A -- PATHOGEN FUNCTIONAL GENOMICS RESOURCE CENTER DRAFT RFP Reference Number: NIH-NIAID-DMID-01-07 Request for Comments Title: Pathogen Functional Genomics Resource Center Purpose of Announcement The purpose of this announcement is two-fold: first, to inform potentially interested individuals, institutions and organizations of a draft project requirement of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), designed to establish a Pathogen Functional Genomics Resource Center, and second, to solicit comments from interested parties with respect to the scope, design and requirements of this draft solicitation. Please note that proposals are not being solicited at this time. As provided for by FAR 5.205 entitled "Special Situations," a draft project announcement is being broadcast. With this announcement, the NIAID is soliciting comments and recommendations on the entire draft project requirement (i.e. Statement of Work, Technical Evaluation Criteria and Reporting Requirements) in order to: (1) determine interest in this solicitation; (2) assure that requirements included in the documentation will meet the intent of the solicitation; and (3) identify or clarify what may appear to be problems, conflicts, or obstacles for an institution or organization that might otherwise wish to become a potential offeror. Background and Major Components of the Draft Project Requirement A major priority of the NIAID's Division of Microbiology and Infectious Diseases (DMID) is the acceleration of research on microbial pathogens and invertebrate vectors that are responsible for infectious diseases of public health relevance. Automated sequencing technologies, developed in the 1990s, have made possible the complete sequencing of the entire genomes of microorganisms, including a number of important human pathogens. The sequences of hundreds and thousands of new genes are made available weekly either through traditional peer-reviewed publications or through publicly accessible Web sites. The vast majority of these gene sequences are accompanied by "annotation" based solely on computational sequence similarity studies that have divided these genes into completely novel sequences or into putative functional categories based on homology with functionally cloned genes already in established databases. High throughput methods are being developed to systematically and globally analyze gene and protein expression. Access to these methods and related emerging technologies will advance our ability to decode the vast amounts of sequence data. In addition, databases and innovative computational tools are needed to store, access and query the information obtained from these studies. The goal of this contract resource is to address the Institute's desire to make available, to the research community, resources and facilities for the functional analysis of pathogen genomes. This contract resource will be established by the NIAID to acquire and distribute relevant expertise and resources for whole genome expression analysis and related tools and emerging technologies for functional analysis at the whole organism- or genome level. The NIAID intends to review these proposals and to make an award under a cost reimbursement/completion based system where the resource center will be evaluated for: expertise and technical capacity of the personnel, including the ability to select additional subcontractors as needed for emerging technologies soundness of the scientific plan to prioritize needs and to develop, acquire and distribute the necessary technologies plans for dealing with intellectual property issues and procedures that will be used to resolve legal issues that may arise infrastructure, resources and facilities to accomplish the project Once awarded, the progress of the resource center will be determined by completion of goals and milestones, through comments from end-users of the distributed resources and technologies and by an outside advisory panel charged with helping NIAID to oversee progress.. We encourage you to respond to Lawrence M. Butler, NIAID Contracting Officer on this matter using the Response Guidelines provided, to indicate issues or elements you are particularly in favor of, or which you find prohibitive to your group or corporation's response capability. We would be particularly interested in knowing what issues are paramount in your decision-making process concerning this solicitation, and if, after consideration, a "no" decision is reached, why your organization can't or chooses not to respond to the solicitation. Please be as direct as possible. DRAFT PROJECT REQUIREMENT Title: Pathogen Functional Genomics Resource Center Reference Number: NIH-NIAID-DMID-01-07 Introduction The purpose of this contract is to support the Expanded Program on Pathogen Genomics of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH). The goal of this program is to accelerate research for the systematic understanding of the genomic information of microbial pathogens and invertebrate vectors. This program will build upon, and take advantage of, the complete nucleic acid sequences of organisms whose sequences are available in the public domain. The last years of the 20th Century have witnessed the genomics revolution in biology brought about by technological advances in high throughput DNA sequencing and by development of computational methods to handle the large amounts of sequence information. For the first time in history, scientists have access to the complete genetic content of living organisms. At the present time, this revolution may be having its greatest impact in the field of microbiology as the genomes of many bacteria and unicellular eukaryotes have been, or will soon be, completely sequenced. In particular, research on microbial pathogens will benefit dramatically, as opportunities for innovative and efficient approaches to exploring whole organism biology will be provided by the availability of the sequence information. The challenge to investigators is to decode this sequenceinformation by determining its functional significance. It is anticipated that the knowledge gained from such functional analysis will enhance our understanding of pathogenic mechanisms and will lead to the development of improved diagnostics, therapies and preventive strategies. Over the past three years, the NIAID has made a significant contribution to the field of microbial genomics by increasing its support of large-scale sequencing projects. At the current time, the NIAID supports the genomic sequencing of over 20 pathogens responsible for considerable morbidity and mortality (http://www.niaid.nih.gov/dmid/genome.htm). With NIAID support, sequencing of the entire genomes of Mycobacterium tuberculosis, Treponema pallidum and Chlamydia trachomatis as well as one of the chromosomes of the malaria parasite Plasmodium falciparum and of Leishmania major has been completed. With support from other agencies, the genomes of additional human pathogens of interest to NIAID have been, or soon will be, completely sequenced as well. With funding from NIAID and other public agencies, sequence information is made rapidly and freely available, thus benefiting the largest possible number of investigators. These studies have already provided new insights into microbial biology, complexity and diversity. Further, the sequence information has already provided many leads for drug and vaccine discovery and has revealed a number of different mechanisms by which pathogens undergo antigenic variation to evade the host immune response. Remarkably, a large fraction of each organism's genes is unique to that species and of unknown function; i.e. there are no homologous genes in existing databases. The NIAID is committed to extending its support for projects to sequence the genomes of additional organisms, including fungi, protozoan and helminth parasites and invertebrate vectors of infectious agents, and to using the resulting information to better understand and control infectious diseases. The Institute supports a large portfolio of extramural research grants on human pathogens and recognizes that these studies will profit from the sequence information. The Institute also recognizes that rapidly emerging technologies are being developed for functional studies that would greatly facilitate the decoding of the genomic sequence by exploiting methods for whole genome and organism approaches to functional analysis. Evolving approaches that examine global patterns of gene expression will allow for the identification of expressed sequences involved in specific pathogen phenotypes. Methods are also being developed for comparative genome analysis that seek to discover genetic polymorphisms that govern phenotypic differences among different pathogen lines and clones. In addition, new computational tools are needed to enable investigators to store, access and query the sequence and functional data. The proposed contract resource addresses the Institute's need for additional resources and facilities for functional analysis of pathogen genomes. This includes providing 1) molecular reagents derived from large-scale sequencing projects and 2) reagents, facilities and expertise for whole genome expression analysis. Part A describes the current needs of the Division of Microbiology and Infectious Diseases. Part B describes Optional Contract Activities in support of additional efforts which DMID may wish to support in the future; for example, development of relational databases and other bioinformatics tools as well as facilities for whole organism protein expression analysis. When the Government exercises the Optional Contract Activities in Part B, these will be accomplished under a level of effort type contract. Offerors submitting a proposal under this solicitation must prepare a proposal that includes the required work outlined above (Part A) AND the optional contract activities identified in Part B. Within the proposal, each part should be distinct, as each will be subject to its own review criteria. PROPOSALS FOR PART A ALONE OR PART B ALONE SHALL NEITHER BE ACCEPTED NOR CONSIDERED FOR AWARD UNDER THIS SOLICITATION. STATEMENT OF WORK PART A Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities not otherwise provided by the Government under the terms of this contract, directly or through subcontractors and/or consultants, as needed to provide and distribute the resources required for functional genomic analysis of microbial pathogens and invertebrate vectors, under the direction of NIAID staff in consultation with appropriate NIAID advisory groups. (Note 1 TO THE OFFEROR: The Prime contractor is responsible for all work performed under this contract. Because a single institution may not have the expertise and facilities required to perform all requirements of the Statement of Work, subcontracting is permitted. The Offeror shall describe in the technical proposal areas of responsibility of any subcontractor as they pertain to the Work Statement in the same detail as their own proposal. Offerors should describe an administrative framework showing clear lines of authority. Documentation should be provided on the qualifications, experience, education, competence, and availability of the Principal Investigator, Research, Technical and Administrative Support staff. If subcontractors are proposed, similar technical information should also be provided as part of the Technical Proposal. The subcontractors must provide cost details. ) Specifically, the Contractor shall: 1. In Conjunction with the Project officer Establish a Scientific Advisory Committee Composed of Genomics Experts The Contractor shall establish a committee composed of scientists knowledgeable in a broad range of genomics and bioinformatics research areas, including but not limited to molecular and computational biology, high throughput methods for DNA sequencing, oligonucleotide synthesis and Polymerase Chain Reaction, expression array technologies, proteomics, relational databases and Web site development. The committee will provide advice to the Contractor and to the NIAID on the needs of scientific community for reagents and technologies for functional genomics including computational methods. The Contractor, with the approval of the Project Officer, will determine membership of the advisory committee. The Contractor will be responsible for the organization of the meetings of the committee. (Note 2 TO THE OFFEROR: For the purposes of budget planning, the offeror should assume that the advisory committee, composed of ten members, will meet twice per year in the Bethesda, MD area. Travel and per diem for advisory committee members and appropriate representatives from the Contractor should be included in the budget.) 2. Develop Facilities and Resources for Genotyping and Expression Analysis: The Contractor shall develop a resource for the generation of oligonucleotide and/or cDNA microarrays for high throughput genotyping and gene expression analysis. Specifically, the Contractor will: a. Maintain awareness of advances in relevant technologies and develop plans to improve methods applicable to the focus of the Functional Genomics Resource Center. The Contractor should develop appropriate expertise and acquire relevant equipment in: 1) preparing arrays using state of the art technologies ("spotting" amplicons; photolithographic synthesis; etc.); 2) preparing test RNA and/or DNA for hybridization; and 3) reading and interpreting the results of array experiments. b. Provide facilities for utilizing the arrays in hybridization assays for genotyping organism polymorphism and/or RNA expression analyses. c. Validate the results of array experiments (e.g. by re-sequencing clones for polymorphism studies; by comparing expression results with Northern blot analyses; by establishing reproducibility of results). d. Implement or develop pattern recognition algorithms as well as other computational tools, including databases, for organizing, displaying and analyzing the results of array experiments.e. Display results of array experiments on a publicly accessible Web site, under policies developed with the advice of the external advisory committee and approved by the project officer. (Note 3 TO THE OFFEROR: For the purpose of preparing a cost estimate, assume that cDNA expression arrays will be generated for two completely sequenced pathogens in the first year and three additional pathogens each year thereafter. The Contractor should indicate equipment currently available and the expertise of personnel engaged in these experiments.) 3. Transfer Array Technologies to Pathogen Research Community a. Develop a plan for distributing arrays and validated protocols to research investigators capable of conducting experiments at their own institutions. b. Make available to the research community computational tools to analyze the results of array experiments. c. Provide technical support on array technologies, including conducting workshops. d. Develop a plan for conducting array experiments using material submitted by investigators and for making the results publicly available under approved policies. (Note 4 TO THE OFFEROR: For the purposes of preparing a cost estimate, assume that twenty expression array experiments will be conducted for each available genome per year using material (RNA) submitted by extramural investigators. 4. Acquire, and Produce/Expand (as necessary) Reagents: The Contractor shall acquire reagents after receiving approval by the Project officer. The Contractor shall actively and independently identify reagents that have been used in, or developed from, large-scale pathogen genome sequencing projects. The acquisition of reagents, either by purchase or donation, shall be an ongoing activity. Reagents purchased shall be acquired through a competitive process when practical in accordance with FAR Part 13 Small Purchase Procedures and also in accordance with the prior consent requirements of FAR Part 44. The Contractor shall keep proper documentation on file supporting: (1) the price reasonableness for all acquisitions; and (2) the criteria for evaluation of all sources for reagent acquisitions. The Contractor shall produce reagents as needed after receiving approval by the Project Officer. Production of reagents includes expansion of renewable reagents, including microbial cultures and recombinant DNA. For the purposes of this contract, reagents may include but are not limited to the following biological materials: Microbial strains, clones or isolates used a source (type organism) for large-scale genome sequencing projects; Genomic DNA prepared from the type organisms; Libraries ("shotgun", genomic DNA, cDNA) used in large-scale genome sequencing projects; Sets of plasmids covering the entire genome or chromosome; Sets of unique oligonucleotide PCR primers and/or amplicons corresponding to open reading frames identified in the large-scale genome-sequencing project or to cDNA clones. The list provided is for illustrative purposes and is not comprehensive. The selected contractor will continue to identify and recommend new sources of reagents throughout the term of this contract. A detailed plan for identifying, prioritizing and acquiring reagents in each of the categories listed above as well as the offeror's knowledge, experience and qualifications must be submitted as part of the Technical Proposal. (Note 5 TO THE OFFEROR: It is anticipated that a number of reagents (especially microorganisms and libraries) will be donated from the centers responsible for sequencing the genomes; all other "acquisition" of reagents may be accomplished through purchase and/or services. This includes purchase orders/subcontracts for producing reagents, expansion of reagents (renewable of reagents provided to the Contractor in small amounts that will require expansion) and quality control analyses of reagents. For any proposed subcontractor(s) to produce/expand reagents similar technical information shall be provided as part of the proposal as that required from the Prime Contractor, i.e. technical approach, methods, knowledge, experience, qualifications, facilities, resources, etc. Cost details shall also be provided by the subcontractor and submitted with the Business Proposal. For budget planning purposes, assume acquisition of reagents for three (3) completely sequenced genomes or chromosomes per year totaling 10 Megabases (Mb) and assume one (1) open reading frame per Kilobase (Kb). A listing of NIAID supported microbial genome projects is available at http://www.niaid.nih.gov/dmid/genome.htm.) The handling and transportation of all reagents and Government-owned property under this Contract shall be in accordance with all applicable local, state and Federal regulations including safety controls and standards. Details on health and safety standards are available on request. (NOTE 6 TO THE OFERROR: The offeror must demonstrate awareness of federal rules established for the Facilities Transferring or Receiving Select Agents as indicated in Final Rule 42CFR 72 (http://www.cdc.gov/od/ohs/lrsat/42cfr72.htm).) (Note 7 TO THE OFFEROR: If the offeror is a commercial firm, the offeror must address in detail in the Technical Proposal how potential conflicts of interest will be resolved between commercial acquisition and distribution of reagents and the Functional Genomics Resource Center acquisition Posted 12/10/99 (W-SN407572).

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