Structural Genomics Centers for Infectious Diseases

Introduction The National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH), Department of Health and Human Services (DHHS) supports research related to the basic understanding, treatment and ultimately prevention of infectious, immune-mediated and allergic diseases that threaten millions of human lives. The NIAID Division of Microbiology and Infectious Diseases (DMID) supports a comprehensive extramural research program focused on the prevention and control of diseases caused by virtually all infectious agents (with the exception of the Human Immunodeficiency Virus). This includes basic research, such as studies of microbial biology and physiology; applied research, including the development of medical diagnostics, therapeutics and vaccines; and clinical trials to evaluate experimental drugs and vaccines. Description The NIAID has made a significant investment in genomic-related activities that provide comprehensive genomic, functional genomic, bioinformatics, proteomic, and systems biology resources to the scientific community for basic and applied research to rapidly address the Institute's mission and the Nation's biodefense needs (http://www.niaid.nih.gov/topics/pathogengenomics/pages/relatedinitiatives.aspx). The NIAID-supported genomics programs and activities include: - Genome Sequencing Centers, which provide rapid and cost-efficient production of high-quality genome sequences of human pathogens and invertebrate vectors of diseases and human and microbial genotyping. - Bioinformatics Resource Centers, which collect, integrate and provide open access to research data of microbial organisms and vectors of infectious diseases; develop and share open source software tools; and provide bioinformatics services and training to the scientific community. - Structural Genomics Centers for Infectious Diseases, which experimentally characterize the three-dimensional atomic structure of proteins of pathogenic organisms. - Functional Genomics Centers, which apply state-of-the-art technologies to determine the biochemical and physiological roles of uncharacterized genes including hypothetical genes, unknown open reading frames, and noncoding RNAs. - Systems Biology for Infectious Diseases Centers, which identify and analyze the molecular interaction networks of microbial pathogens and their host cells through a combination of computational and experimental high-throughput technologies. - An Integrated Approach to Understanding Host-Pathogen Interactions, the goal of which is to generate a diversity of experimental data through multiple high-throughput "-omics" technologies, with the goal to develop and/or validate computational models of host- pathogen molecular interaction networks and pathways through the analysis and integration of the experimental datasets generated by the high-throughput technologies. These genomics programs have not only provided the scientific community with valuable research resources, but have also enhanced the NIAID's research efforts in a number of areas including pathogen identification, investigation of pathogen virulence mechanisms, and drug and diagnostics development. Projects within these programs have utilized high-throughput technologies to investigate the genome, transcriptome, proteome, or metabolome of a living organism, either as independent entities or as highly interrelated and interdependent components of biological systems. To build upon the objectives of the NIAID Genomics programs and continue to address the Institute's need to further expand the knowledge of the proteome of microbes and the understanding of functional roles of proteins in biological systems, and to support structure-guided design and discovery of new vaccines and therapeutics against infectious diseases, NIAID is re-competing the Structural Genomics Centers for Infectious Diseases program, herein referred to as the Structural Genomics Centers for Infectious Diseases (SGCID) program. In 2007, the NIAID established two five-year contracts to support the SGCID program. These SGCID centers focused on determining three-dimensional (3D) structures of protein targets of biomedical interest. The targets' 3D structure information, as well as the expression clones and peptide materials for thousands of protein targets are made available to the scientific community. The SGCID program was re-competed in 2012 and two five-year contracts were awarded to (http://www.niaid.nih.gov/labsandresources/resources/dmid/sg/Pages/default.aspx): 1. SSGCID: Seattle Structural Genomics Center for Infectious Diseases (Contract No. HHSN272201200025C) 2. CSGID: Center for Structural Genomics for Infectious Diseases (Contract No. HHSN272201200026C) To date, this program has determined more than 1559 3D structures of protein targets of biomedical interest from bacterial, viral, and eukaryotic pathogens. The solved protein structures are instrumental in gaining new insights into protein binding domains and functions of unknown and known proteins. The determination of the structures of proteins involved in a specific biological system and process has revolutionized views of the biological system architecture, expanded understanding of proteins' functional roles, and opened up new avenues of research. Both SGCID centers have been utilizing small molecule/ligand screening to increase crystallization success rate and to gain functional insight through the newly observed protein-ligand interactions. The targets' 3D structure information, as well as the expression clones and peptide materials for thousands of protein targets are made freely available to the scientific community. Importantly, these SGCID centers have also been providing a 3D structure determination service to the scientific community and more than 896 experimental 3D structures were solved for targets requested from the community. The functional projects have led to collaboration with experimental laboratories who used the three-dimensional protein structures to better characterize the function of the target protein, to explain the ligand-binding activities identified during pilot screening, or to design a more effective immunogen. These SGCID Centers have provided unique structural biology resources for investigators focused on basic research as well as discovery and development of therapeutics and vaccines for infectious diseases. For example, the solved structures of several proteins in complexes have led to follow-up drug discovery efforts funded by Gates Foundation, including mycobacterial apartyl-tRNA synthetase, an enzyme genetically identified to be involved in the resistance of Mycobaterium tuberculosis (Mtb) to drugs, FadD32 from Mtb, the enzyme that catalyzes the penultimate step in mycolic acid biosynthesis and whose inhibition is lethal for Mtb, and Plasmodium falciparum Prolyl-tRNA synthetase. The goal of the SGCID program is to continue the experimental determination of 3D atomic structures of proteins and other molecules with an important biological role in human pathogens themselves, or molecules involved in host-pathogen interactions, by applying state-of-the art high-throughput (HTP) technologies and methodologies. Pathogens include those included on the NIAID Category A-C Priority Pathogen lists and organisms causing emerging and re-emerging infectious diseases (http://www.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/research/Pages/CatA.aspx). This program will also support research projects that utilize experimental approaches to better characterize the molecular mechanisms of protein targets and gain further insight into the functional roles of these targets. The knowledge of the 3D structures and molecular functions of protein targets will provide: 1) a structural view of biological processes and pathways to assist investigation at the systems level; and 2) insights into the target functional mechanisms, in interaction with other biological molecules or with synthetic compounds. In addition, this program will support projects that perform structure-guided vaccine design and drug discovery, and conduct evaluation and validation of the underlying mechanism of action required for therapeutic use against infectious diseases. The structure-guided approach will provide improved selectivity, specificity and optimization of drug and vaccine identification and development in a rational way. The 3D structure information, reagents including expression clones and purified proteins, and services provided by the SGCID centers will be made freely available to the broad scientific community. The purpose of this contract is to provide scientific support to the SGCID through a) Generation of 3D structures for targets derived from bacterial, viral, eukaryotic and other human pathogens using HTP technologies and methodologies; b) Conduct of studies to characterize molecular functions and biochemical properties of selected targets; c) Conduct of studies for structure-guided design and functional evaluation of drug targets and vaccine candidates; d) Provision of a 3D structure determination service to the external scientific community; and e) Dissemination of contract generated resources, including all 3D structure information and reagents. It is anticipated that one or more cost reimbursement, level of effort type contracts will be awarded with a one-year base period of performance beginning on or around June 1, 2017. Awards are expected to include 4 one-year option periods. The total period of performance, including options, is five years. The Government's base level of effort requirement is estimated at 35,360 labor hours for each contract year, equating to 17 FTE's with an FTE being defined as 2,080 hours. In addition to the base level of effort, each year of performance is anticipated to contain an option quantity for up to 6 additional FTEs. Any responsible offeror may submit a proposal which will be considered by the Agency. This RFP will be available electronically on/about May 25, 2016, and may be accessed through FedBizOpps http://www.fedbizopps.gov/. This notice does not commit the Government to award a contract. No collect calls will be accepted. No facsimile transmissions will be accepted. For this solicitation, the NIAID requires proposals to be submitted via the NIAID electronic Contract Proposal Submission (eCPS) website. Submission of proposals by facsimile or e-mail is not acceptable. For directions on using eCPS, go to the website https://ecps.nih.gov/NIAID/home/howto and then click on "How to Submit."