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CALIFORNIA INSTITUTE OF TECHNOLOGY
PASADENA, CA, 91125
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Other Than Small Business
Prime contracting experience
10 records from government sources. Past participation is not evidence of current teaming interest.
| Role | Agency | Description | Vehicle | Obligated | Action date | Period |
|---|---|---|---|---|---|---|
| Prime | National Aeronautics and Space Administration National Aeronautics and Space Administration | SPHEREX MISSION IS AN ALL-SKY NEAR-INFRARED SPECTRAL SURVEY SATELLITE. | — | $108,158,922 | Sep 16, 2026 | Mar 2, 2018 – May 31, 2028 |
| Prime | National Aeronautics and Space Administration National Aeronautics and Space Administration | THE ULTRAVIOLET EXPLORER (UVEX) | — | $106,965,269 | Aug 26, 2026 | Mar 21, 2023 – Feb 7, 2027 |
| Prime | National Aeronautics and Space Administration National Aeronautics and Space Administration | THIS CONTRACT IS FOR THE SERVICES REQUIRED TO SUPPORT THE ROMAN SPACE TELESCOPE SCIENCE SUPPORT CENTER | — | $53,296,381 | Aug 19, 2026 | Oct 1, 2021 – Sep 30, 2027 |
| Prime | National Aeronautics and Space Administration National Aeronautics and Space Administration | THE GOAL OF THE NEAR-EARTH OBJECT SURVEILLANCE MISSION (NEOSM) IS TO FIND, TRACK, AND CHARACTERIZE THE ASTEROIDS AND COMETS THAT COULD POTENTIALLY THREATEN THE EARTH. | — | $42,625,123 | Aug 11, 2026 | Jul 1, 2020 – May 31, 2028 |
| Prime | National Aeronautics and Space Administration National Aeronautics and Space Administration | SMALL, INNOVATIVE, MISSIONS FOR PLANETARY EXPLORATION (SIMPLEX) | — | $51,646,380 | Jul 23, 2026 | Sep 5, 2019 – Sep 30, 2025 |
| Prime | Department of Defense Department of the Navy | DARPA LINC PROGRAM | — | $13,281,871 | Jul 16, 2026 | Nov 21, 2022 – Oct 30, 2026 |
| Prime | National Aeronautics and Space Administration National Aeronautics and Space Administration | NUSTAR IS A PRICIPAL INVESTIGATOR (PI)-LED SMALL EXPLORER (SMEX) MISSION THAT PERFORMS SURVEYS AND POINTED OBSERVATIONS. THIS ACQUISITION IS IN RESPONSE TO HQ AO NNG07ZDA003O AND EXTENDS THE BRIDGE PHASE B EFFORT FROM MARCH 1, 2008 TO JUNE 30, 2008. DURING THIS PERIOD, THE CONTRACTOR SHALL: 1. MANAGE THE PROPOSED NUSTAR TASKS, PROVIDE COST AND SCHEDULE INFORMATION TO NASA AS REQUIRED; 2. WORK WITH JPL TO DEVELOP THE NUSTAR PROJECT REQUIREMENTS TO BE READY FOR SYSTEM REQUIREMENTS REVIEW (SSR). 3. DESIGN THE FOCAL PLANE ASSEMBLY, PERFORM REQUIRED ANALYSES, IDENTIFY ALL LONG LEAD PARTS, AND INITIATE LONG LEAD PROCUREMENTS AS REQUIRED. 4. DESIGN THE INSTRUMENT ENCLOSURES, SHIELD, AND APERTURE, PERFORM REQUIRED ANALYSES, IDENTIFY ALL LONG LEAD ITEMS, AND INITIATE LONG LEAD PROCUREMENTS AS REQUIRED. 5. COMPLETE THE GLASS PRODUCTION FACILITY, PRODUCE THE NUSTAR GLASSES TO VERIFY THE PRODUCTION CAPABILITY. 6. DEVELOP PROTOTYPES FOR THE OPTICS ASSEMBLY, DESIGN THE OPTICS ASSEMBLY AND THE PRODUCTION FACILITY, AND PERFORM REQUIRED ANALYSIS. 7. COMPLETE THE PRELIMINARY DESIGN OF THE MAST, CANISTER AND INSTRUMENT STRUCTURE, IDENTIFY LONG LEAD PROCUREMENTS. 8. COMPLETE THE SPACECRAFT REQUIREMENTS, PERFORM SYSTEM ENGINEERING ANALYSES, AND CONTINUE THE BASELINE SPACECRAFT DESIGN. 9. COMPLETE THE MOS (MISSION OPERATIONS SYSTEM) REQUIREMENTS AND THE PRELIMINARY MOS PLAN. | — | $139,386,816 | May 29, 2026 | Feb 29, 2008 – May 31, 2028 |
| Prime | Department of Defense Defense Advanced Research Projects Agency | EO14042. NOVEL ORBITAL AND MOON MANUFACTURING, MATERIALS, AND MASS-EFFICIENT DESIGN (NOM4D) PROGRAM. | — | $5,026,632 | Mar 12, 2026 | Dec 10, 2021 – Sep 30, 2026 |
| Prime | National Aeronautics and Space Administration National Aeronautics and Space Administration | THE EARTH SYSTEM EXPLORERS PROGRAM (ESEP) THE CARBON INVESTIGATION (CARBON-I) MISSION PHASE A CONCEPT STUDY. | — | $1,529,000 | Dec 18, 2025 | Sep 6, 2024 – Mar 31, 2026 |
| Prime | National Aeronautics and Space Administration National Aeronautics and Space Administration | WFIRST SCIENCE SUPPORT CENTER | — | $5,947,740 | Feb 2, 2022 | Dec 1, 2019 – Sep 30, 2021 |
Contract vehicles are shown only when present in the source record. Linked award numbers and vehicles open the authoritative record on USAspending.gov.
Subcontracting experience
19 records from government sources. Past participation is not evidence of current teaming interest.
| Role | Agency | Description | Vehicle | Obligated | Action date | Period |
|---|---|---|---|---|---|---|
| Subcontractor | Department of Energy | RESEARCH & DEVELOPMENT 471846 Parent award context Parent award agency: Department of Energy · Department of Energy Parent award NAICS: 541712 Parent award performance state: NY Parent award description: IGF::OT::IGF TAS::89 0222::TAS M&O CONTRACT FOR BNL View parent award on USAspending | — | $142,400 | Sep 30, 2026 | — – — |
| Subcontractor | Department of Energy | CALIFORNIA INSTITUTE OF TECHNOLOGY-STAND ALONE-ITEM LEVEL-R AND D CW127817 Parent award context Parent award agency: Department of Energy · Department of Energy Parent award NAICS: 561210 Parent award performance state: NM Parent award description: IGF::CL::IGF COMPETITION FOR MANAGEMENT AND OPERATION OF LOS ALAMOS NATIONAL LABORATORY View parent award on USAspending | — | $545,000 | Mar 12, 2026 | — – — |
| Subcontractor | National Aeronautics and Space Administration | INTERSTELLAR MAPPING AND ACCELERATION PROBE (IMAP) SUB0000928 Parent award context Parent award agency: National Aeronautics and Space Administration · National Aeronautics and Space Administration Parent award NAICS: 541715 Parent award performance state: NJ Parent award description: INTERSTELLAR MAPPING AND ACCELERATION PROBE (IMAP) IS A WATERSHED MISSION THAT SIMULTANEOUSLY INVESTIGATES THE ACCELERATION OF ENERGETIC PARTICLES AND INTERACTION OF THE SOLAR WIND WITH THE LOCAL INTERSTELLAR MEDIUM. IMAP WILL 1) ADVANCE THE UNDERSTANDING OF THE TEMPORAL AND SPATIAL EVOLUTION OF THE BOUNDARY REGION IN WHICH THE SOLAR WIND AND INTERSTELLAR MEDIUM INTERACT, 2) IDENTIFY AND ADVANCE THE UNDERSTANDING OF PROCESSES RELATED TO THE INTERACTIONS OF THE MAGNETIC FIELD OF THE SUN AND THE LOCAL INTERSTELLAR MEDIUM, 3) IMPROVE THE UNDERSTANDING OF THE COMPOSITION AND PROPERTIES OF THE LOCAL INTERSTELLAR MEDIUM, AND 4) IDENTIFY AND ADVANCE THE UNDERSTANDING OF PARTICLE INJECTION AND ACCELERATION PROCESSES NEAR THE SUN, IN THE HELIOSPHERE AND HELIOSHEATH. IMAP IS BASED ON A COMPLETE AND SYNERGISTIC SET OF OBSERVATIONS. IN SITU AT 1AU, THIS REQUIRES DETAILED OBSERVATIONS OF THE SOLAR WIND ELECTRONS AND IONS SUPRATHERMAL, PICKUP, AND ENERGETIC ION POPULATIONS AND MAGNETIC FIELD. FOR THE OUTER HELIOSPHERE INTERACTION, IT REQUIRES ADVANCED GLOBAL OBSERVATIONS OF THE REMOTE PLASMA AND ENERGETIC IONS OVER A BROAD ENERGY RANGE VIA ENERGETIC NEUTRAL ATOM (ENA) IMAGING, AS WELL AS PRECISE OBSERVATION OF THE NEUTRAL INTERSTELLAR ATOMS PENETRATING THE HELIOSPHERE. COMPLEMENTARY OBSERVATIONS OF INTERSTELLAR DUST AND THE UV GLOW OF INTERSTELLAR NEUTRALS, WHILE NOT REQUIRED FOR THE THRESHOLD MISSION, ADD IMPORTANT CONTEXT AND INSIGHTS TO DEEPEN PHYSICAL UNDERSTANDING OF THE BASELINE MISSION. THESE OBSERVATIONAL NEEDS WILL REQUIRE AN INTEGRATED AND COORDINATED SUITE OF 10 INSTRUMENTS THAT SPAN BOTH THE IN SITU AND REMOTE IMAGING ASPECTS OF THE INVESTIGATION. AS THE PI INSTITUTION PRINCETON UNIVERSITY OVERSEES THE DEVELOPMENT OF IMAP TO ENSURE COST, RISK, AND SCIENCE OBJECTIVES ARE MET IN THE CONTEXT OF AN OVERALL PLAN TO DEVELOP, INTEGRATE, TEST, LAUNCH, COMMISSION, AND OPERATE THE IMAP MISSION. PRINCETON WILL DEVELOP THE SOLAR WIND AND PICKUP ION (SWAPI) INSTRUMENT, MANAGE THE MISSION SCIENCE TEAM, DEVELOP THE INTERSTELLAR DUST EXPERIMENT (IDEX) INSTRUMENT DATA PIPELINE, INITIATE THE FUTURE LEADERS PROGRAM, AND OVERSEE THE MISSION STUDENT COLLABORATION. View parent award on USAspending | — | $93,245 | Mar 10, 2026 | — – — |
| Subcontractor | National Aeronautics and Space Administration | CHRISTINA M.S. COHEN WILL ANALYZE SIS DATA IN CONJUNCTION WITH OTHER EPD SENSORS AND SOLAR ORBITER INSTRUMENTS, PARTICIPATE IN SOLAR ORBITER WORKSHOP ACTIVITIES, PARTICIPATE IN SCIENTIFIC CONFERENCES FOR PRESENTATION OF SIS RESULTS, AND PUBLISH SCIENTIFIC FINDINGS AND DISCOVERIES IN REFEREED JOURNALS. T99347AAM Parent award context Parent award agency: National Aeronautics and Space Administration · National Aeronautics and Space Administration Parent award NAICS: 334516 Parent award performance state: TX Parent award description: SUPRATHERMAL ION SPECTROGRAPH PHASE E INSTRUMENT FOR SOLAR ORBITER MISSION View parent award on USAspending | — | $95,000 | Mar 5, 2026 | — – — |
| Subcontractor | National Aeronautics and Space Administration | WORK WITH THE TEAM TO IDENTIFY WHICH ENERGETIC PARTICLE MEASUREMENTS, FROM WHICH SPACECRAFT AND WHICH REPOSITORIES, WILL BE NEEDED/USEFUL FOR THE ANALYSIS AND INTERPRETATION OF SUNRISE DATA
• COMMUNICATING TO THE TEAM ANY NEW DEVELOPMENTS IN SEP OBSERVATIONS AND THEORY RELEVANT TO SUNRISE
• PARTICIPATE IN PLANNING FOR EARLY RESULTS PAPERS SUBK00023190 Parent award context Parent award agency: National Aeronautics and Space Administration · National Aeronautics and Space Administration Parent award NAICS: 541713 Parent award performance state: MI Parent award description: THE SUN RADIO INTERFEROMETER SPACE EXPERIMENT (SUNRISE) IS PROPOSED BY UNIVERSITY OF MICHIGAN (UM) IN RESPONSE TO NASA'S 2016 HELIOPHYSICS SMALL EXPLORER (SMEX) ANNOUNCEMENT OF OPPORTUNITY. THIS STATEMENT OF WORK (SOW) DESCRIBES THE WORK TO BE CONDUCTED BY UM DURING THE PHASE A (SUNRISE) PROJECT. UM SHALL PROVIDE THE NECESSARY PERSONNEL, MATERIALS, EQUIPMENT, AND FACILITIES TO PRODUCE THE SUNRISE PHASE A CONCEPT STUDY REPORT (CSR) THAT ENCOMPASSES: 1. PRINCIPAL INVESTIGATOR PROGRAM OFFICE. 2. INSTRUMENT SYSTEM ENGINEERING, INCLUDING INSTRUMENT MISSION ASSURANCE. 3. DESIGN OF A FLIGHT QUALIFIED SUNRISE INSTRUMENT MEETING MISSION AND SCIENCE REQUIREMENTS. 4. DEVELOP PLANS IN SUPPORT OF INTEGRATION AND TEST OF THE SUNRISE INSTRUMENT FLIGHT SYSTEM. 5. DEVELOP PLANS IN SUPPORT OF ESSENTIAL FIELD OPERATIONS 6. DEVELOP PLANS IN SUPPORT OF LAUNCH OPERATIONS, FLIGHT OPERATIONS. 7. DEVELOP PLANS FOR AND LEAD THE SUNRISE SCIENCE INVESTIGATION, AS WELL AS THE GENERATION OF RESULTING DATA PRODUCTS. UM SHALL PROVIDE A BRIEFING ON THE SUNRISE SCIENCE AND SCIENCE IMPLEMENTATION PLAN AT THE PHASE A SITE VISIT. UM SHALL PROVIDE AN ORGANIZATION CHART DEFINING UM ROLES AND RESPONSIBILITIES, REPORTING PROCEDURES, AND LINES OF AUTHORITY. PARTICIPATE IN DEFINING THE RELATIONSHIPS BETWEEN THE UM PI PROGRAM OFFICE AND THE NASA EXPLORERS PROGRAM OFFICE.. UM SHALL DEVELOP A SUNRISE INSTRUMENT SYSTEMS REQUIREMENTS DOCUMENT AND A SUNRISE MISSION SYSTEMS REQUIREMENTS DOCUMENT. UM SHALL DEVELOP DETAILED BLOCK DIAGRAMS AND TECHNICAL DESCRIPTIONS OF ALL INSTRUMENT SYSTEMS. UM SHALL CONDUCT IN-DEPTH INSTRUMENT-LEVEL REVIEWS OF THE PROPOSED INSTRUMENT DESIGN. CONDUCT ESSENTIAL TRADE STUDIES, ANALYSES, MODELING AND SIMULATIONS TO ASSURE COMPLIANCE WITH INSTRUMENT REQUIREMENTS. UM SHALL LEAD THE SCIENCE TEAM. UM SHALL DEVELOP AN INSTRUMENT-LEVEL TEST PLAN AND PARTICIPATE IN PLANNING FOR INTEGRATION AND TEST. UM SHALL PREPARE A DETAILED INSTRUMENT DEVELOPMENT SCHEDULE COVERING ALL MISSION PHASES, LISTING MAJOR MILESTONES AND INCLUDING A DEFINED CRITICAL PATH AND SCHEDULE RESERVES. View parent award on USAspending | — | $78,000 | Jul 29, 2025 | — – — |
| Subcontractor | Department of Defense | 1. YEAR 1: - OPTIMIZE DOUBLE METASURFACE LAYERS FOR COUPLING BETWEEN NITRIDE AND OXIDE
WAVEGUIDES AT NEAR INFRARED WAVELENGTHS
2. YEAR 2 - OPTIMIZE DOUBLE METASURFACE LAYERS FOR COUPLING BETWEEN NITRIDE AND OXIDE
WAVEGUIDES AT VISIBLE WAVELENGTHS
3. YEAR 3 – ITERATE WITH THE OTHER TEAM MEMBERS TO PERFECT THE DESIGN WITH FEEDBACK FROM THE
RESULTS OF THE FABRICATED STRUCTURES.
FUNDAMENTAL RESEARCH STATEMENT:
THE RESEARCH TO BE PERFORMED BY CALTECH DETAILED IN THIS PROPOSAL IS FUNDAMENTAL RESEARCH. PAM-P25-001864-SA01 Parent award context Parent award agency: Department of Defense · Defense Advanced Research Projects Agency Parent award NAICS: 541715 Parent award performance state: NC Parent award description: THE HETEROGENOUS ADAPTIVELY PRODUCED PHOTONIC INTERFACES (HAPPI) PROGRAM AIMS TO CREATE A 1000X INCREASE IN THE INFORMATION TRANSMISSION DENSITY WITHIN A MICROSYSTEM BY EXPLOITING PHOTONIC SIGNALING. View parent award on USAspending | — | $279,277 | May 1, 2025 | — – — |
| Subcontractor | Department of Defense | THE GOAL OF THIS PROJECT IS TO DEVELOP NEW APPROACHES TO DESIGN, IMPLEMENTATION, AND CONTROL OF FUNCTIONAL BIOENABLED MATERIALS USING SYNTHETIC CELLS. WE WILL BUILD ON ADVANCES IN SYNTHETIC BIOLOGY AND MOLECULAR SCIENCES THAT HAVE SUBSTANTIALLY ADVANCED OUR ABILITY TO PRODUCE GENETICALLY-PROGRAMMED SYNTHETIC CELLS FROM MOLECULAR COMPONENTS. THESE EFFORTS PROVIDE TECHNIQUES FOR THE BOTTOM-UP CONSTRUCTION OF CELL-LIKE SYSTEMS THAT CAN PROVIDE SCIENTISTS WITH NEW INSIGHTS INTO HOW NATURAL CELLS WORK AND HARNESS THE POWER OF BIOLOGY TO CREATE NANOSCALE, BIOMOLECULAR MATERIALS. UNLIKE MORE TRADITIONAL SYNTHETIC BIOLOGY APPROACHES, SYNTHETIC CELLS ARE NON-LIVING: THEY MAKE USE OF GENETIC ELEMENTS PROVIDED BY BIOLOGY, BUT THEY DO NOT REPLICATE, MUTATE, OR EVOLVE. APPLICATIONS RANGE FROM SYNTHESIS OF BIO-COMPATIBLE MATERIALS, TO ENVIRONMENTAL MONITORING AND REMEDIATION, TO SELF-ASSEMBLY OF COMPLEX MULTI-CELLULAR MACHINES. DEVELOPING FUNCTIONAL MATERIALS USING SYNTHETIC CELLS REQUIRES FUNDAMENTAL RESEARCH IN BIOLOGICAL ENGINEERING, AIMED AT MOVING FROM CREATION OF CLEVER BIOMOLECULAR DEVICES TO SYSTEMATIC SPECIFICATION, DESIGN, INTEGRATION, AND TESTING OF CIRCUITS, SUBSYSTEMS, CELLS, AND MULTI-COMPONENT SYSTEMS. THE SPECIFIC EMPHASIS IN THIS PROPOSAL IS ON ESTABLISHING THE DESIGN METHODOLOGY, CIRCUIT TECHNOLOGIES, AND SYSTEM ARCHITECTURES THAT CAN ENABLE THE DEVELOPMENT OF GENETICALLY-PROGRAMMED, FUNCTIONAL BIOMATERIALS. OUR WORK IS MOTIVATED BY BACTERIAL BIOFILMS, WHICH PROVIDE ENVIRONMENTAL PROTECTION AND STRONG ADHESION IN ADVERSE CONDITIONS. MANY BIOPOLYMERS EXTRUDED TO MAKE BIOFILMS HAVE DESIRABLE INDUSTRIAL PROPERTIES AND HAVE BEEN THE FOCUS OF RECENT EFFORTS IN SYNTHETIC BIOLOGY TO ENGINEER LIVING CELLS TO PRODUCE ADVANCED MATERIALS. HOWEVER, DETERMINING THE MINIMAL GENE SET REQUIRED FOR CELLS TO EXTRUDE ADHESIVE BIOPOLYMERS IS CHALLENGING, AS MANY PROTEINS ARE ASSOCIATED IN BIOFILM FORMATION BUT NOT ESSENTIAL. IN ADDITION, THE INTEGRATION OF FUNCTIONAL CIRCUITS THAT CAN MODULATE THE PROPERTIES OF A BIOENABLED MATERIAL BUILT FROM SYNTHETIC CELLS HAS NOT YET BEEN DEMONSTRATED. IF SUCCESSFUL, THIS RESEARCH WILL GENERATE NEW TECHNOLOGIES THAT ALLOW CREATION OF DIFFERENT TYPES OF FUNCTIONAL BIOENABLED MATERIALS THAT ARE CAPABLE OF RESPONDING TO CHANGES IN THEIR ENVIRONMENT. APPLICATIONS OF RELEVANCE TO THE ARMY INCLUDE POSSIBILITY OF DESIGNING EXTERNALLY CONTROLLED BIOENABLED MATERIALS WITH NOVEL CAPABILITIES NOT SEEN IN TRADITIONAL MATERIALS, INCLUDING THE ABILITY TO DETECT AND PRODUCE MECHANICAL, OPTICAL, AND CHEMICAL CHANGES. INITIAL WORK WILL INCLUDE IDENTIFYING AND DEVELOPING ONE OR MORE DIFFERENT TECHNICAL APPROACHES TO CREATE FUNCTIONAL MATERIALS USING SYNTHIETIC CELLS, CREATION OF SMALL MATERIAL SAMPLES FOR EXPERIMENTAL TESTING AND CHARACTERIZATION. AND EVALUATION THE OVERALL FEASIBILITY OF THE PROPOSED TECHNIQUES AND CONSIDERATION HOW TO OVERCOME THE IDENTIFIED TECHNICAL HURDLES REQUIRED FOR USE IN APPLICATIONS. KK1956-34 Parent award context Parent award agency: Department of Defense · Department of the Army Parent award NAICS: 541715 Parent award performance state: CA Parent award description: T.O. 0034-ICB-UARC-FY2023 View parent award on USAspending | W911NF19D0001USAspending | $107,262 | Mar 20, 2025 | — – — |
| Subcontractor | Department of Defense | FLOWER-BASED OPTICAL RESONATORS FOR WIDELY APPLICABLE REAGENT DETECTION 776927 Parent award context Parent award agency: Department of Defense · Department of the Army Parent award NAICS: 541715 Parent award performance state: AZ Parent award description: TOPIC AREA SECTION 7.5.A, SUBMISSION NUMBER B5-23 BROAD AGENCY ANNOUNCEMENT (BAA) TO DEVELOP A SELECTIVE, PORTABLE, AND SENSITIVE WGM CHEMICAL THREAT SENSOR THAT COULD BE ADAPTED FOR USE ON THE BATTLEFIELD, IN CLINICS, AND IN OTHER LABORATORIES. View parent award on USAspending | — | $181,500 | Oct 31, 2024 | — – — |
| Subcontractor | Department of Defense | THE GOAL OF THIS PROJECT IS TO DEVELOP NEW APPROACHES TO DESIGN, IMPLEMENTATION, AND CONTROL OF FUNCTIONAL BIOENABLED MATERIALS USING SYNTHETIC CELLS. WE WILL BUILD ON ADVANCES IN SYNTHETIC BIOLOGY AND MOLECULAR SCIENCES THAT HAVE SUBSTANTIALLY ADVANCED OUR ABILITY TO PRODUCE GENETICALLY-PROGRAMMED SYNTHETIC CELLS FROM MOLECULAR COMPONENTS. THESE EFFORTS PROVIDE TECHNIQUES FOR THE BOTTOM-UP CONSTRUCTION OF CELL-LIKE SYSTEMS THAT CAN PROVIDE SCIENTISTS WITH NEW INSIGHTS INTO HOW NATURAL CELLS WORK AND HARNESS THE POWER OF BIOLOGY TO CREATE NANOSCALE, BIOMOLECULAR MATERIALS. UNLIKE MORE TRADITIONAL SYNTHETIC BIOLOGY APPROACHES, SYNTHETIC CELLS ARE NON-LIVING: THEY MAKE USE OF GENETIC ELEMENTS PROVIDED BY BIOLOGY, BUT THEY DO NOT REPLICATE, MUTATE, OR EVOLVE. APPLICATIONS RANGE FROM SYNTHESIS OF BIO-COMPATIBLE MATERIALS, TO ENVIRONMENTAL MONITORING AND REMEDIATION, TO SELF-ASSEMBLY OF COMPLEX MULTI-CELLULAR MACHINES. DEVELOPING FUNCTIONAL MATERIALS USING SYNTHETIC CELLS REQUIRES FUNDAMENTAL RESEARCH IN BIOLOGICAL ENGINEERING, AIMED AT MOVING FROM CREATION OF CLEVER BIOMOLECULAR DEVICES TO SYSTEMATIC SPECIFICATION, DESIGN, INTEGRATION, AND TESTING OF CIRCUITS, SUBSYSTEMS, CELLS, AND MULTI-COMPONENT SYSTEMS. THE SPECIFIC EMPHASIS IN THIS PROPOSAL IS ON ESTABLISHING THE DESIGN METHODOLOGY, CIRCUIT TECHNOLOGIES, AND SYSTEM ARCHITECTURES THAT CAN ENABLE THE DEVELOPMENT OF GENETICALLY-PROGRAMMED, FUNCTIONAL BIOMATERIALS. OUR WORK IS MOTIVATED BY BACTERIAL BIOFILMS, WHICH PROVIDE ENVIRONMENTAL PROTECTION AND STRONG ADHESION IN ADVERSE CONDITIONS. MANY BIOPOLYMERS EXTRUDED TO MAKE BIOFILMS HAVE DESIRABLE INDUSTRIAL PROPERTIES AND HAVE BEEN THE FOCUS OF RECENT EFFORTS IN SYNTHETIC BIOLOGY TO ENGINEER LIVING CELLS TO PRODUCE ADVANCED MATERIALS. HOWEVER, DETERMINING THE MINIMAL GENE SET REQUIRED FOR CELLS TO EXTRUDE ADHESIVE BIOPOLYMERS IS CHALLENGING, AS MANY PROTEINS ARE ASSOCIATED IN BIOFILM FORMATION BUT NOT ESSENTIAL. IN ADDITION, THE INTEGRATION OF FUNCTIONAL CIRCUITS THAT CAN MODULATE THE PROPERTIES OF A BIOENABLED MATERIAL BUILT FROM SYNTHETIC CELLS HAS NOT YET BEEN DEMONSTRATED. IF SUCCESSFUL, THIS RESEARCH WILL GENERATE NEW TECHNOLOGIES THAT ALLOW CREATION OF DIFFERENT TYPES OF FUNCTIONAL BIOENABLED MATERIALS THAT ARE CAPABLE OF RESPONDING TO CHANGES IN THEIR ENVIRONMENT. APPLICATIONS OF RELEVANCE TO THE ARMY INCLUDE POSSIBILITY OF DESIGNING EXTERNALLY CONTROLLED BIOENABLED MATERIALS WITH NOVEL CAPABILITIES NOT SEEN IN TRADITIONAL MATERIALS, INCLUDING THE ABILITY TO DETECT AND PRODUCE MECHANICAL, OPTICAL, AND CHEMICAL CHANGES. INITIAL WORK WILL INCLUDE IDENTIFYING AND DEVELOPING ONE OR MORE DIFFERENT TECHNICAL APPROACHES TO CREATE FUNCTIONAL MATERIALS USING SYNTHIETIC CELLS, CREATION OF SMALL MATERIAL SAMPLES FOR EXPERIMENTAL TESTING AND CHARACTERIZATION. AND EVALUATION THE OVERALL FEASIBILITY OF THE PROPOSED TECHNIQUES AND CONSIDERATION HOW TO OVERCOME THE IDENTIFIED TECHNICAL HURDLES REQUIRED FOR USE IN APPLICATIONS. KK1956-34 Parent award context Parent award agency: Department of Defense · Department of the Army Parent award NAICS: 541715 Parent award performance state: CA Parent award description: T.O. 0034-ICB-UARC-FY2023 View parent award on USAspending | W911NF19D0001USAspending | $107,261 | Sep 10, 2024 | — – — |
| Subcontractor | Department of Energy | CALTECH-STANDALONE-ITEM LEVEL-R AND D CW52194 Parent award context Parent award agency: Department of Energy · Department of Energy Parent award NAICS: 561210 Parent award performance state: NM Parent award description: IGF::CL::IGF COMPETITION FOR MANAGEMENT AND OPERATION OF LOS ALAMOS NATIONAL LABORATORY View parent award on USAspending | — | $350,000 | Jun 6, 2024 | — – — |
| Subcontractor | Department of Energy | Q-NET 713558 Parent award context Parent award agency: Department of Energy · Department of Energy Parent award NAICS: 541715 Parent award performance state: IL Parent award description: MANAGEMENT AND OPERATING CONTRACT FOR THE FERMI NATIONAL ACCELERATOR LABORATORY (FNAL) View parent award on USAspending | — | $1,204,377 | Apr 16, 2024 | — – — |
| Subcontractor | Department of Defense | THE GOAL OF THIS PROJECT IS TO DEVELOP NEW APPROACHES TO DESIGN, IMPLEMENTATION, AND CONTROL OF FUNCTIONAL BIOENABLED MATERIALS USING SYNTHETIC CELLS. WE WILL BUILD ON ADVANCES IN SYNTHETIC BIOLOGY AND MOLECULAR SCIENCES THAT HAVE SUBSTANTIALLY ADVANCED OUR ABILITY TO PRODUCE GENETICALLY-PROGRAMMED SYNTHETIC CELLS FROM MOLECULAR COMPONENTS. THESE EFFORTS PROVIDE TECHNIQUES FOR THE BOTTOM-UP CONSTRUCTION OF CELL-LIKE SYSTEMS THAT CAN PROVIDE SCIENTISTS WITH NEW INSIGHTS INTO HOW NATURAL CELLS WORK AND HARNESS THE POWER OF BIOLOGY TO CREATE NANOSCALE, BIOMOLECULAR MATERIALS. UNLIKE MORE TRADITIONAL SYNTHETIC BIOLOGY APPROACHES, SYNTHETIC CELLS ARE NON-LIVING: THEY MAKE USE OF GENETIC ELEMENTS PROVIDED BY BIOLOGY, BUT THEY DO NOT REPLICATE, MUTATE, OR EVOLVE. APPLICATIONS RANGE FROM SYNTHESIS OF BIO-COMPATIBLE MATERIALS, TO ENVIRONMENTAL MONITORING AND REMEDIATION, TO SELF-ASSEMBLY OF COMPLEX MULTI-CELLULAR MACHINES. DEVELOPING FUNCTIONAL MATERIALS USING SYNTHETIC CELLS REQUIRES FUNDAMENTAL RESEARCH IN BIOLOGICAL ENGINEERING, AIMED AT MOVING FROM CREATION OF CLEVER BIOMOLECULAR DEVICES TO SYSTEMATIC SPECIFICATION, DESIGN, INTEGRATION, AND TESTING OF CIRCUITS, SUBSYSTEMS, CELLS, AND MULTI-COMPONENT SYSTEMS. THE SPECIFIC EMPHASIS IN THIS PROPOSAL IS ON ESTABLISHING THE DESIGN METHODOLOGY, CIRCUIT TECHNOLOGIES, AND SYSTEM ARCHITECTURES THAT CAN ENABLE THE DEVELOPMENT OF GENETICALLY-PROGRAMMED, FUNCTIONAL BIOMATERIALS. OUR WORK IS MOTIVATED BY BACTERIAL BIOFILMS, WHICH PROVIDE ENVIRONMENTAL PROTECTION AND STRONG ADHESION IN ADVERSE CONDITIONS. MANY BIOPOLYMERS EXTRUDED TO MAKE BIOFILMS HAVE DESIRABLE INDUSTRIAL PROPERTIES AND HAVE BEEN THE FOCUS OF RECENT EFFORTS IN SYNTHETIC BIOLOGY TO ENGINEER LIVING CELLS TO PRODUCE ADVANCED MATERIALS. HOWEVER, DETERMINING THE MINIMAL GENE SET REQUIRED FOR CELLS TO EXTRUDE ADHESIVE BIOPOLYMERS IS CHALLENGING, AS MANY PROTEINS ARE ASSOCIATED IN BIOFILM FORMATION BUT NOT ESSENTIAL. IN ADDITION, THE INTEGRATION OF FUNCTIONAL CIRCUITS THAT CAN MODULATE THE PROPERTIES OF A BIOENABLED MATERIAL BUILT FROM SYNTHETIC CELLS HAS NOT YET BEEN DEMONSTRATED. IF SUCCESSFUL, THIS RESEARCH WILL GENERATE NEW TECHNOLOGIES THAT ALLOW CREATION OF DIFFERENT TYPES OF FUNCTIONAL BIOENABLED MATERIALS THAT ARE CAPABLE OF RESPONDING TO CHANGES IN THEIR ENVIRONMENT. APPLICATIONS OF RELEVANCE TO THE ARMY INCLUDE POSSIBILITY OF DESIGNING EXTERNALLY CONTROLLED BIOENABLED MATERIALS WITH NOVEL CAPABILITIES NOT SEEN IN TRADITIONAL MATERIALS, INCLUDING THE ABILITY TO DETECT AND PRODUCE MECHANICAL, OPTICAL, AND CHEMICAL CHANGES. INITIAL WORK WILL INCLUDE IDENTIFYING AND DEVELOPING ONE OR MORE DIFFERENT TECHNICAL APPROACHES TO CREATE FUNCTIONAL MATERIALS USING SYNTHIETIC CELLS, CREATION OF SMALL MATERIAL SAMPLES FOR EXPERIMENTAL TESTING AND CHARACTERIZATION. AND EVALUATION THE OVERALL FEASIBILITY OF THE PROPOSED TECHNIQUES AND CONSIDERATION HOW TO OVERCOME THE IDENTIFIED TECHNICAL HURDLES REQUIRED FOR USE IN APPLICATIONS. KK1956-34 Parent award context Parent award agency: Department of Defense · Department of the Army Parent award NAICS: 541715 Parent award performance state: CA Parent award description: T.O. 0034-ICB-UARC-FY2023 View parent award on USAspending | W911NF19D0001USAspending | $173,234 | Apr 3, 2024 | — – — |
| Subcontractor | Department of Defense | THE GOAL OF THIS PROJECT IS TO DEVELOP NEW APPROACHES TO DESIGN, IMPLEMENTATION, AND CONTROL OF FUNCTIONAL BIOENABLED MATERIALS USING SYNTHETIC CELLS. WE WILL BUILD ON ADVANCES IN SYNTHETIC BIOLOGY AND MOLECULAR SCIENCES THAT HAVE SUBSTANTIALLY ADVANCED OUR ABILITY TO PRODUCE GENETICALLY-PROGRAMMED SYNTHETIC CELLS FROM MOLECULAR COMPONENTS. THESE EFFORTS PROVIDE TECHNIQUES FOR THE BOTTOM-UP CONSTRUCTION OF CELL-LIKE SYSTEMS THAT CAN PROVIDE SCIENTISTS WITH NEW INSIGHTS INTO HOW NATURAL CELLS WORK AND HARNESS THE POWER OF BIOLOGY TO CREATE NANOSCALE, BIOMOLECULAR MATERIALS. UNLIKE MORE TRADITIONAL SYNTHETIC BIOLOGY APPROACHES, SYNTHETIC CELLS ARE NON-LIVING: THEY MAKE USE OF GENETIC ELEMENTS PROVIDED BY BIOLOGY, BUT THEY DO NOT REPLICATE, MUTATE, OR EVOLVE. APPLICATIONS RANGE FROM SYNTHESIS OF BIO-COMPATIBLE MATERIALS, TO ENVIRONMENTAL MONITORING AND REMEDIATION, TO SELF-ASSEMBLY OF COMPLEX MULTI-CELLULAR MACHINES. DEVELOPING FUNCTIONAL MATERIALS USING SYNTHETIC CELLS REQUIRES FUNDAMENTAL RESEARCH IN BIOLOGICAL ENGINEERING, AIMED AT MOVING FROM CREATION OF CLEVER BIOMOLECULAR DEVICES TO SYSTEMATIC SPECIFICATION, DESIGN, INTEGRATION, AND TESTING OF CIRCUITS, SUBSYSTEMS, CELLS, AND MULTI-COMPONENT SYSTEMS. THE SPECIFIC EMPHASIS IN THIS PROPOSAL IS ON ESTABLISHING THE DESIGN METHODOLOGY, CIRCUIT TECHNOLOGIES, AND SYSTEM ARCHITECTURES THAT CAN ENABLE THE DEVELOPMENT OF GENETICALLY-PROGRAMMED, FUNCTIONAL BIOMATERIALS. OUR WORK IS MOTIVATED BY BACTERIAL BIOFILMS, WHICH PROVIDE ENVIRONMENTAL PROTECTION AND STRONG ADHESION IN ADVERSE CONDITIONS. MANY BIOPOLYMERS EXTRUDED TO MAKE BIOFILMS HAVE DESIRABLE INDUSTRIAL PROPERTIES AND HAVE BEEN THE FOCUS OF RECENT EFFORTS IN SYNTHETIC BIOLOGY TO ENGINEER LIVING CELLS TO PRODUCE ADVANCED MATERIALS. HOWEVER, DETERMINING THE MINIMAL GENE SET REQUIRED FOR CELLS TO EXTRUDE ADHESIVE BIOPOLYMERS IS CHALLENGING, AS MANY PROTEINS ARE ASSOCIATED IN BIOFILM FORMATION BUT NOT ESSENTIAL. IN ADDITION, THE INTEGRATION OF FUNCTIONAL CIRCUITS THAT CAN MODULATE THE PROPERTIES OF A BIOENABLED MATERIAL BUILT FROM SYNTHETIC CELLS HAS NOT YET BEEN DEMONSTRATED. IF SUCCESSFUL, THIS RESEARCH WILL GENERATE NEW TECHNOLOGIES THAT ALLOW CREATION OF DIFFERENT TYPES OF FUNCTIONAL BIOENABLED MATERIALS THAT ARE CAPABLE OF RESPONDING TO CHANGES IN THEIR ENVIRONMENT. APPLICATIONS OF RELEVANCE TO THE ARMY INCLUDE POSSIBILITY OF DESIGNING EXTERNALLY CONTROLLED BIOENABLED MATERIALS WITH NOVEL CAPABILITIES NOT SEEN IN TRADITIONAL MATERIALS, INCLUDING THE ABILITY TO DETECT AND PRODUCE MECHANICAL, OPTICAL, AND CHEMICAL CHANGES. INITIAL WORK WILL INCLUDE IDENTIFYING AND DEVELOPING ONE OR MORE DIFFERENT TECHNICAL APPROACHES TO CREATE FUNCTIONAL MATERIALS USING SYNTHIETIC CELLS, CREATION OF SMALL MATERIAL SAMPLES FOR EXPERIMENTAL TESTING AND CHARACTERIZATION. AND EVALUATION THE OVERALL FEASIBILITY OF THE PROPOSED TECHNIQUES AND CONSIDERATION HOW TO OVERCOME THE IDENTIFIED TECHNICAL HURDLES REQUIRED FOR USE IN APPLICATIONS. KK1956-34 Parent award context Parent award agency: Department of Defense · Department of the Army Parent award NAICS: 541715 Parent award performance state: CA Parent award description: T.O. 0034-ICB-UARC-FY2023 View parent award on USAspending | W911NF19D0001USAspending | $162,243 | Oct 17, 2023 | — – — |
| Subcontractor | Department of Defense | R&D-SCHOOLS, NON-MIT 7000582930 Parent award context Parent award agency: Department of Defense · Department of the Air Force Parent award NAICS: 541712 Parent award performance state: MA Parent award description: IGF::CT::IGF TASK ORDER 0001 FOR DOD LINE FUNDING View parent award on USAspending | FA870215D0001USAspending | $75,000 | May 30, 2023 | — – — |
| Subcontractor | Department of Defense | THE GOAL OF THIS ICB ADVANCED SCIENTIFIC RESEARCH PROJECT IS TO DEVELOP A NEW BASIC BUILDING BLOCK, CALLED A €œBIOHYBRID-
VOXEL€Ͽ½ (BHV) TO EVENTUALLY ORGANIZE INTO BIO-HYBRID METAMATERIALS WITH MACROSCOPIC DIMENSIONS. THESE BHVS WILL BE COMPRISED OF AN INORGANIC (I.E. METAL OXIDE) CORE UNIT CELL (I.E. DODECAHEDRON) AND A LOW-MOLECULAR WEIGHT PROTEIN PASSIVATION (LAMININ, FIBRONECTIN, FERRITIN). THE PROTEIN COATINGS WILL BE DESIGNED TO ADHERE TO THE DNA ORIGAMI PATTERNS ON A SUBSTRATE, WHEREBY THE DNA STRANDS SELF-ASSEMBLE INTO USER-DEFINED SHAPES WITH NANOSCALE FEATURES. WE ARE DEVELOPING A METHOD OF ORIGAMI PATTERN FORMATION AND TRANSFER THAT PRESERVES THE SIZE AND RESOLUTION OF THE SHAPES. THESE BIO-HYBRID VOXELS WILL PROBE THE HYPOTHESIS WHETHER COLLECTIVE ASSEMBLY OF BIOMOLECULES AND TESSELLATION OF THE HYBRID-VOXELS VIA FORMING DIRECTIONAL BONDS THROUGH DNA HYBRIDIZATION WILL EXTEND 3D BIO-HYBRID UNIT CELLS INTO PRINTABLE HYDROGEL NETWORKS. COMBINED WITH THE SUBSTRATE SURFACE EFFECTS MEDIATED BY DNA ARCHITECTURES, THESE SCAFFOLDS WILL EXTEND THE DIRECTED SELF-ASSEMBLY TO THE LONG-RANGE ORDERING THAT HAS ALREADY BEEN SUCCESSFULLY DEMONSTRATED IN 2D TO ADDITIVE MANUFACTURING IN 3D. ADDITIVE MANUFACTURING HAS ALREADY TRANSFORMED MATERIALS SCIENCE IN AREAS RANGING FROMOUR ABILITY TO PROTOTYPE POLYMERS, CERAMICS, AND METALS TO THE CUSTOMIZATION OF PRODUCTS FROM AUTOMOTIVE PARTS TO SPORTS SHOES. IT IS A CORE ELEMENT OF THE FOURTH INDUSTRIAL REVOLUTION, WITH A LONG-STANDING EXPECTED IMPACT ON THE MANUFACTURING WORLD. A KEY ADVANTAGE OF AM IS ITS CONTROL OVER COMPLEX SHAPES OF PRINTED MATERIALS AT THE MACROSCALE IS UNMATCHED BY COMPETING MANUFACTURING PROCESSES, A KEY DRAWBACK IS THAT THE UNDERLYING MOLECULAR COMPLEXITY OF THE PRINTABLE MATERIALS IS STILL RELATIVELY LOW.1,3 THE FUNCTIONALITY OF THE RESULTING MATERIALS, THEREFORE, EXPECTEDLY LAGS FAR BEHIND THAT OF BIOLOGICAL SYSTEMS. THIS PROPOSED WORK IS EXPECTED TO SUBSTANTIALLY SHORTEN THIS GAP BY INTRODUCING A COMBINATION BIO-ENABLED MATERIALS CONCEPTS INTO ADDITIVE MANUFACTURING INCLUDING (I) PROGRAMMABLE SELF-ASSEMBLY OF BIOMACROMOLECULE-INORGANIC BUILDING BLOCKS (BIO-HYBRID VOXELS) AND (II) DIRECTED SELF-ASSEMBLY OF SUCH BHVS IN 3D-SCULPTING OF HYDROGEL RESINS. KK1956-30 Parent award context Parent award agency: Department of Defense · Department of the Army Parent award NAICS: 541715 Parent award performance state: CA Parent award description: T.O. 0030 -ICB-UARC-FY 2022 NS UARC TASK ORDER. View parent award on USAspending | W911NF19D0001USAspending | $300,000 | Dec 7, 2022 | — – — |
| Subcontractor | Department of Defense | ENVIRONMENTAL CHEMICALS, NARCOTICS AND PHARMACEUTICALS INFLUENCE BEHAVIORAL STATES IN A THRESHOLD-DEPENDENT MANNER
THE NEUROBIOLOGICAL MECHANISMS UNDERLYING SUCH THRESHOLDS REMAIN POORLY UNDERSTOOD, BUT COULD BE HARNESSED TO MANIPULATE PHYSIOLOGY, BEHAVIOR AND PSYCHOLOGY IN DESIRABLE WAYS FOR BOTH STRATEGIC AND THERAPEUTIC GOALS. DUE TO THE COMPLEXITY AND CHALLENGES POSED BY STUDYING THE HUMAN NERVOUS SYSTEM, FUNDAMENTAL INSIGHT MAY BE GAINED FROM
SIMPLER BUT HIGHLY TRACTABLE ANIMAL MODELS, WHERE DEFINED COMPOUNDS EVOKE DRAMATIC BEHAVIORAL RESPONSES THAT ARE
BOTH STEREOTYPED AND QUANTIFIABLE. SUCH SYSTEMS MAY YIELD INTUITIVE AND GENERAL PARADIGMS THAT CONNECT CHEMOSENSORY
INPUT TO BEHAVIORAL OUTPUT.
ANTS REPRESENT A POWERFUL SYSTEM TO EXPLORE THE RELATIONSHIP BETWEEN CHEMISTRY AND BEHAVIOR BECAUSE BOTH THEIR INDIVIDUAL AND COLLECTIVE BEHAVIORS ARE DETERMINED BY ACUTE SENSITIVITY TO SMALL MOLECULE COMPOUNDS, IN PARTICULAR, A
CLASS OF CHEMICALS KNOWN AS CUTICULAR HYDROCARBONS (CHCS) [2,3]. CHCS ARE VERY-LONG-CHAIN ALKANES AND ALKENES THAT ARE SECRETED ONTO THE BODY AS A MIXTURE ENCODING A SIGNATURE OF COLONY IDENTITY. ANTS RECOGNIZE AND ACCEPT MEMBERS OF THEIR OWN COLONY BASED ON SIMILAR CHC PROFILES, EMPLOYING A TEMPLATE MATCHING MECHANISM. IN CONTRAST, DISCREPANCIES IN THE CHC PROFILE TRIGGER EXTREME CHANGES IN BEHAVIORAL STATE. ANTS ARE INNATELY PROGRAMMED TO ATTACK ORGANISMS THAT DO NOT MATCH THEIR COLONY'S CHC TEMPLATE, INITIATING BOTH INDIVIDUAL AGGRESSION AND THE RECRUITMENT OF OTHER WORKERS TO MOUNT A COLLECTIVE RESPONSE. THIS STARK BEHAVIORAL RESPONSE THRESHOLD DISTINGUISHES ANTS AS A POTENTIALLY VALUABLE STUDY SYSTEM TO EXAMINE HOW THE DETECTION OF MINOR CHEMICAL TRACES CAN ELICIT MAJOR CHANGES IN BEHAVIORAL STATE. HARNESSING THIS SYSTEM, WE PROPOSE TO ENGINEER A CHEMICALLY INVISIBLE COLONY INTRUDER€€?A CHEMICAL BLANK SLATE ORGANISM ONTO WHICH CHCS CAN BE EXPERIMENTALLY REINTRODUCED. USING THIS APPROACH, WE WILL DETERMINE HOW VARYING THE IDENTITY AND QUANTITY OF SPECIFIC CHCS OR MIXTURES DELIVERED ONTO THE BODY SURFACE TRIGGERS INDIVIDUAL AND COLLECTIVE AGGRESSION RESPONSES IN ANTS. USING TOOLS FOR CRISPR GENE MANIPULATION WE WILL ENGINEER A FREE-LIVING ROVE BEETLE€€?DALOTIA CORIARIA€€?INTO A STEALTH IMPOSTOR (FIG. 1A). WITH PLATFORMS FOR AUTOMATED BEHAVIORAL ANALYSIS PIONEERED BY MY LABORATORY, WE WILL EXAMINE STEALTH DALOTIA'S ABILITY TO INFILTRATE, SURVIVE AND INTERACT INSIDE ANT COLONIES, QUANTIFYING BEHAVIORAL RESPONSES OF ANTS TOWARD THE IMPOSTOR WHEN IT IS USED AS A VEHICLE FOR ANT CHCS OF VARYING LEVELS AND COMBINATIONS (FIG. 1B). SIMULTANEOUSLY, WE WILL QUANTIFY THE BEHAVIORAL ACCLIMATION OF BEETLES INSIDE ANT COLONIES AS THEIR CHEMICAL RESEMBLANCE TO THE HOST ANT IS EXPERIMENTALLY INCREASED. IN THIS WAY, WE WILL MEASURE HOW BEHAVIORAL RESPONSES OF EACH PARTNER CHANGE ACROSS A CONTINUUM OF CHEMICAL DISSIMILARITY. USING THESE EMPIRICAL DATA, WE WILL MODEL HOW RELATIVE AND ABSOLUTE CHC DISCREPANCIES ARE USED BY EACH PARTNER SPECIES TO COMPUTE BEHAVIORAL RESPONSES OF DIFFERENT MAGNITUDES AND DURATIONS. THIS WORK WILL SET THE SET STAGE FOR FUTURE ANALYSES OF THE UNDERLYING SENSORIMOTOR COMPUTATIONS IN EACH PARTNER SPECIES THAT ASSIGN CHEMOSENSORY MEASUREMENTS TO THRESHOLD BEHAVIORAL OUTPUTS. KK1956-31 Parent award context Parent award agency: Department of Defense · Department of the Army Parent award NAICS: 541715 Parent award performance state: CA Parent award description: T.O. 0031 -ICB-UARC-FY 2022. NS UARC TASK ORDER. View parent award on USAspending | W911NF19D0001USAspending | $300,000 | Dec 7, 2022 | — – — |
| Subcontractor | Department of Defense | R&D-SCHOOLS, NON-MIT 7000545602 Parent award context Parent award agency: Department of Defense · Department of the Air Force Parent award NAICS: 541712 Parent award performance state: MA Parent award description: IGF::CT::IGF TASK ORDER 0001 FOR DOD LINE FUNDING View parent award on USAspending | FA870215D0001USAspending | $100,000 | Apr 22, 2022 | — – — |
| Subcontractor | Department of Defense | TOWARD THE GOAL OF MAKING PREPARATIVE-SCALE QUANTITIES OF THESE COMPOUNDS, WE BEGAN ENGINEERING P411 B10 BY DIRECTED EVOLUTION TO INCREASE THE YIELD AND SELECTIVITY OF EACH OF THE TWO BICYCLOBUTANES. SITE-SATURATION MUTAGENESIS OF KEY RESIDUES IN THE P411 B10 ACTIVE SITE LED TO SEPARATE LINEAGES FOR EACH BICYCLOBUTANE. THREE ROUNDS OF EVOLUTION GENERATED VARIANTS EXHIBITING 6:1 AND 12:1 SELECTIVITY FOR THE EXO-EXO AND EXO-ENDO BICYCLOBUTANES, RESPECTIVELY, WITH OVERALL ANALYTICAL YIELDS APPROACHING 5€€Œ10%. MOVING FORWARD, WE ARE USING ERROR-PRONE PCR TO EXPLORE SEQUENCE SPACE FOR IMPROVEMENTS IN A MORE RANDOMIZED FASHION. FURTHER IMPROVEMENTS IN BOTH ACTIVITY AND SELECTIVITY WILL BE NECESSARY TO ACHIEVE PRODUCTION AT SCALE. WE IDENTIFIED ANOTHER ENZYME FROM OUR COLLECTION, P411 C6, THAT PRODUCES A HIGHER QUANTITY OF THE CYCLOPROPANE WITHOUT ANY SIGNIFICANT QUANTITIES OF EITHER BICYCLOBUTANE. AT PRESENT, WE ARE DEVELOPING A SCALE-UP PROCEDURE OF THIS REACTION TO ACHIEVE THE GRAM-SCALE QUANTITIES REQUESTED BY DR. SABATINI. BRIEFLY, WE PROPOSE TO EXPRESS THE P411S BY CONVENTIONAL CULTURING TECHNIQUE S AND PREPARING REACTIONS IN WHOLE-CELL OR LYOPHILIZED LYSATE FORMATS IN BATCH REACTOR SYSTEMS OF SUITABLE SIZE. THE FINAL PRODUCTS WILL BE PURIFIED BY A SEQUENCE OF CELL FILTRATION, EXTRACTION INTO ORGANIC SOLVENTS, AND PREPARATIVE-SCALE DISTILLATION. THE OPTIMIZED PROCESS SHOULD BE, IN PRINCIPLE, SCALABLE EVEN INTO KILOGRAM RANGE. INCREASING THE STABILITY OF THE PROTEIN CATALYST (AIM 2) IS ALSO EXPECTED TO IMPROVE PERFORMANCE OF THE PROCESS. WE PLAN TO CRAFT A SYSTEM OF SCREENING, ENGINEERING, AND LARGE-SCALE PREPARATIONS FOR THESE COMPOUNDS AND OTHER TARGET COMPOUNDS THAT ARE OF INTEREST TO ARL RESEARCHERS. COMPOUNDS OF POTENTIAL INTEREST INCLUDE BICYCLOBUTANES AND CYCLOPROPENES, AZETIDINES AND FUNCTIONALIZED CARBORANES, IN ADDITION OTHER MOLECULAR STRUCTURES THAT WE MAY BE ABLE TO ACCESS ENZYMATICALLY.
THE SUBSTANTIAL NUMBER OF MUTATIONS ACCRUED OVER THE COURSE OF ENGINEERING CYTOCHROME P411 ENZYMES FOR NEW ACTIVITIES HAS DEGRADED CATALYST STABILITY AND UTILITY AT PROCESS SCALE, BECAUSE THESE PROPERTIES COULD NOT BE MONITORED DURING SCREENING FOR ENHANCED ACTIVITY. CARBENE TRANSFERASES EXHIBITING GREATER STABILITY AND TOLERANCE TO PROCESS CONDITIONS WILL ENABLE US TO IMPLEMENT LARGER-SCALE TRANSFORMATIONS TO MAKE ENERGETIC COMPOUNDS AND OTHER MATERIALS OF INTEREST TO THE ARMY. THE OBJECTIVE OF THIS AIM IS TO USE SCREENING OF CARBENE TRANSFERASE MUTANT LIBRARIES IN CONCERT WITH MACHINE LEARNING (ML) TO ENGINEER VARIANTS THAT ARE BOTH HIGHLY ACTIVE AND HIGHLY STABLE. WE EXPECT THAT BENEFICIAL MUTATIONS IDENTIFIED DURING THIS EFFORT WILL BE USEFUL ACROSS THE WHOLE CARBENE TRANSFERASE, AND POSSIBLY ALSO THE NITRENE TRANSFERASE, PLATFORM. THIS EFFORT WILL ALSO DEMONSTRATE A POWERFUL NEW ML-GUIDED DIRECTED EVOLUTION APPROACH TO ENGINEERING BIOCATALYSTS. BRIEFLY, WE WILL USE A SYSTEMATIC €œTILING€Ͽ½ APPROACH IN WHICH THE GENE IS DIVIDED INTO SECTIONS (SIZE SUITABLE FOR SHORT-READ SEQUENCING) AND THE EFFECTS OF SINGLE MUTATIONS IN THOSE SECTIONS ARE ASSESSED. FOR EACH VARIANT, TOTAL PROTEIN EXPRESSION, THERMAL STABILITY, AND C€€ŒH INSERTION ACTIVITY WILL BE MEASURED. A NEW, LOW-COST NEXT- GENERATION SEQUENCING METHOD WE DEVELOPED RECENTLY WILL BE USED TO SEQUENCE EACH SCREENED VARIANT, SO THAT OBSERVED CHANGES IN PROPERTIES CAN BE LINKED DIRECTLY TO SPECIFIC MUTATIONS. THIS DATASET IS THEN USED IN ML TO PREDICT BENEFICIAL COMBINATIONS OF MUTATIONS THAT WILL BE SCREENED IN THE SAME MANNER. WE EXPECT THAT FIRST RECOMBINING WITHIN TILES, THEN ACROSS TILES, AND ULTIMATELY ACROSS THE ENTIRE ENZYME WILL RESULT IN HIGHLY STABLE AND CATALYTICALLY ACTIVE CARBENE TRANSFERASES THAT WE CAN USE IN LARGER-SCALE REACTIONS AND UNDER A VARIETY OF REACTION CONDITIONS. THIS WILL BE A RELIABLE METHOD FOR ENGINEERING PROCESS-SUITABLE BIOCATALYSTS. KK1956-24 Parent award context Parent award agency: Department of Defense · Department of the Army Parent award NAICS: 541715 Parent award performance state: CA Parent award description: TASK ORDER 24- (74393 LS-ICB) View parent award on USAspending | W911NF19D0001USAspending | $450,000 | Jan 6, 2022 | — – — |
| Subcontractor | Department of Defense | GOALS: THE GOAL OF THIS PROJECT IS TO DEVELOP GENETIC CIRCUITS THAT CAN BE IMPLEMENTED IN ENGINEERED MICROBES OPERATING IN (LABORATORY-BASED) SOIL ENVIRONMENTS THAT ARE ABLE TO SENSE AND MANIPULATE THE CONCENTRATION OF SMALL MOLECULES PRESENT IN THE SOIL. WE PLAN TO USE PHOSPHORUS AS OUR INITIAL MOLECULE OF INTEREST, AS A MODEL FOR OTHER CHEMICAL SPECIES PRESENT IN SOILS.
SPECIFIC PROJECT OBJECTIVES:
TASK 1: USE OF ENGINEERED MICROORGANISMS FOR SENSING AND CHARACTERIZING RHIZOSPHERE PROPERTIES. A KEY ELEMENT OF CHARACTERIZATION AND REMEDIATION OF SOIL ECOLOGIES WILL BE DEVELOPING AND UNDERSTANDING OF THE BIOLOGY AND CHEMISTRY OF SOIL ECOSYSTEMS. CULTURE AND SEQUENCING CAN PROVIDE A BROAD OUTLINE OF WHAT IS IN THE RHIZOSPHERE. IN SITU HYBRIDIZATION CAN CONTRIBUTE TO PROVIDE SOME SPATIAL INFORMATION FOR SPECIFIC SPECIES AND THE GENES THEY ARE EXPRESSING. HOWEVER, MUCH OF WHAT WE WANT TO KNOW INVOLVES UNDERSTANDING THE ROLES OF PARTICULAR GENES, AND THE LEVELS OF NUTRIENTS AND METABOLITES IN SPECIFIC SPECIES IN SPECIFIC MICROENVIRONMENTS. WHILE MANY COMPOUNDS ARE FOUND IN SOILS, ONE OF THE MOST IMPORTANT IS PHOSPHATE, A VITAL MACRONUTRIENT. RECENTLY, WE HAVE DISCOVERED THAT DIVERSE SOIL BACTERIA PRODUCE REDOX-ACTIVE ANTIBIOTICS (E.G. PHENAZINES) IN RESPONSE TO PHOSPHORUS LIMITATIONS; PHENAZINES HELP MAKE PHOSPHORUS MORE BIOAVAILABLE BY CATALYZING THE REDUCTIVE DISSOLUTION OF MINERALS TO WHICH PHOSPHORUS IS ADSORBED. BECAUSE PHENAZINES BIOSYNTHESIS IS GENETICALLY TRACTABLE AND PHENAZINES CAN BE ELECTROCHEMICALLY DETECTED, THERE IS AN EXCITING OPPORTUNITY TO BUILD ON THESE DISCOVERIES USING SYNTHETIC BIOLOGY TO DETECT PHOSPHORUS CONCENTRATION AS AN EXEMPLAR FOR IN SITU DETECTION OF OTHER CHEMICAL SPECIES. SPECIES-SPECIFIC TRANSGENESIS AND THE CREATION OF REPORTERS AND BIOSENSORS WILL CONTRIBUTE TO THIS GOAL, MORE BROADLY SHOWCASING HOW SYNTHETIC BIOLOGY CAN BE APPLIED TO SENSE COMPOUNDS OF INTEREST IN SOILS.
TASK 2: USE OF ENGINEERED MICROORGANISMS TO DETECT, RESPOND, AND MANIPULATE RHIZOSPHERE CONDITIONS. IN ADDITION TO CHARACTERIZATION, WE ULTIMATELY WANT TO BE ABLE TO PERTURB THE RHIZOSPHERE TO ENHANCE DESIRED CHARACTERISTICS SUCH AS SOIL MATERIAL PROPERTIES OR TO REMEDIATE SPILLS THAT MAY HAVE BEEN AFFECTED BY TOXINS. ENGINEERED MICROORGANISMS PROVIDE A MECHANISM FOR DETECTING LOCAL ENVIRONMENTAL CONDITIONS AND THEN RESPONDING TO THESE CONDITIONS BY SYNTHESIZING AND EXPORTING SMALL MOLECULES OR PROTEINS THAT MODULATE THE BIOLOGICAL AND CHEMICAL STATE OF THE SOIL. THIS WORK WILL INVOLVE INTRODUCTION OF NOVEL EXTANT WILDTYPE MEMBERS OF OTHER SPECIES INTO ENVIRONMENTS, AND CHARACTERIZATION OF THEIR FATE AND INFLUENCE ON OTHER SPECIES. IT WILL ALSO INVOLVE GENETIC MODIFICATION, CREATION OF CIRCUITS, AND ENGINEERING OF COOPERATIVE AND COMPETITIVE INTERACTIONS THAT FUNCTION IN THE SOIL ENVIRONMENT. IN PARTICULAR, WE PLAN TO DEMONSTRATE THE ABILITY TO SENSE AND RESPOND TO THE PRESENCE OF PHOSPHORUS, AGAIN AS AN EXEMPLAR OF MANIPULATION OF COMPOUNDS OF INTEREST IN SOILS.
DELIVERABLES: (1) PROTOCOLS TO DESIGN AND BUILD DIAGNOSTICS FOR DETECTION OF CHEMICALS USING ENGINEERED SOIL MICROBES. (2) REPORTS DOCUMENTING CHARACTERIZATION AND MANIPULATION OF CHEMICALS IN LABORATORY SOIL SAMPLES. (3) COLLABORATIVE RESEARCH PLANNING AND TECHNOLOGY TRANSITION WORKSHOPS BETWEEN THE ARMY'S ICB, ERDC AND THE ARMY. ALL WORK PERFORMED WILL BE DOCUMENTED IN THE FORM OF PUBLISHED PAPERS AND/OR OPENLY AVAILABLE TECHNICAL REPORTS. PROTOCOLS, CHARACTERIZATION DATA, AND PRODUCTION CODE WILL BE ARCHIVED IN PUBLICLY ACCESSIBLE DATA REPOSITORIES. CELL STRAINS, EXTRACTS, AND GENETIC CIRCUITS (SEQUENCES AND/OR PLASMIDS) WILL BE PROVIDED TO ARMY RESEARCHERS AND OTHERS UPON REQUEST. KK1956-19 Parent award context Parent award agency: Department of Defense · Department of the Army Parent award NAICS: 541715 Parent award performance state: CA Parent award description: TASK ORDER 00019 (74393 LS-ICB) View parent award on USAspending | W911NF19D0001USAspending | $600,000 | Dec 10, 2021 | — – — |
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Agencies supported
- National Aeronautics and Space AdministrationGov-sourced
- Department of DefenseGov-sourced
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