Attachment_4,_Basic_IDIQ_SOO.pdf

STATEMENT OF OBJECTIVES

(BASIC IDIQ)

Molecular Assessment Sensing Technologies (MAST) Program

1.0 BACKGROUND

This effort is soliciting innovative research concepts that advances the overall mission of the Applied Biotechnology Branch, which is to provide advanced scientific knowledge and performing technology development to determine Airman state through biological, physiological, and molecular sensing in real-time to enhance the warfighter performance and enable Airman-machine operations. The 711th HPW Airman Systems Directorate in AFRL provides the Air Force research in human-centered research vision, integrated biological, and cognitive technologies to optimize and protect the airman’s capabilities to fly, fight, and win in air, space, and cyberspace. The National Defense Strategy (NDS) calls out a need to develop new technologies, including advanced computing, “big data” analytics, directed energy, and biotechnology—the very technologies that ensure we will be able to fight and win the wars of the future. Also called out in the NDS is a concern that recent advances in bioengineering increase the potential, variety, and ease of access to biological weapons.

2.0 SCOPE

The Contractor will provide basic, applied, and advanced technology development research as well as development and demonstration for discovering and sensing molecular signatures of Airman performance and the operational environment. This research may include both laboratory and field research. The Contractor will perform research conducting field research at government facilities; and/or industrial settings; and/or conduct research at university settings. The warfighter domains of application for this research may include but are not limited to high altitude aircraft cabins, dismounted operational settings, ISR analyst cells, and Air Force flightlines. The research proposed herein must align to ALL of the following technical areas: (1) Molecular Tools for Biosignature Tracking; (2) Engineered Mircoorganism-based Sensing; (3) Exploiting Host-Microbe Interactions; (4) Real-Time Molecular Sensors and Testing; (5) Biomarker Discovery; (6) Air Quality Monitoring; (7) Data Sciences; (8) Catalytic Single Domain Antibodies; (9) Biological Recognition Elements for Extreme Environments; (10) Development of New Synthetic Biology Tools; (11) Development of 3d In vitro and In Silico Mechanistic Models for Human Performance Assessments; (12) Omics Technologies and Bioinformatics; and (13) Toxicity Assessments.

3.0 TASKS/TECHNICAL REQUIREMENTS/OBJECTIVES

The work under this effort will be implemented through an indefinite delivery, indefinite quantity (IDIQ) contract-by specific task orders.

3.1 TECHNICAL AREAS/OBJECTIVES

3.1.1 Molecular Tools for Biosignature Tracking

This technical area advances the science and technology associated with understanding, developing and applying engineered biosensors for assessment and augmentation of human performance as well as the impact of chemical and/or genetic exposures to human health and performance. This technical area may include, but is not limited to: 1) developing high throughput methods for screening biorecognition elements (including peptides, DNA and RNA aptamers, enzymes, transcription factors, etc.) for human performance related biomarkers, 2) developing, implementing, and fielding engineered microorganism-based sensors to modify bacteria to sense and respond to Air Force related targets of interests, including chem/bio agents for surveillance and biomarkers for diagnostic applications, 3) developing and demonstrating the use of real-time biosignature tracking sensors for biomarker detection in biofluids to use in point-of-care diagnostics, 4) developing and exploring molecular tools that expand current capabilities to monitor neurochemicals in the brain and peripheral tissue to aid understanding of brain function, and 5) develop nanomaterial-based sensing platforms for rapid and sensitive quantification of biomarkers and different analytes in the field, as well as the study of the fundamental interactions governing the sensing properties of bio-nano hybrids.

3.1.2 Engineered Microorganism-based Sensing

This technical area develops and optimizes tools for selection and in silico design of elements to control gene expression in a variety of microorganisms and their cell-free transcription/translation systems in response to a target of interest. This effort utilizes high through-put methods to increase speed of selection of new switches and binding characterization to support a pipeline for in silico design novel sense and respond mechanisms.

This work involves, but is not limited to, the integration of multiple cell lines that sense different targets and communicate with each other to assess a complete scenario and provide decision-making capabilities to be integrated in fieldable complex sensors for autonomous surveillance. Expanding this work to improve the Airman health, this effort also focuses on characterizing components of the human microbiome in different tissue/organs and generating engineered human microbiome components for disease prevention/treatment. This area will also include investigation into discovery of new transcriptional/translation control mechanisms in culturable organisms and extremophiles, which will provide new synthetic biological tools for specific mission-centric applications.

3.1.3 Exploiting Host-Microbe Interactions

This technical area focuses on characterizing how components of the human microbiome in different tissue/organs are affected by conditions experienced by the warfighter during their deployment. These deployed conditions can be real or simulated using in vitro, in vivo, or in situ models. Discovery and analysis of signatures of performance degradation and/or disease, as well as signatures of performance optimization. Efforts in this area also include Host- Microbiome signal discovery – the identification and characterization of molecular microbe and/or host output for modulator effects in target tissues such as the brain, muscle, liver, etc.

Discoveries will lead to interventions pertaining to human performance optimization and disease prevention/treatment. These may include prebiotic, probiotic, synbiotic strategies, as well as engineered human microbiome components that sense and respond to changes in human performance and disease.

3.1.4 Real-Time Molecular Sensor Development and Testing

This technical area covers exploratory sensor development on biomarker sampling and analysis that provides targets including, but not limited to, exhaled breath, saliva, odor, and perspiration, to sense and assess a variety of individual physiological and health levels. In addition to developing, implementing, integrating, and automating analysis tools to advance the utility of Human Performance through Physiological Assessment, this effort will produce algorithms to enable staff to better predict performance and enhance recovery from physiological exertion. Experiments may include, but not be limited to: 1) investigating the key factors in high performance chemical and biochemical molecular sensor development, 2) enhancing the sensing performance to target molecules on nano/bio materials and electrode arrays by probing their chemical, biochemical, optical and electronic signatures, 3) transforming molecular affinity and sensing technology towards array-based sensing elements, 4) generating target-specific diagrams/charts, and 5) expediting sensing platform development by constructing a rapid-real time molecular sensor development pipeline, 6) development of new robust biological recognition elements, 7) the development of sensor systems that include both wearable and point-of-use diagnostics for physiological and performance monitoring which leverage handheld, smartphone technologies, 8) correlating physiological sensor data to performance and incorporate into a single database, 9) producing state-of-the-art bioinformatics platforms and software systems that can intelligently analyze the sensor signature data and incorporate autonomous notification and threat analysis for detected signatures, 10) developing recommended recovery techniques based off of sensor data that will enhance performance, 11) validating commercial off the shelf technologies and molecular sensors developed for biological, chemical and/or environmental material analysis, and 12) performing collection, monitoring and analysis of signatures potentially relevant in correction of operational deficiencies.

3.1.5 Biomarker Discovery

This technical area focuses on 1) identifying markers and mechanisms of human performance for conditions such as stress, fatigue, hypoxia to recognize and take appropriate measures to counteract the effects prior to performance degradation, 2) using non-invasive or minimally-invasive media to collect exhaled breath and bodily fluids such as saliva, blood, urine, and sweat to minimize the impact of Air Force operators in various working conditions, 3) developing and testing tools to enable collection, sensing, and proper processing of biomarker,

4) Identifying and validating biological, physiological and/or molecular markers detectable using non-invasive methods that are indicative of performance traits and state changes, intentions and committed actions, 5) selecting sensitive and specific markers suitable for human-machine bidirectional information flow and communications, and 6) incorporate selected markers into novel human-machine interaction paradigm(s) for warfighter training and performance augmentation.

3.1.6 Air Quality Monitoring

This technical area covers aircraft air quality, as well as general environmental and occupational sampling to enable personnel to perform risk assessment. This Techical Area may include testing commercial-off-the-shelf sensor technologies, developing sensors specific to the desired operational environment, and determining changes to technologies to enable mission readiness using statistical analysis, machine learning techniques and differential profiling tools.

3.1.7 Data Science

This technical area involves, but is not limited to, the analysis of diverse datasets to forecast behavior, interpret multimodal time series, explore variance, discover knowledge within high dimensional data, with the intent to better understand sensor system design, development, interpretation and analyte identification with application to human performance monitoring.

Research may be conducted to lower bias or variance when analyzing biological datasets, to develop novel analytical techniques to automate efficient processing of terabytes of sequence data, and to engineer data features from complex system sensor measurements to correlate with various biochemical, physiological or aeromedical endpoints. Key elements of the research will involve programming, scalable parallel implementation of analytics, multivariate statistics, time series analysis, Bayesian methods and empirically demonstrating the benefits of proposed data methods.

3.1.8 Catalytic Single Domain Antibodies

This technical area will focus on development single domain antibodies (CSDA) with functional properties heretofore not found in nature. Domain-fused proteins will be used to develop new enzymatic reactions or recognition sites that can be exploited for targeted microbiome properties using engineered commensal bacteria or theranostics. Areas include but are not limited to: 1) sensitive sense/report molecules for low concentration molecules in biological/environmental samples; 2) brain-targeting CSDAs; 3) engineered target-specific artificial cell-surface receptors.

3.1.9 Biological Recognition Elements for Extreme Environments This technical area will focus on the development of small synthetic proteins, peptides, or single domain antibodies for use as analytes capture elements which maintain field or in situ stability and sensitivity in harsh environments such as fuel tanks, or human environments such as high humidity, heat, cold, low oxygen.

3.1.10 Development of New Synthetic Biology Tools

This technical area will focus on development of new molecular tools and methodologies for engineering bacterial, fungal, viral, or eukaryotic chassis systems for precise modulation or enhancement of human performance or protection. Developed tools may also be utilized to develop new sensor or sense/respond techniques.

3.1.11 Development of 3D In vitro and In silico Mechanistic Models for Human Performance Assessments

This technical area will focus on research to develop 3D in vitro models by using multiple interconnected cell lines to mimic the structure and function of a native tissue and study the mechanistic and physiological effects of diverse stressors to obtain predictive data to assess human performance. Overall, this technical area focuses on: (1) development of physiologically relevant in vitro test beds; (2) integration of engineering and cell biology to produce dynamic tissue surrogates; (3) creation of microfluidic-based organ-on-chip technologies; (4) interrogation of molecular mechanisms from the laboratory test beds; (5) screening of countermeasures to operation stress; (6) integration of real-time monitoring technologies providing increase bandwidth both temporally and spatially; (7) incorporation of diverse in vitro and in vivo data into dynamic mathematical systems that purport to represent causality, covering the spectrum from cell biology [Systems Biology Markup Language (SBML) and agent based modeling (ABMs) to human physiology (pharmacokinetic/pharmacodynamics (PBPK/PD) models]. Time derivatives representing changes in biological variables and processes (binding, transport, biochemistry, synthesis and degradation) are written as functions of those same biological variables, so that causal and feedback loops are included. This allow for prediction and extrapolation of endpoints across doses and routes, species and time. Finally, the program is aimed to evaluate Airman stressors, produce a molecular mechanistic road-map, and direct intervention strategies to enable, sustain, or enhance performance.

3.1.12 Omics Technologies and Bioinformatics

This technical area will focus on using 1) Genomics technology including microchip gene array to investigate global gene expression profile to identify novel targets indicators of human performance, 2) Proteomics, for the identification and quantification of overall proteins present in an organisms as well as studying the regulatory systems that control their expression, 3) Metabolomics to investigate the interactions of diverse metabolites and their correlation with diverse phenotypes linked to human performance, 4) Bioinformatics, use of novel systems and computational methods for the understanding of large and complex biological data to identified pathways and develop models to advance the scientific knowledge on living systems, 5) using a range of next generation sequencing techniques which may include, but not limited to 16s/18S metagenomics, shotgun metagenomics, RNA-seq that will be used to address changes in the gut microbiome and the use of transcriptomics to evaluate gene expression biomarkers. Data analysis will be used to correlate changes in the microbiome and relate it to how the microbiome influence (gut-brain axis) the expression of blood-based/saliva based biomarkers.

3.1.13 Toxicity Assessments

This technical area will focus on high performance aircraft and sustainment exposures by 1) Offering a combination of tools and experience that can be applied to minimize operational performance degradation and prevent health risks to hazardous materials, chemicals and their mixtures; 2) Integrate Air Force chemical toxicity data with exposure assessment data as part of the chemical risk assessment process; 3) Determine the mechanisms of toxicity for military-relevant chemicals and assists in understanding the relationship between chemical structure and health effects; 4) Conduct basic and applied research in toxicity evaluation methods using animal models, cell culture, molecular biology and mathematical modeling; 5) Provide subject matter expertise to help program managers choose the least toxic chemical for a given application early in the development process.

3.2 Specific Technical Requirements (as determined by task order)

3.2.1 Data Collections

The contractor will conduct data collection activities, as necessary and determined by Air Force and user requirements. This will include as necessary developing research plans, experimental plans, human use protocols, animal use protocols and flight test plans for all data collections.

Preparation for data collection will require as necessary pilot studies and setup of a panel of readily available subjects. The contractor will collect pre-experimental pilot data to assure that the facilities are functioning within tolerances required for specific data collections.

3.2.2 Data Analysis

The contractor will conduct appropriate descriptive and inferential statistical analyses using experimental data. The contractor will represent statistical analyses using graphical, pictorial, and tabular summaries.

3.2.3 Laboratory Research

This research will require the contractor to perform at various levels within the research domain, to include research assistants and subject matter experts, to name a few. The contractor will collaborate with government researchers to create and execute experimental designs, IRB preparations, data collections, data analyses, and technical writing for RHXB research. The contractor may provide hardware or software creation or acquisition as the research deems necessary.

3.2.4 Software Development

The contractor will develop software (in the form of design prototypes, conceptual demonstrations, models, simulations, and or research platforms), as necessary, to accomplish specific research. This will include, but not be limited to, software design, software development, source code documentation, and software user’s manuals.

3.2.5 Field Research

The contractor will perform field research including cognitive tasks analysis, interviews, and survey research in the domain of molecular signatures. Field research may occur at Air Force bases, or other government or industry locations.

3.2.6 Modeling and Simulation

The contractor will perform modeling and simulation to support understanding of subsystem and system technologies and guide technical efforts. Multiscale mechanistic modeling to integrate various data, utilizing tools such as models, agent based models, neuronal networks, or systems biology markup language.

3.2.7 Developmental Research

The contractor will develop warfighter interface hardware and software (in the form of prototypes, conceptual demonstrations, models, and simulations) as necessary to accomplish specific research.

3.2.8 Flight-worthy Equipment

As required the contractor will develop, fabricate, and integrate hardware and software as necessary to test concepts in operational environments. The new equipment must be able to work in a military aircraft environment. The contractor will provide documentation on any developed or upgraded hardware or software.

3.2.9 Management of Effort

The contractor will manage technical, schedule and cost satisfaction of the task order; plan, prepare, conduct, and document reviews; track CDRL satisfaction; and interface with the customer to assess performance satisfaction and re-plan the project as needed. Contractor shall comply with all applicable human use and animal use regulations.

3.2.10 Contract Holidays Clause Will Apply To This Effort As Follows

The prices/costs in Section B of the contract include holiday observances; accordingly, the Government will not be billed for such holidays, except when services are required by the Government and are actually performed on a holiday. The following days are contract holidays:

Federally Observed Holidays as set forth herein: New Year’s Day, Martin Luther King Jr. Day, Presidents Day, Memorial Day,4th of July, Labor Day, Columbus Day, Veterans Day, Thanksgiving Day, and Christmas Day.

4.0 Security Requirements

This effort does not anticipate to exceed unclassified work.

4.1 Position of Trust

All contractor personnel require a minimum of a National Agency Check with written Inquires (NACI)/SF85 for any position that requires access to the internet, use of automated systems or unescorted entry into restricted or controlled areas prior to reporting for duty in performance of any task order. The investigation is not for a security clearance; it is for a position of trust.

This is a mandatory requirement set forth in DoD5200.1-R and AFI 31-50 l Information Security.

All documentation required for security certification shall be the responsibility of the contractor. No foreign nationals shall be employed for any task order issued under this contract without prior approval of the Government.

4.2 Operations Security (OPSEC)

The contractor shall provide OPSEC protection for all sensitive/critical information as defined by AFI 10-701 (Operations Security), the 711 HPW OPSEC Plan, and critical information list. The contractor shall participate in the 711 HPW sustained OPSEC awareness training or include OPSEC training as part of their on-going security program. The 711 HPW OPSEC coordinator shall evaluate the OPSEC posture of AF contract activities and operations.

4.3 Information Security and Force Protection

The contractor shall provide Information Security and Force Protection training as defined by AFI31 -401 (Information Security Program Management) and AFll0-245 (Air Force Antiterrorism Standards). The contractor shall participate in the 711 HPW sustained information Security and Force Protection/Antiterrorism training or include this training as part of their on-going security program. The 711HPW Security Managers shall evaluate the training posture of AF contract activities and operations. This requirement is set forth in AFI 3 1-40, AFI 10-245 and applicable AFMC and local supplements.

4.4 Individual Security Clearances

Onsite contractor personnel must have an active clearance prior to reporting for duty in performance of any task order issued. Interim clearances for newly hired personnel shall be processed as expeditiously as possible. Such clearance must be obtained through the Defense Investigative Services. The contractor shall be required to wear contractor identification badges and maintain currency in all Privacy Act Laws.