Attachment 1 - FFRDC Draft Statement of Work.docx

*** SOURCE SELECTION INFORMATION SEE FAR 2.101 3.104 ***

Contents

National Mission Programs………………………………………………………….……………………………….. 8

Animal Sciences………………………………………………………………………………………………………………….……..17 Assay Development and Performance 20 Pharmacodynamics and Pharmacokinetics ………………………………………………………………………..20 Metabolic Epidemiology 21

CLIA Laboratories 21 Molecular Diagnostic Laboratory.……………………………………………………………………………………………...21 Clinical Diagnostic Laboratory………………………………………………………………………………………….…………22 Biomarker Reference Standards Laboratory…………………………………………………………………….…………22

Information Technology Infrastructure and Operations Management………………………….32

End-user Support…………………………………………………….………………………………………………………………..35 Unified Communications and Audiovisual Services…………………………………………………………………...35 Infrastructure Support……………………………………………………………………………………………………………...35

Proteomic Data Management………………………………………………..……………………………………42

I BACKGROUND

What is a Federally Funded Research and Development Center (FFRDC)?

Federally Funded Research and Development Centers (FFRDC) enable agencies to use private sector resources to accomplish tasks that are integral to the mission and operation of the sponsoring agency. As described in the Federal Acquisition Regulation (FAR), an FFRDC meets a “special long‐term research and development need which cannot be met as effectively by existing in‐house or contractor resources” (FAR 35.017 (a)(2). An FFRDC is required to operate in the public interest, be free from organizational conflicts of interest, provide full disclosure of its affairs to the sponsoring agency and conduct its business in a manner that is consistent with its special relationship with the Government. Furthermore, FAR 35.017 (a)(3) states that “An FFRDC is operated, managed, and/or administered by either a university or consortium of universities, other not-for-profit or nonprofit organization, or an industrial firm as an autonomous organization or as an identifiable separate operating unit of a parent organization.”

The National Cancer Institute (NCI) within the Department of Health and Human Services (HHS) is the sponsoring agency for the Frederick National Laboratory for Cancer Research (FNLCR), the only FFRDC within the government devoted solely to biomedical research. The FNLCR supports the NCI’s mission to lead, conduct, and support cancer research across the nation to advance scientific knowledge and help all people live longer, healthier lives. The FNLCR conducts Government approved research and research support for not only NCI Laboratories and Programs, but also a wide cadre of additional National Institute of Health Institutes/Centers (ICs), most notably the National Institute of Allergy and Infectious Diseases (NIAID), as well as other government agencies.

NOTE: Unless otherwise noted, reference of “NCI” in this Statement of Work (SOW) is not meant to exclude the involvement of other ICs.

The FNLCR serves as a unique, collaborative research and development resource to tackle difficult, urgent and intractable problems that span from basic research to clinical investigations. The FFRDC is at the forefront of developing and adapting new technologies and translating basic scientific discoveries into novel agents/approaches/devices for the prevention, diagnosis and treatment of cancer and other diseases, including the Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS), SARS-Cov-2 as well as emerging diseases. All government agency sponsored work must be within the purpose and mission of the FNLCR.

The FFRDC Program requirements are executed through the FNLCR, which operates as a Government‐owned, Contractor‐operated (GOCO) facility. The facility’s current requirements necessitate complex program/project management coordination. As part of the Contractor’s stewardship of the National Laboratory, it is expected that the Contractor maintain relationships with the broader research community to enhance the intellectual vitality and research relevance of the FNLCR; and to bring the best possible capabilities forward through partnerships, as they pertain to the FNLCR’s mission needs. The Contractor shall actively develop and pursue collaborative engagement with public and private partners to address urgent needs in biomedical research towards the goals of discovery, innovation and the overall improvement of human health. The Contractor shall work with public, academic and private organizations utilizing multiple partnering vehicles to advance scientific discovery and the mission of the FNLCR.

The Contractor shall be responsible for developing and implementing innovative approaches and adopting practices that foster continuous improvement in accomplishing the mission of the FFRDC. The Government expects the Contractor to employ effective, efficient, flexible and responsive management structures, systems, and operations that maintain high levels of quality, safety and security in accomplishing the work required under this Contract. To the extent practicable and appropriate, the Contractor shall rely on national, commercial and industrial standards that can be verified and certified by independent, nationally recognized experts and other independent reviewers.

The Contractor shall ensure compliance with all Standards, Policies, Regulations, Licenses, Certifications and Accreditations as required by the Government in the contract.

Legislative Authority

In 1972, the Frederick Cancer Research Center (FCRC) began operations under the authority of The National Cancer Act of 1971. The National Science Foundation (NSF) notified the NIH that the FCRC was officially designated as an FFRDC in 1975. In 2012 the FFRDC was designated as a National Laboratory now known as the FNLCR. It is a GOCO research facility sponsored by the NCI through the Department of Health and Human Services, in accordance with Federal Acquisition Regulation (FAR) 35.017. Under this authority, the FFRDC undergoes a periodic review for continuance every 5 years as an on‐going program. NCI manages, administers, monitors and is responsible for the overall operation and use of the FFRDC.

II FFRDC VISION, GOALS, AND STRATEGIC PROGRAM OBJECTIVES

FFRDC Vision and Goals

Vision Innovation is an active process and requires institutional resources and commitment of staff at various levels to achieve progress. In accordance with FAR 35.017, the FFRDC must maintain its expertise, preserve familiarity with the needs of the its sponsoring agency, the needs of other stakeholders, and provide rapid response to those needs.

Vision for the FFRDC is:

· A resource to support the intramural and extramural components of the NCI/NIH

· A hub for technology development

· A nucleus for large scale projects which cannot easily be performed elsewhere or through other mechanisms All FFRDC activities and initiatives, independent of which NIH Institute or Center (IC) or other federal agency instigates the work, need to align with the NCI mission and FFRDC vision outlined with this SOW.

Goals and Operating Principles All aspects of the SOW shall be performed by applying the following goals and operating principles:

· Respond to emergent health crises swiftly and effectively

· Generate novel scientific solutions to complex scientific problems and national mission initiatives commensurate with those of an FFRDC

· Provide exemplary leadership to address challenging scientific questions and the urgent needs of the government.

· Integrate scientific, business and facility elements at all organizational levels, in a highly dynamic environment, to provide unique, high quality results with agility and speed

· Develop and provide strong technical skills for sustaining initiatives and delivering cutting-edge support

· Pursue high risk/high reward projects, including emerging technologies and pilot studies in related fields

· Demonstrate boldness and creativity in ideas and execution

· Maintain a full intellectual, scientific partnership with the NIH emphasizing bidirectional communication at all levels

· Foster cordial collaboration, trusting relationships, and coordinated effort within the FNLCR and with Government stakeholders

· Build relational bridges and work as a team for shared success

· Nurture a spirit of organizational excellence

· Operate in a flexible, transparent, accountable and effective manner, with processes that clearly define roles, responsibilities, and decision-making within the Contractor organization

· Exhibit robust financial tracking, cost control, and the utmost financial transparency in order to operate in the public’s best interest and have full disclosure of its affairs to the Government

· Demonstrate effective operational efficiencies in all areas including, but not limited to, subcontracting, human resources, project management and administrative activities

· Reduce bureaucracy and administrative burden, breakdown logistical barriers and silos

· Identify and implement best approaches to meet the scientific and/or business objectives, and share best practices within the organization

· Anticipate challenges and propose/implement solutions

· Demonstrate flexibility and responsiveness to shifting priorities

· Recruit both long-term and short-term staff in a timely manner

· Match the appropriate skill set and level of expertise to each unique project

· Retain talent and offer training opportunities

· Remain free from organizational and individual conflicts of interest

· Recognize the collective mission at the forefront of all endeavors Strategic Program Objectives The future NCI strategic program objectives for the FNLCR include: 1) national mission programs; 2) basic, translational and clinical research in support of NCI; and 3) core research support services for the entire NCI research community. The Contractor shall adhere to these three facets, which broadly encompass the wide range of NCI’s biomedical research and research support work that is performed at the FNLCR. In all cases, this work is performed in the nature of an FFRDC--flexibly, expeditiously and creatively. Moreover, success within these program areas will require a broad range of expertise in many technical disciplines.

National Mission Programs In 2011, a then NCI Director, Harold Varmus, established an advisory committee that recommended the FNLCR identify and undertake important and ambitious projects in cancer research that would be difficult to pursue without an orchestrated effort, deemed “National Mission Programs.” The models of these novel programs have varied according to the research objective. The first National Mission Program, the RAS Initiative, was launched in 2013 to pursue innovative approaches to attack proteins encoded by mutant RAS genes. The Initiative was built on a hub and spoke model with central projects conducted at FNLCR and collaborative “spoke” projects with other government agencies, biotech and pharmaceutical companies, non-profit organizations, and academic extramural researchers. A second example is the National Cryo-EM Facility, a state-of-the-art facility offering the extramural community free data collection, new platforms and workflows to accelerate the development of next-generation tools for structural determination. Another program effort launched is the response to the COVID-19 pandemic, the NCI’s Serological Sciences Activities, SeroAct. The FNLCR components of SeroAct includes the Clinical Translational Serology and components of Serological Sciences Network, SeroNet. The objective of the Clinical Translational Serology is to catalyze translation of research tools and findings into public health changes that bring together and engage various government organizations, academics, and industry partners that can provide relevant information on public health for decision makers to manage the current and future status of the COVID-19 pandemic. The SeroNet’s objective is to support a broad range of serological sciences research to advance our understanding of all aspects of the immune response to SARS-CoV-2. This will be accomplished by; 1) the expansion of the FNL’s serology laboratory for commercial assay testing and establishment of the national reference standards and reagents and 2) creations of the coordination center that provides overarching technical project management of the following activities, capacity building serological testing centers, and the serological sciences centers of excellences extramural grantees of SeroNet.

Despite the varying operational models, the FNLCR components serve a crucial niche and the staff shall possess professional and high-quality technical expertise to conduct hypothesis-driven research--independently or as part of collaborative teams.

Basic, Translational, and Clinical Research The FNLCR’s work covers a wide range of research from bench to bedside and addresses the needs of the global patient population and researchers nationwide. FNLCR scientists support National Institutes of Health (NIH) led extramural and intramural research programs in areas of basic, translational, and clinical research both at NCI Frederick/NIH and at remote locations. Programs focus in such areas of research into basic disease mechanisms, new treatment modalities, assay and technology development, vaccine and biological development, and clinical trials, to name a few. NCI research objectives are met with either FNLCR staff or subcontract, depending on program needs and requirements. Because the research is largely hypothesis driven, mission critical and/or investigator initiated, the quality of the staff is crucial. As such, the Contractor shall provide talented junior technical staff all the way through senior level scientific staff who are able to form effective intellectual partnerships with government stakeholders and collaborators. Senior staff should be experts within their domains and all staff should strive for continuous learning and engagement.

Core Research Services The third program objective entails cutting-edge research support activities, as well as enhancing existing technologies. Core Research Services serve internal investigators as well as external partners, in line with the provisions of the FFRDC contract. Examples of core research support activities include human cell therapy, Human Leukocyte Antigen and B-cell Lymphoma cell typing, nanomedicine pharmacokinetics, ultrasensitive detection of Simian and Human Immunodeficiency Virus, preclinical evaluation of antineoplastics for pancreatic cancer, gnotobiotics, and small animal imaging. Since FNLCR laboratories are often also involved in national mission programs and research projects described in the previous section, the matrixing of broad expertise, use of analytical technologies, and tie-in to the greater scientific community ensures that FNLCR’s core research services comprise a unique value to investigators.

III REQUIREMENTS

FFRDC Strategic Planning, Execution, and Innovation To meet the goals for the FFRDC, the Contractor must attract and retain high-quality staff in all domains [scientific research/research and development (R/R&D), business operations and facilities operations]. The evolution of R/R&D approaches, the availability of novel technologies and more sophisticated commercial services, and the unpredictable nature of emerging scientific challenges require a continuous need for innovation. To achieve innovation within the broad scope identified by the NCI and as an actively planned and executed organizational process, the contractor shall:

· In conjunction with key stakeholder input, define, implement, and utilize key performance metrics for innovation and operations

· Develop and routinely apply milestones, go/no-go decision points, and risk assessments for novel initiatives in order to execute a fast-acting response to emerging health crises

· Develop and employ processes and management principles to ensure progress in innovation In order to maintain alignment with evolving strategic objectives, the Contractor shall assess designated activities, projects for potential sunsetting when services are no longer needed due to commoditized state or when they could be performed better by non-FFRDC entities. Ultimately the NCI will determine which areas to sunset and where to redirect resources. The contractor shall develop and implement a plan for monitoring activities/projects and provide recommendations to the Government. The Contractor shall also continually perform a landscape analysis of academic and industrial R/R&D advancements and gaps, to identify and advise on future R&D opportunities and strategic partnerships. The Contractor shall identify unique niches where the FNLCR can innovate and achieve scientific contributions, which will further the strategic objectives.

Strategic Planning, Execution, and Innovation in Scientific Operation The Contractor shall:

· Regularly engage Government leadership, and program staff to ascertain needs and goals

· Routinely assess staff skill sets and FNLCR capabilities. Determine the most cost-effectiveness and reasonable way to fill expertise gaps within program funding, such as hiring, subcontracts, contractor Cooperative Research And Development Agreements (CRADA), consortia, etc.

· Boldly launch new Government approved projects and national mission programs, analyze data and outcomes, and identify niches where the FNLCR can innovate and achieve significant scientific contributions Strategic Planning, Execution, and Innovation in Business and Operations The Contractor shall:

· Regularly gain insights into best business practices at comparable institutions

· Continually review and improve upon the organization and operations. Employ streamlining, process improvements and proactive problem solving

· Ensure all aspects of business, operations and facilities support scientific endeavors in an efficient, effective, transparent and cost-effective manner

· Achieve continuous improvements in customer service support of FFRDC scientific staff and government scientists and programs

· Collaboratively, proactively and transparently engage stakeholders to meet the mission

FNLCR Technical Capabilities

The Contractor shall support NCI/Government-initiated collaborative research and research support; conduct Government-initiated, Contractor executed projects; and Contractor-initiated and executed projects as approved by the Government. Additionally, the Contractor shall provide research and research support for NIH ICs and other federal agencies. All sponsored work shall be within the mission of the FNLCR and approved by the Government.

The research and research support provided by the Contractor is frequently provided as an integration of several technical capabilities to fulfill the complex project/program requirements of the Government. Each technical capability and set of integrated capabilities shall be provided with high quality, state-of-the-art technical and scientific/medical expertise. Moreover, the Contractor shall continually evaluate and communicate to NCI any existing technology and methodology to determine if enhanced state-of-the-art technology and methodologies should be applied to achieve higher quality and/or more robust/advantageous results.

The research and research support shall encompass a wide range of scientific and technical disciplines, as described below.

Program Management The Contractor shall provide management of the prime and subcontracts, in coordination with the NCI/Government, provide management of subcontracts to ensure streamlined management, staffing and oversight of all research, research support, facility operations, business and administrative operations assigned to the FNLCR and executed on and off-site of the FNLCR. The Contractor shall have a comprehensive understanding of all activities and their interrelationships embedded in the science, and shall be responsible and accountable for the planning, execution, completion, assessment and delivery of all assigned work. The Contractor shall also be responsible for furnishing corporate leadership, including key personnel and scientific, management, analytical, technical and support personnel with the requisite experience and expertise to conduct all activities and operations needed by the Government.

To carry out the recurring and ad hoc activities outlined herein, the Contractor shall implement appropriate program and project management systems to initiate, track progress and achieve cost-effectiveness in work activities. This includes, but is not limited to, developing integrated plans and schedules to achieve program objectives; actively seeking input from stakeholders; maintaining sufficient technical expertise to accomplish the work and manage activities/projects throughout the project/program lifecycle; maintaining equipment and infrastructure; and utilizing appropriate technology and management systems to achieve cost efficiency, performance, and accommodate urgent and shifting priorities. In addition, the Contractor shall provide a proactive approach in identification/recommendation of solution(s) to issues that emerge and provide this to contractor leadership and government stakeholders.

The Contractor shall provide on a continual basis clear, accurate and concise verbal and written communication with all stakeholders as this is an integral part of biomedical research. These communications are required for both administrative and scientific activities, and may include, but are not limited to, reports (scientific, financial, etc.), periodic or ad hoc meetings, seminars, posters and publications.

Scientific Operations Advanced Scientific Computing and Bioinformatics The Contractor shall be highly knowledgeable in the recent expansions of the volume and breadth of biological data coupled with expertise in the rapid advances in computational approaches for integrating and co-analyzing disparate data types which has created unprecedented opportunities for biomedical research and development. The Contractor shall successfully meet the challenge to compile extremely large, diverse streams of data and automate both pattern identification and analytic model-building which is expected to drive the next wave of breakthroughs in both cancer and infectious disease research. These needs cut across the FNLCR National Programs and portfolios of the NCI at Frederick stakeholders, and require leveraging both existing and emerging data resources. It is therefore imperative that the Contractor shall provide expertise to continuously develop advanced and highly collaborative approaches, services, and infrastructure across five (5) broad, interconnected areas of information technology and computational science to support NCI at Frederick’s major data-driven initiatives. Overarching requirements for each of the five (5) broad areas and examples of current initiatives they enable include but are not limited to those discussed below. Note that while many of the requirements relying on advanced scientific computing and bioinformatics will be specific to individual task areas, the Contractor shall leverage the approaches developed for individual projects to address similar needs across the contract to the greatest extent possible. The Contractor also shall utilize government-provided platforms, software, and other resources where applicable.

Data Science The Contractor shall operate under the broad definition that data science occurs at the confluence of information systems, information technology, machine learning, and scientific domain expertise. In the biomedical realm, data science is typically a highly interdisciplinary team science effort aimed at discovering the cause and effect relationships underlying human disease by building on statistical correlations from bioinformatics and incorporating other disciplines such as machine learning, advanced database querying, application and user interface programming, and data systems engineering, coupled with in-depth knowledge of the biological system(s) under study. The Contractor shall provide expertise to support numerous stakeholders’ requirements for data science-based approaches to integrate and analyze large and diverse data sources, including many kinds of “omics” data (e.g. genomic, transcriptomic, proteomic, metabolomic, microbiomic), drug screening, chemistry, imaging, epidemiologic, and clinical data to identify new biomarkers and molecular targets, and to support the development of novel therapeutics. Examples of some of the current data science-driven efforts supported by the FFRDC contract include:

· The RAS initiative is a National Mission Program aimed at identifying and attacking molecular targets within the oncogenic RAS pathways, which collectively account for about 30% of all human cancers. The Initiative uses a hub and spoke model, with centralized laboratory and data science resources and project coordination hosted and coordinated at the FNLCR hub and collaborative spoke projects conducted with extramural academic researchers, biotech and pharmaceutical companies, and other government agencies. The RAS Initiative generates and aggregates a wide variety of data from structural, biophysical, imaging, molecular, and genomic studies and uses advanced bioinformatics, data mining, and machine learning-based molecular modeling approaches to elucidate potential targets and candidate inhibitors for testing and validation. https://www.cancer.gov/research/key-initiatives/ras

· The NCI Cancer Research Data Commons (CRDC) is a cloud-based data science infrastructure that connects data sets with analytics tools to allow users to share, integrate, analyze, and visualize cancer research data to drive scientific discovery. The CRDC is a virtual, scalable data ecosystem that leverages state-of-the-art data management systems and analysis platforms coupled to on-demand elastic cloud computing capacity. CRCD provides secure access to analytic tools and harmonized data across multiple scientific domains. Contractor support is required to build, administer and enhance the current CRDC nodes, including the Cancer Genomic Data Commons, Imaging Data Commons, Integrated Canine Data Commons, Cancer Data Service, Clinical Trial Data Commons, and Proteomic Data Commons; and to develop, deploy, and administer future nodes and analytic resources as they are launched. Advanced data management services and expertise are also needed for data submission, quality control, harmonization to standard data models, data aggregation and integrated querying, application software development, documentation, data security, and release and communication to the scientific community. https://datascience.cancer.gov/data-commons

The Contractor shall provide expertise and services to support these major areas of data science-intensive research which include but are not limited to:

· Developing, training and supporting artificial intelligence-based analytical approaches, including the use of machine learning, deep learning and natural language processing for such areas as:

· computational modeling (e.g., prediction of drug properties and molecular dynamics simulations – see Drug Discovery and Development section);

· image and biomolecular structure analysis (see, e.g., Imaging and Structural Biology sections);

· integrative analysis of disparate data types (e.g. combinations of multiple omics data types, including genomics, transcriptomics, proteomics, and metabolomics; quantitative biomedical imaging data derived from digital spatial profiling, brightfield and fluorescence digital pathology, and diagnostic radiology modalities, such as computed tomography (CT), magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET); quantitative chemistry data derived from drug screening and pharmacokinetic and pharmacodynamic studies; and clinical data, including structured clinical trial data as well as data mined from Electronic Health Records (EHRs).

· Migrating databases and analytical workflows to or between Cloud environments

· Using both government-provided and contractor-developed software, platforms and computational algorithms in an integrated manner to collect, harmonize, integrate, analyze, visualize and interpret high-dimensional, multivariate data

· Advising and assisting with statistical design of experiments, data mining and other knowledge discovery approaches, and workflow analysis and applications development

· Developing and deploying web-based scientific applications

· Developing and maintaining serverless Application Programing Interfaces (APIs)

· Working with the NCI’s training groups to coordinate, organize and provide data science training to NCI's scientific staff

Bioinformatics and Advanced Scientific Computing Methods The Contractor shall operate under the broad definition that bioinformatics is the application of statistical and computational analytic methods to large datasets of biomolecules, commonly biopolymer sequence data such as genomic sequence data, and gene expression data at the RNA and protein level, but also including other kinds of macromolecule and small molecule data, such as metabolite profiles. The Contractor shall incorporate additional functional information, to which expertise in bioinformatics shall provide statistical correlations for molecular variants (e.g. specific alleles, protein markers, and 16S rRNA species) in association with normal and disease states, drug responses, evolutionary distance between organisms, relative abundance of microorganisms within the microbiome and other relationships. In addition to bioinformatics, the Contractor shall use advanced computational methods, as needed, to analyze the composition of a number of different classes of biological molecules present in cells and tissues that can be measured by high throughput methods (“Omics” data). Computational approaches shall be used to characterize, model, and simulate higher order molecular structures and molecular interactions, to evaluate the bioavailability of candidate drugs, to elucidate molecular structures, and to perform quantitative image analysis. Taken together, these computational methods that shall be provided by the Contractor, form the foundation for many of the analytic workflows required by the government. Therefore, the Contractor shall provide expertise in advanced scientific computing and bioinformatics, support for development and maintenance of analysis pipelines, and training in relevant computational and bioinformatics methods necessary to support the full spectrum of research carried out by the government, including but not limited to:

· Bioinformatics services and expertise to support genomics, epigenomics, and transcriptomics studies, typically involving processing and analysis of next-generation sequencing (NGS) data including whole genome, exome, RNA, and single cell RNA sequencing, digital spatial profiling, targeted gene resequencing, pyrosequencing, chromatin immunoprecipitation assay sequencing, and other NGS data types and applications, as they come into use.

· Computational biology and application of bioinformatics methods for analysis of other kinds “omics” data, including analysis of protein, metabolite, polysaccharide, and lipid profiles, and integrated co-analysis and interpretation of proteomic, metabolomic, glycomic and lipidomic data with genomic data for multi-omics studies.

· Application of advanced computational methods for analysis of X-ray crystallography, small angle X-ray scattering, electron microscopy, cryo electron microscopy, and microcrystal electron diffraction data for protein structure determination.

· Computational support for pharmacokinetic studies to assess absorption, distribution, metabolism, and excretion (ADME) properties of therapeutic compounds and candidate drugs both in vitro and in vivo

· Computational analysis of quantitative structure-activity relationships, nanoparticle characterization, and analysis and modeling of protein-protein, protein-nucleic acid, and protein-small molecule interactions.

· Development and application of quantitative analysis and machine learning approaches for image analysis, including digital pathology, fluorescence and brightfield microscopy, and highplex applications.

· Development, deployment, and maintenance of bioinformatics tools, data analysis pipelines, and databases that leverage government-furnished and open source software, platforms, cloud resources when available and appropriate.

· Provide training and educational resources to researchers in processing, analyzing, and interpreting data with state-of-the-art analytical approaches and platforms.

Cloud Computing The Contractor shall provide expertise in cloud computing and shall operate under the broad understanding that cloud computing offers many advantages for biomedical research, due primarily to the instantaneous scalability of cloud computational capacity (autoscaling), cloud architecture (e.g. virtual private clouds) and cloud-native workflow services and orchestration technologies (e.g. Kubernetes.) In the cloud, the Contractor shall support researchers’ ability to take the compute to the data, rather than transferring and redundantly storing ever-expanding caches of data around multiple separate computing resources. Moreover, the amount of computational resources consumed shall be dynamically scaled to demand, without additional infrastructure investment; thereby eliminating the need to choose between over-provisioning computational infrastructure to meet periodic spikes in demand or accepting the latency caused by bottlenecks in computational capacity. The Contractor shall use the cloud environments to test and optimize new, experimental workflows that can be rapidly deployed without long-term hardware commitments; the importance of this capability cannot be over-emphasized. Finally, the Contractor shall provide expertise in cloud computing that offers the government access to extensible analytic platforms equipped with state-of-the-art capabilities and intuitive user interfaces where data and tooling can be easily shared, and large and disparate datasets can be rapidly integrated. The Contractor shall provide expertise in cloud computing that will fully utilize the power of cloud computing and successfully navigate its challenges, including but not limited to determining which efforts are best performed in the cloud, adapting and migrating existing workflows to the cloud, developing new cloud-native applications, transferring, storing and accessing data, and optimally leveraging cloud resources. Examples of support that shall be provided by the Contractor to the government, include but are not limited to:

· Developing, in close coordination with NCI and other NIH IT management staff, cloud computing strategies and migration plans, with special emphasis on developing hybrid solutions and leveraging Science and Technology Research Infrastructure for Discovery, Experimentation, and Sustainability (STRIDES) and other NIH or NCI cloud adoption efforts

· Advising on appropriateness of specific cloud resources and services across the cloud providers, including AWS, Google, and Azure.

· Designing, deploying, managing, operating, and monitoring cloud applications and utilizing existing NCI cloud resources and environments to the greatest extent possible.

· Supporting secure data collection from scientific instrumentation, short-term local storage, and subsequent transfer to on-premises and cloud data centers or storage sites, as appropriate

High-Performance Computing (HPC) The Contractor shall provide expertise in the support of computationally-intensive functions that do not require the flexibility or accessibility for non-technical users offered by the cloud and can be most efficiently provided with on premises computational resources. For example, steady loads of imaging or sequencing data processing can be reliably accomplished with less expense and minimal data transfer latency on computing resources proximal to the data-generating instrumentation. The NIH Biowulf and the Frederick Research Compute Environment (FRCE) HPC facilities offer extensive batch and parallel computational capacity based on modern HPC CPU and GPU nodes for such applications. The specialized FRCE environment is tailored to support FNLCR and NCI at Frederick data processing and analysis needs and includes high performance storage, SLURM batch job software, and high-speed network connectivity for Frederick-centric labs. The Contractor shall provide support for HPC including, but not limited to:

· Consulting with NCI on the development and provision of HPC resources and services to support FNLCR activities and other NCI efforts in the context of NCI’s existing and planned IT infrastructure, when they are not available at NIH. This includes the development of hybrid on-premises/cloud solutions.

· Advising users on the development of efficient workflow architectures for complex, linked data processing and analysis workflows, including the design of hybrid on premises-cloud workflows.

· Working with NCI network and infrastructure resources to develop and document requirements for engineering, installation, configuration, maintenance and support of the high-performance computing environment, with special emphasis on enhancing capabilities and reducing latency.

· Developing and implementing data analysis pipelines in consultation with scientific program staff that utilize HPC technologies (See, e.g., Structural Biology section below).

Engagement with entities within and beyond NIH The Contractor shall successfully collaborate with other computationally focused entities within NCI, NIH, and other Federal and academic institutions engaged in advanced computational and data science efforts which is essential to support and enhance data science-based government research. To this end, the Contractor shall maintain state-of-the-art expertise in the development of the most advanced computational resources which is frequently driven by physical sciences. In order to leverage resources such as exascale computing for application to cancer and other disease research it is expected that, in consultation with NCI, the contractor shall be prepared to lead and coordinate engagement activities including but not limited to:

· Leveraging unique resources available through collaboration to develop or expand computational approaches or share new insights

· Participating in working group(s) to discuss and develop assessments and recommendations on existing resources, future needs, and scientific, computational and technology trends

· Coordinating efforts to develop collaborative opportunities and novel approaches with the aim of accelerating government research and leveraging new or unique computational or data science resources

· Identifying potential opportunities for collaborations with groups inside the NIH.

· Raising visibility of government data science activities within the larger biomedical research community

Animal Sciences The Contractor shall provide comprehensive support services for NCI/NIH/HHS and other Government scientists performing animal-based research, by providing routine and specialized husbandry services on the NCI campuses (Bethesda and Frederick, or other government approved locations). The Contractor shall provide animal science support including, but not limited to, veterinarian care, regulatory and protocol support, and technical support. The Contractor shall also provide expertise and support for several state-of-the-art animal science laboratories as specified by the Government.

The animal holding facilities shall be maintained in compliance, as directed by the Government, with regulations and guidelines that include, but are not limited to, American Association for Accreditation of Laboratory Animal Care (AAALAC) accreditation, the Guide for the Care and Use of Laboratory Animals, and all Public Health Services (PHS) and Animal Welfare Act regulations. In addition, the Contractor shall provide the following capabilities, which include, but are not limited to:

· Conventional, specific-pathogen free and gnotobiotic facilities

· Daily husbandry, breeding, experimental and surgical procedures, veterinary care, animal tagging, animal health surveillance; including, but not limited to, selected amphibians, zebrafish, selected rodents, and some non-human primates

· Cage washing services, and cleaning and disinfection of facility and animal holding equipment (e.g.,racks, cages, filter tops, etc.) as necessary

· Ordering of research animals and supplies, including animal food, bedding, and caging

· Shipping of research animals

· Provide and maintain an animal inventory system

· Environmental monitoring

· Facility management and administration

Receiving and quarantine support shall include, but not be limited to:

· Receipt and quarantine of incoming animals and animal tissues

· Isolation of animals that may possess infectious hazards

· Provision of on-site facilities and technical capabilities for embryo, sperm, and/or caesarian rederivation of mouse strains, as well as for the quarantine of “rederived” rodents until their health status is confirmed

The Contractor shall operate an animal diagnostic laboratory that will ensure disease prevention, detection and eradication for all designated areas that produce or house research animals or animal cells and tissues. The serological and molecular diagnostic systems that the lab employs, shall include, but not be limited to, assays designed specifically to identify the viruses, bacteria, and parasites that infect select rodents such as mice, rats and guinea pigs, as well as other vertebrates.

The Contractor shall develop and maintain capacities including, but not be limited to:

· Specimen collection, storage and processing

· Isolating and identifying protists and parasites in specimens

· Coordinating diagnostic requests

· Diagnosing abnormal animal health conditions employing serological testing and other systems

· Interpreting diagnostic test results and reporting abnormal results

· Evaluating the health status of source colonies

· Implementing procedures for eradicating adventitious agents from cell cultures

· Developing and implementing novel diagnostic procedures

The Contractor shall provide diagnostic procedures including, but not limited to, serological and molecular testing, genetic monitoring, and verification of defined flora in experimental animals. Assurance shall be provided of pathogen status, defined flora status and genetic integrity. The Contractor shall also provide high-throughput animal genotyping and speed congenics to identify mouse strains and guide mouse breeding strategies.

The Contractor shall implement a modern software system to facilitate the tracking and maintenance of animal inventory, breeding, weekly accounting of occupied cages linked to user/protocol/cage type information, technical hours and health status.

The Contractor shall employ veterinarian(s) with VMD/DVM degree(s), who shall provide clinical veterinary care, preventative medicine, training of personnel in the humane care and use of laboratory animals, as well as have primary responsibility for maintaining AAALAC accreditation and assuring compliance with The Guide, all PHS and Animal Welfare Act regulations, and other accreditations and compliances as designated by the Government.

All procedures shall be conducted in a humane manner in a controlled environment, and all animal housing and procedures shall conform to the most recent version of The Guide for the Care and Use of Laboratory Animals. All animal work shall be done in collaboration with the Animal Care and Use Committee (ACUC), which is responsible for the development, implementation, and oversight of animal programs, procedures, and facilities in compliance with the PHS Policy on the care and use of laboratory animals, the Animal Welfare Act regulations, and The Guide, as well as maintaining accreditation by AAALAC International.

The Contractor shall be responsible for providing administrative support to the NCI-Frederick ACUC and the NCI-Bethesda ACUC, and assist principal investigators in preparing their Animal Study Proposals (ASPs).

The Contractor shall operate, manage, and provide scientific and technical expertise for in vivo preclinical drug efficacy, vaccine efficacy, pharmacokinetic, pharmacodynamic and toxicology studies, including, but not limited to:

· Generating genetically engineered (transgenic and gene targeted) rodent tumor models

· Establishment of primary tumor cell culture

· Establishment of primary tumor cell lines from genetically engineered mouse (GEM), GEM-derived allograft (GDA), or patient derived xenograft (PDX) models

· Surgical techniques for generation of murine orthotopic transplant model cohorts

· Implanting tumor xenografts (including PDX) in mice

· Administering experimental drugs to animals, including targeted and immune-based drugs

· Administering experimental vaccine candidates and challenging animals using ABSL2 pathogens

· Developing protein- and nucleic acid-based assays to identify molecular pathways involved in tumor regulation and to evaluate in vivo responses to experimental drug treatments

· Assessing outcomes of drug treatments via histology, pathology, and small animal imaging, including, but not limited to, magnetic resonance (MR), computed tomography (CT), single photon emission computed tomography (SPECT), ultrasound, and positron emission tomography (PET) imaging modalities

· Cryopreservation of animal models and specimens, including rodent embryos, sperm or ovaries; and recovery of animal models from cryopreserved material

· Capabilities for (i) germ-free animal experimentation, (ii) developing and maintaining an axenic (germ-free) breeding colony, (iii) using ABSL2 pathogens in studies within the facility, (iv) testing different methods of rederiving multiple strains to germ-free status, and (v) supporting studies involving “wildling” mouse models with natural microbiota at specific body sites

· Genomics modification utilizing nuclease methodologies (including CRISPR) to generate somatic and germ-line mutations in cells and in whole organisms

The Contractor shall also support a technology development operation, which shall provide, but not be limited to:

· Enhancement of existing shared service capabilities

· Innovation of capabilities that could become new shared service, scientific publication and/or patentable invention

· An additional training fellowship for technology innovation

The Contractor shall be fully responsive to changing animal needs of the Government.

Assay Development and Execution The Contractor shall develop and perform assays to support basic, preclinical and clinical research at the NCI and collaborating Governmental and extramural institutions.