunp@mail.nih.gov. Quotations will be due fifteen (15) calendar days from the publication date of this synopsis or by July 6, 2016 by 3:00pm EST. via email. The quotation must reference "Solicitation number" NIH-NICHD-16-052-1. Note: In order to receive an award, contractor must be registered and have valid certification in the SAM database @www.sam.gov. Added: <input type="hidden" name="dnf_class_values[procurement_notice][description][1][added_on]" value="2016-06-03 14:02:47">Jun 03, 2016 2:02 pm Modified: <input type="hidden" name="dnf_class_values[procurement_notice][description][1][modified_on]" value="2016-06-13 14:34:20">Jun 13, 2016 2:34 pm Track Changes THE PERIOD OF PERFORMANCE IS EXPECTED TO LAST 12 MONTHS THIS IS BEING AMENDED TO EXTEND THE CLOSING DATE TO JULY 6, 2016
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