Battelle Memorial Institute

NATIONAL ECOLOGICAL OBSERVATORY NETWORK: OPERATIONS ACTIVITIES

NEON OPERATIONS AND MAINTENANCE: EVOLVING FROM A STRONG FOUNDATION -THE FUTURE HEALTH, WELFARE, AND SECURITY OF THE U.S. DEPEND UPON DIVERSE NATURAL SYSTEMS THAT CAN BE ALTERED BY THE CHANGING WORLD. THE NATIONAL ECOLOGICAL OBSERVATORY NETWORK (NEON), THE FIRST CONTINENTAL-SCALE FACILITY OF ITS KIND IN THE WORLD, ADDRESSES THE NATURE OF THESE CHANGES AND THEIR CAUSES BY ACQUIRING STANDARDIZED BIOLOGICAL AND ENVIRONMENTAL MEASUREMENTS FROM THE LOCAL TO CONTINENTAL SCALE. IT PROVIDES KEY DATA TO ENABLE SCIENTISTS TO UNDERSTAND AND PREDICT THE CHANGES AND ENABLE POLICY MAKERS POTENTIALLY TO LESSEN DETRIMENTAL EFFECTS. NEON IS DEMOCRATIZING ACCESS TO THIS AREA OF SCIENCE IN UNPRECEDENTED WAYS BY PROVIDING HIGH-QUALITY DATA FREE OF CHARGE TO ANYONE INTERESTED IN PURSUING ADVANCED ECOLOGICAL AND CLIMATE RESEARCH. NEON PROVIDES OUTREACH NATIONWIDE IN EACH OF ITS 20 ECOLOGICAL REGIONS TO BUILD A DIVERSE, INCLUSIVE, AND INTERDISCIPLINARY NEXT GENERATION OF RESEARCHERS. WITH ITS PARTNERS, NEON PROVIDES DATA SKILLS TRAINING AND EDUCATIONAL MATERIALS TO A WIDE VARIETY OF STAKEHOLDERS. THE NEON MISSION IS TO ENABLE BETTER UNDERSTANDING AND PREDICTION OF THE DRIVERS OF, AND RESPONSES TO, ECOLOGICAL CHANGES BY PROVIDING FREELY AVAILABLE, HIGH-QUALITY CONTINENTAL AND DECADAL-SCALE ECOLOGICAL DATA AND SAMPLES INFORMED BY BROAD SCIENTIFIC ENGAGEMENT. THE MANAGING ENTITY FOR THIS PROJECT REALIZES THIS MISSION AND ADVANCES THE POTENTIAL FOR DISCOVERY BY PROVIDING RAPID AND BROADENED ACCESS TO HIGH-QUALITY NEON DATA AND SAMPLES THROUGH ROBUST, SECURE, AND ACCESSIBLE CYBERINFRASTRUCTURE, EDUCATIONAL AND OUTREACH PROGRAMS, FINDABLE, ACCESSIBLE, INTEROPERABLE, AND REUSABLE ? FAIR - DATA PARTNERS, AND THE NEON BIOREPOSITORY. THE ROBUST NEON CYBERINFRASTRUCTURE THAT PROVIDES FREE AND OPEN ACCESS TO DATA AND ANALYTIC TOOLS WILL CONTINUE TO EMPOWER A COMMUNITY OF PRACTICE TO DEVELOP OPEN-SOURCE CODE, ANALYTIC TOOLS, STANDARDIZED PROTOCOLS, AND DERIVED ECOLOGICAL DATA PRODUCTS. NEON INFRASTRUCTURE IS CONTINUOUSLY OPERATED AT 81 SITES IN 20 DISTINCT ECOLOGICAL REGIONS SPANNING THE CONTINENTAL UNITED STATES, ALASKA, HAWAII, AND PUERTO RICO. OVER 180 DATA PRODUCTS ARE COLLECTED USING A SENSOR NETWORK, AIRBORNE REMOTE SENSING, AND MANUAL FIELD OBSERVATIONS AND COLLECTIONS. THESE FREE AND OPENLY AVAILABLE DATA ARE PROVIDED TO SCIENTISTS, EDUCATORS, AND THE PUBLIC FOR SOCIETAL BENEFIT THROUGH THE NEON DATA PORTAL (HTTPS://DATA.NEONSCIENCE.ORG/). PHYSICAL SAMPLES ARE COLLECTED AND MADE AVAILABLE FOR USE THROUGH THE NEON BIOREPOSITORY (HTTPS://BIOREPO.NEONSCIENCE.ORG/PORTAL/). NEON PROVIDES CUSTOMIZED ACCESS TO MANY PARTS OF ITS INFRASTRUCTURE, INCLUDING PERSONNEL, THROUGH A COST-RECOVERABLE ASSIGNABLE ASSETS PROGRAM. CENTRALIZED PLANNING DRIVES EFFICIENT MANAGEMENT WITH CONSISTENCY AND QUALITY IN DATA; DECENTRALIZED EXECUTION ACROSS THE 20 NEON DOMAINS ACCOMMODATES THE DIVERSITY OF ENVIRONMENTS IN THE US. THE POTENTIAL FOR NEON TO ADVANCE INTERDISCIPLINARY KNOWLEDGE WILL BE AMPLIFIED BY ENGAGING IN EXTENSIVE STRATEGIC PARTNERSHIPS. NEON WILL BUILD A DIVERSE, INCLUSIVE, AND INTERDISCIPLINARY NEXT GENERATION OF RESEARCHERS AND WORKFORCE BY PROVIDING TRAINING IN THE USE OF NEON DATA, SUPPORTING NEON AMBASSADORS AND PARTNERS, AND CONDUCTING TRAINING IN STANDARDIZED ECOLOGICAL FIELD SAMPLING PROTOCOLS. CONTINUAL IMPROVEMENT OF NEON OPERATIONS, INCLUDING TRAINING AND OUTREACH ACTIVITIES, WILL BE DRIVEN BY REGULAR EXTERNAL EVALUATION AGAINST OBSERVATORY PERFORMANCE METRICS. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE PLANNED FOR THIS AWARD.

INCREMENTAL FUNDING, MAKE IN-SCOPE REVISIONS, REPLACES THE COGNIZANT ADMIN OFFICE, MINOR CHANGES

NATIONAL ECOLOGICAL OBSERVATORY NETWORK: CONSTRUCTION AND TRANSITION

NATIONAL ECOLOGICAL OBSERVATORY NETWORK: OPERATIONS ACTIVITIES

TAS::89 0328::TAS RECOVERY - BATTELLE MEMORIAL INSTITUTE - PACIFIC NORTHWEST DIVISION SMART GRID DEMONSTRATION PROJECT

MIDWEST CARBON SEQUESTRATION REGIONAL PARTNERSHIP - PHASES II AND III

FUNDING OPPORTUNITY ANNOUNCEMENT NO BIL-DE-FOA-0002735, AWARD NO. DE-CD00000021, DIRECT AIR CAPTURE, BATTELLE MEMORIAL INSTITUTE

MRCSP-PHAE II

PURPOSE: BATTELLE WILL SUPPORT THE INNOVATION FUNDS OBJECTIVES BY DELIVERING AN INTEROPERABLE OPEN RAN RADIO UNIT (O-RU) THAT PROVIDES IMPROVED PERFORMANCE THROUGH ITS PATENTED APERTURE DESIGN WHILE IT SIGNIFICANTLY REDUCES TOTAL COST OF OWNERSHIP (TCO) THROUGH EQUIPMENT CONSOLIDATION. ACTIVITIES TO BE PERFORMED: THE INVESTMENT WILL SUPPORT COMPREHENSIVE INTEROPERABILITY TESTING WITH DISTRIBUTED UNITS (DUS) FROM MULTIPLE VENDORS TO ENSURE SEAMLESS INTEGRATION INTO THE O-RAN ECOSYSTEM, AND WILL ADDRESS CRITICAL CHALLENGES SUCH AS CAPACITY DEMANDS, SMALL FORM FACTOR REQUIREMENTS, ENERGY EFFICIENCY, 3RD GENERATION PARTNERSHIP PROJECT (3GPP) COMPLIANCE, AND SECURITY CONFORMANCE. EXPECTED OUTCOMES: THE END RESULT OF THIS GRANT WILL PRODUCE A SPIN-OUT COMPANY THAT LEVERAGES THIS FOOTHOLD IN THE MARKET TO EXPAND AND SUPPORT A COMPLETE O-RU PRODUCT LINE, MIRRORING THE APPROACH WITH BATTELLE'S PREVIOUS MULTIBILLION-DOLLAR TELECOM SPINOUT, PHOTON INTEGRATION RESEARCH INC. (PIRI). THE PROPOSED BATTELLE O-RU BRINGS SUBSTANTIAL COST SAVINGS AND NEW CAPABILITIES TO DOMESTIC AND INTERNATIONAL WIRELESS MNOS, NEUTRAL HOST PROVIDERS, AND PRIVATE NETWORK OPERATORS BY SUPPORTING A WIDE BANDWIDTH NOT ACCOMMODATED BY EXISTING FR1 RUS AND ANTENNAS. THE CUTTING-EDGE FR1 BROADBAND MASSIVE MULTIPLE INPUT-MULTIPLE OUTPUT (MIMO) CAPABLE RU, WHICH INCORPORATES A UNIQUE APERTURE DESIGN COMBINED WITH ADVANCED RF FRONT-END AND DIGITAL SIGNAL PROCESSING, ALLOWS OPERATORS TO UTILIZE SPECTRUM BETWEEN 600 MHZ AND 7 GHZ EFFICIENTLY IN A SINGLE UNIT, MATCHING THE OUTPUT POWER OF EXISTING DISCRETE NARROWBAND RUS. INTENDED BENEFICIARIES: BATTELLE O-RU WILL EXPEDITE THE INTRODUCTION OF A MARKET LEADING, ENERGY-EFFICIENT RU AND WILL ALSO DIMINISH INFRASTRUCTURE COSTS FOR MOBILE NETWORK OPERATIONS (MNOS), NEUTRAL HOSTS, AND PRIVATE NETWORK PROVIDERS, THEREBY PROMOTING A MORE CONNECTED AND EFFICIENT TECHNOLOGICAL FUTURE. SUBRECIPIENT ACTIVITIES: THE RECIPIENT DOES NOT PLAN TO SUBAWARD FUNDS.

THE APPALACHIAN REGIONAL CLEAN HYDROGEN HUB (ARCH2) WILL DEVELOP TEN HYDROGEN PRODUCTION FACILITIES, ONE HYDROGEN STORAGE FACILITY WITH CONNECTED PIPELINES, AND OFFTAKE CAPABILITY FOR MULTIPLE HYDROGEN END-USERS. HYDROGEN WILL BE PRODUCED USING AUTO-THERMAL REFORMING (ATR) WITH CARBON CAPTURE, SEQUESTRATION, AND STORAGE (CCS), ELECTROLYSIS, BIOMASS PYROLYSIS, AND SEPARATION FROM WASTE GASES. HYDROGEN WILL BE USED IN A VARIETY OF SECTORS, INCLUDING PROJECTS IN RESIDENTIAL FUEL CELLS, QUARRY VEHICLES, DATA CENTERS, AGRICULTURE, INDUSTRIAL HEAT, AND MOBILITY. HYDROGEN PRODUCTION AND USE WILL BE A COMBINATION OF ON-SITE OR NEAR-SITE PRODUCTION/STORAGE/USE AND CONNECTED VIA A PIPELINE SYSTEM AND HYDROGEN STORAGE IN BEDDED SALT FORMATIONS.

A PROTEOMICS RESEARCH CENTER FOR INTEGRATIVE BIOLOGY

PROMOTR: A PROTEOMICS CENTER FOR MOTRPAC

CENTER FOR APPLICATION OF ADVANCED CLINICAL PROTEOMIC TECHNOLOGIES FOR CANCER

NEW AWARD DE-FE0031836 WITH BATTELLE MEMORIAL INSTITUTE TITLED REGIONAL INITIATIVE TO ACCELERATE CCUS DEPLOYMENT IN THE MIDWESTERN AND NORTHEASTERN USA

A PROTEOMICS RESEARCH RESOURCE FOR INTEGRATIVE BIOLOGY

PURPOSE: GRID ENABLED CYBER OPERATIONS RANGE (GECO) WILL CREATE A GRID CYBER TEST RANGE ON SAVANNAH RIVER NATIONAL LAB?S EXISTING MEDIUM VOLTAGE TESTBED FACILITY, INFORMED BY THE PRIVATE SECTOR. THIS PROJECT CONVENES A COMBINATION OF STAKEHOLDERS: A NATIONAL LAB, UTILITIES, PRIVATE SECTOR PARTNERS, AND NATIONAL CYBER DEFENSE AUTHORITIES. ACTIVITIES TO BE PERFORMED: 1. ACQUIRE THREE MODULAR AND MOBILE OPERATIONS TESTING CENTERS THAT WILL UTILIZE A PRIMARY TEST NETWORK AND A SAFETY OVERSIGHT NETWORK. THESE NETWORKS WILL INCLUDE CRITICAL ENERGY GENERATION AND STORAGE TECHNOLOGIES SUCH AS PHOTOVOLTAICS, BATTERY ENERGY STORAGE, VIRTUALIZED LOADS, AND COMMAND AND CONTROL ALGORITHMS. 2. CONDUCT CYBER EXERCISES IN THE THREE OPERATIONS TESTING CENTERS, FOCUSING ON PENETRATION TESTING AND ATTACKS; SUPERVISORY OBSERVATION, SAFETY OVERSIGHT TOOLS AND PROTOCOL; AND VULNERABILITY MITIGATION AND DEFENSIVE CYBER OPERATIONS TRAINING. 3. PROVIDE GRID-SPECIFIC RISK ASSESSMENTS OF THE SUPPLY CHAIN FOR COMPONENTS DOWN TO POINT OF ORIGIN, ENSURING FOREIGN ADVERSARIES ARE NOT UNDULY INFLUENCING U.S. GRID EQUIPMENT. TRAIN GRID CYBER OPERATORS AND/OR STUDENTS IN COLLABORATION WITH UTILITIES, EDUCATIONAL INSTITUTIONS, AND DEFENSE LEADERS. PROVIDE SUPPLY CHAIN RISK MANAGEMENT TRAINING TO PRIVATE SECTOR GRID OPERATORS AND EQUIPMENT MANUFACTURERS. EXPECTED OUTCOMES: GECO?S WORKFORCE EFFORT WILL ADDRESS THE REGION?S SHORTAGE IN CYBER PROFESSIONALS BY PROVIDING TRAINING OPPORTUNITIES TO 120 CYBER DEFENDERS BY OCTOBER 2026. GECO WILL SPUR ECONOMIC GROWTH BY PROVIDING OPPORTUNITIES FOR ENTERPRISES AND LOCAL SUPPLY CHAINS TO PROVIDE THE REQUIRED MATERIALS AND SERVICES FOR THE EMERGING DISTRIBUTED ENERGY RESOURCES ECONOMY. GECO WILL HELP COMMERCIALIZE PREVIOUSLY OVERLOOKED TECHNOLOGIES THAT ARE RIPE FOR MARKET DISRUPTION BY LINKING PRIVATE SECTOR PLAYERS WITH DEFENSE AND PUBLIC SECTOR EXPERTISE. GECO WILL MAKE SC NEXUS MORE ATTRACTIVE FOR LARGE-SCALE INVESTMENT IN ENERGY, CYBER, AND DEFENSE INDUSTRIES. OVER TIME, THE PROPOSED PROGRAMMING WILL GENERATE 1,200 DIRECT JOBS AND $1.7B IN TOTAL OUTPUT OVER THE LIFE OF THE INVESTMENT.

3D IMAGING & COMPUTER MODEL OF THE RESPIRATORY TRACT

NEW AWARD DE-FE0031623 TITLED ''INTEGRATED MIDCONTINENT STACKED CARBON STORAGE HUB''

BIPARTISAN INFRASTRUCTURE LAW (BIL): CARBON STORAGE COMPLEX FEASIBILITY IN PARADISE, KENTUCKY – CARBONSAFE PHASE II THE PROJECT’S PRIMARY GOAL IS TO EVALUATE THE FEASIBILITY OF A COMMERCIAL-SCALE CARBON CAPTURE AND STORAGE (CCS) PROJECT IN PARADISE, MUHLENBERG COUNTY, KENTUCKY, AT THE TENNESSEE VALLEY AUTHORITY (TVA) PARADISE POWER PLANT.

CARBON STORAGE COMPLEX FEASIBILITY FOR COMMERCIAL DEVELOPMENT IN SOUTHEASTERN MICHIGAN THE PROJECT WILL PROVIDE A FEASIBILITY ASSESSMENT OF THE TECHNICAL AND NON-TECHNICAL ASPECTS OF AN INTEGRATED CARBON STORAGE PROJECT IN THE SOUTHEASTERN MICHIGAN BASIN REGION. THE OVERALL OBJECTIVE OF THE PROJECT IS TO ADVANCE COMMERCIALITY OF CARBON CAPTURE AND STORAGE (CCS) IN THE SOUTHEASTERN MICHIGAN BASIN WHILE SUPPORTING, PROMOTING, AND PROTECTING DIVERSITY, EQUITY, INCLUSION, AND ACCESSIBILITY (DEIA); DISADVANTAGED COMMUNITIES; AND ENVIRONMENTAL JUSTICE (EJ) COMMUNITIES.

DE-FE0031792; BATTELLE MEMORIAL INSTITUTE,''CHEMICALLY ENABLED CARBON DIOXIDE ENHANCED OIL RECOVERY IN MULTI-POROSITY, HYDROTHERMALLY ALTERED CARBONATES IN THE SOUTHERN MICHIGAN BASIN''

SOLID STATE NMR STRUCTURE/FUNCTION STUDIES OF AMELOGENIN

PROTEOGENOMIC TRANSLATIONAL RESEARCH CENTER FOR CLINICAL PROTEOMIC

CENTER FOR ADVANCED MULTI-OMIC CHARACTERIZATION OF CANCER - PROJECT SUMMARY THE OVERALL OBJECTIVE OF THE PNNL PROTEOME CHARACTERIZATION CENTER (PCC) IS TO COMPREHENSIVELY CHARACTERIZE HUMAN TUMOR SAMPLES PROVIDED BY THE NATIONAL CANCER INSTITUTE (NCI), AND TO INTEGRATE THE MULTI-OMIC MEASUREMENTS TO SUPPORT IMPROVED UNDERSTANDING OF THE MOLECULAR CHANGES THAT CHARACTERIZE CANCER, AND DO SO IN THE CONTEXT OF CLINICAL OUTCOME. PNNL HAS PARTICIPATED IN THE NCI’S CLINICAL PROTEOMIC TUMOR ANALYSIS CONSORTIUM (CPTAC) AS A PCC FOR THE PAST TEN YEARS, WITH RESPONSIBILITY FOR COMPREHENSIVE PROTEOGENOMIC CHARACTERIZATION OF HIGH-GRADE SEROUS OVARIAN, COLON, AND ENDOMETRIAL CANCERS, AND GLIOBLASTOMA. THE PLANNED PNNL PCC WILL BUILD ON THOSE ACHIEVEMENTS TO EXTEND AND ADVANCE THE CPTAC MISSION OF COMPREHENSIVE PROTEOGENOMIC CHARACTERIZATION OF HUMAN CANCERS TO ADDITIONAL CANCER TYPES, MEETING OR EXCEEDING CPTAC KEY EXPECTATIONS OR REQUIREMENTS FOR SAMPLE THROUGHPUT, COVERAGE, SAMPLE SIZE, AND DATA QUALITY. UTILIZING AN ADVANCED ANALYTICAL PLATFORM, PNNL PLANS TO ADD ANALYSIS OF BOTH ACETYLOME AND UBIQUITINOME TO THE PHOSPHOPROTEOME OF PROSPECTIVELY COLLECTED HUMAN TUMORS, TO BETTERS ILLUMINATE KEY BIOCHEMICAL PROCESSES RELATED TO PROTEIN-PROTEIN INTERACTIONS, PROTEIN DEGRADATION, AND SIGNAL TRANSDUCTION. WE WILL ALSO COMPLEMENT THE CORE PROTEOME AND POST-TRANSLATIONAL MODIFICATION (PTM)-OME ANALYSIS WITH GLOBAL METABOLOME AND LIPIDOME ANALYSIS, AS WELL AS SELECTED DATA DRIVEN SPATIAL OR SINGLE-CELL PROTEOMICS ANALYSIS. THIS WILL PROVIDE ADDITIONAL CRITICAL INSIGHTS ON POTENTIAL METABOLIC VULNERABILITIES AND TUMOR HETEROGENEITY AS WELL AS MICROENVIRONMENT CONTRIBUTIONS. THIS MULTI-OMIC ANALYSIS STRATEGY WILL ALSO BE APPLIED TO PRECLINICAL SAMPLES, SUCH AS CELL LINES, ORGANOIDS AND PATIENT-DERIVED XENOGRAFTS. WE WILL ALSO DEVELOP TARGETED MASS SPECTROMETRIC ASSAYS USING INPUT FROM THE CPTAC CONSORTIUM, AND PARTICULARLY THE PROTEOGENOMIC DATA ANALYSIS CENTERS (PGDACS), TO PRIORITIZE TARGETS FOR FURTHER EXPLORING IMPORTANT MECHANISTIC PROTEOMIC CHANGES IN INDEPENDENT COHORT(S). THROUGHOUT THIS WORK OUR MEASUREMENTS WILL BENEFIT FROM FURTHER PERFORMANCE INCREASES (E.G., SENSITIVITY AND THROUGHPUT) BASED ON REFINING, VALIDATING AND IMPLEMENTING DEVELOPMENTS FROM BOTH PNNL AND THE OTHER CPTAC CENTERS. THE PNNL PCC WILL IDENTIFY PROMISING CANCER SIGNATURES AND SIGNALING NETWORKS THROUGH PROTEOMIC AND METABOLOMIC ANALYSIS OF HUMAN BIOSPECIMENS AND RELEVANT PRECLINICAL SAMPLES FOR 2-3 CANCER TYPES SELECTED BY THE CPTAC, USING STATE-OF-THE-ART LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY INSTRUMENTATION, HIGHLY MULTIPLEXED ISOBARIC MASS-TAG LABELING (TMT 16-PLEX), AND INTEGRATED SAMPLE WORKFLOWS, AS WELL AS ADDITIONAL ADVANCED METABOLOMIC, SPATIAL AND SINGLE-CELL PROTEOMIC PLANFORMS, AT A THROUGHPUT OF 300 SAMPLES PER YEAR. WE WILL ALSO EXPLORE MECHANISTICALLY IMPORTANT PROTEOMIC CHANGES IN HUMAN SPECIMENS AND MODEL SYSTEMS USING CUTTING-EDGE TARGETED PROTEOMIC PLATFORMS, ANALYTICALLY VALIDATED AND HIGHLY MULTIPLEXED TARGETED ASSAYS, AND WORKFLOWS MEETING THE CPTAC TIER 2 ASSAY GUIDELINES. TWO HUNDRED HIGHLY SPECIFIC, MULTIPLEXED TARGETED PROTEOMICS ASSAYS WILL BE DEVELOPED AND USED FOR MEASUREMENTS IN 300 SAMPLES EACH YEAR. THE PNNL PCC WILL ACCOMPLISH BOTH UNBIASED AND TARGETED MULTI-OMIC CHARACTERIZATION OF CANCERS IN CONJUNCTION WITH IMPROVING THE DEPTH, THROUGHPUT AND QUALITY OF BOTH UNBIASED AND TARGETED DATA GENERATED BY IMPLEMENTING AND DEPLOYING RELEVANT NEW TECHNOLOGIES, SUCH AS NANOSCALE PTM, METABOLOMIC ANALYSIS, AND SINGLE-CELL PROTEOMICS ANALYSIS. THE PNNL PCC WILL WORK CLOSELY WITH THE OTHER PCCS, PGDACS AND PTRCS IN THE CPTAC NETWORK ON DATA INTEGRATION AND BIOINFORMATICS ANALYSIS, AS WELL AS TRANSLATIONAL APPLICATIONS.

INTEGRATING STRUCTIVE ACTIVITY, BIOKINETICS AND RESPONSE FOR ENP RISK ASSESSMENT

PNNL PROTEOME CHARACTERIZATION CENTER

CONSORTIA FOR HIGH-THROUGHPUT-ENABLED STRUCTURAL BIOLOGY PARTNERSHIPS (U01)

PSP OMICS CENTER OF ACUTE TO CHRONIC PAIN SIGNATURES

APBS: NANOSCALE BIOMOLECULAR ELECTROSTATICS SOFTWARE

MULTI-OMIC 3D TISSUE MAPS FOR A HUMAN BIOMOLECULAR ATLAS

THE OVERALL OBJECTIVE OF THIS COOPERATIVE AGREEMENT IS TO ASSIST INSTITUTIONS IN STRENGTHENING THEIR LEGAL, TECHNICAL, RESEARCH, ANALYTICAL, PROGRAM

RESEARCH CENTER FOR SPATIOTEMPORAL LUNG IMAGING AND OMICS

PACIFIC NORTHWEST ADVANCED COMPOUND IDENTIFICATION CORE

PIPELINE SAFETY PROGRAM BASE G

CENTER FOR LUNG DEVELOPMENT IMAGING AND OMICS

CENTER FOR NOVEL BIOMARKERS OF RESPONSE

TAS::89 0321::TAS UPGRADING OF INTERMEDIATE BIO-OIL PRODUCED BY CATALYTIC PYROLYSIS

NP-MRD: NATURAL PRODUCTS MAGNETIC RESONANCE DATABASE

ROBUST MASS SPECTROMETRIC PROTEIN/PEPTIDE ASSAYS FOR TYPE 1 DIABETES CLINICAL APPLICATIONS - PROJECT SUMMARY/ABSTRACT: TYPE 1 DIABETES (T1D) IS A DEVASTATING DISEASE OFTEN OCCURRING IN CHILDREN AND YOUNG ADULTS RESULTING FROM THE AUTOIMMUNE-MEDIATED LOSS OF PANCREATIC SS-CELLS. IT HAS BEEN CHALLENGING FOR MONITORING THE DISEASE PROGRESSION AND THE EFFICACY OF CLINICAL INTERVENTIONS. THEREFORE, A CRITICAL NEED REMAINS FOR HIGHLY RELIABLE ASSAYS THAT QUANTIFY PROTEINS OR PEPTIDE HORMONES (E.G., INSULIN, GLUCAGON) AND THEIR SPECIFIC ISOFORMS (OR PROTEOFORMS) AS MARKERS OF ENDOCRINE AND EXOCRINE FUNCTION. SUCH ASSAYS WILL PLAY AN IMPORTANT ROLE IN FACILITATING EFFECTIVE MONITORING OF DISEASE PROGRESSION OR EFFICACY OF NOVEL CLINICAL INTERVENTIONS PRIOR TO OR FOLLOWING THE ONSET OF T1D. MOST CURRENT CLINICAL ASSAYS DEPEND ON THE USE OF ANTIBODIES OR OTHER AFFINITY REAGENTS ALMOST EXCLUSIVELY. HOWEVER, THE EXACT SPECIFICITY OF AFFINITY REAGENTS IS OFTEN UNKNOWN OR DIFFICULT TO CHARACTERIZE. TARGETED MASS SPECTROMETRY (MS) PRESENTS A PROMISING ALTERNATIVE TO IMMUNOASSAYS. THEREFORE, THE OVERALL OBJECTIVE OF THIS APPLICATION IS TO DEVELOP RELIABLE, PROTEOFORM-SPECIFIC, AND MULTIPLEX TARGETED MS ASSAYS FOR A LIST OF PROTEIN/PEPTIDE ANALYTES OF SIGNIFICANCE IN T1D. SPECIFICALLY, WE AIM TO DEVELOP MULTIPLEX TARGETED MS ASSAYS FOR THE FOLLOWING PANEL OF TARGETS AS MARKERS OF ENDOCRINE AND EXOCRINE FUNCTION: INSULIN, GLUCAGON, AMYLIN, CHROMOGRANIN, SOMATOSTATIN, PROHORMONE ISOFORMS (E.G., PROINSULIN, PROGLUCAGON), HYBRID INSULIN PEPTIDES, TRYPSINOGEN, GLYCATED CD59, AS WELL AS OTHER MARKERS OF INTEREST TO THE T1D RESEARCH COMMUNITY. TO FACILITATE FULL VALIDATION OF THE ROBUSTNESS AND TRANSFERABILITY OF THE ASSAYS, THE OVERALL OBJECTIVE WILL BE ACCOMPLISHED THROUGH THE COLLABORATIVE EFFORTS OF TWO INDEPENDENT TARGETED MS LABS AND THROUGH A MULTI-LAB ASSAY VALIDATION EFFORT. SPECIFICALLY, AIM 1 WILL BE FOCUSED ON ESTABLISHING OPTIMAL ASSAY CONFIGURATIONS FOR CONFIDENT DETECTION OF ENDOGENOUS ANALYTES IN SERUM SAMPLES FOR SPECIFIC PROTEOFORMS OR PEPTIDES OF INTEREST IN T1D. AIM 2 WILL BE CENTERED ON ASSAY OPTIMIZATION AND FULL ASSAY CHARACTERIZATION IN THE ASPECTS OF REPRODUCIBILITY, STABILITY, SELECTIVITY, LINEARITY, AND LIMIT OF QUANTIFICATION. INTER-LAB ASSAY PROTOCOL TRANSFER AND ASSAY CHARACTERIZATION WILL ALSO BE PURSUED. AIM 3 WILL DEMONSTRATE THE ROBUSTNESS AND UTILITY OF THE ASSAYS THROUGH MULTI-LAB VALIDATION OF THE ASSAYS BY ANALYZING THE SAME COHORT OF CLINICAL SERUM SAMPLES AND BENCHMARKING AGAINST WELL-ESTABLISHED IMMUNOASSAYS FOR SELECTED ANALYTES SUCH AS INSULIN AND C-PEPTIDE. TOGETHER, THE PROJECT WILL ESTABLISH HIGHLY RELIABLE AND EASY-TO-TRANSFER MULTIPLEX TARGETED MS ASSAYS FOR MANY DIFFICULT TO MEASURE T1D MARKERS. THESE ASSAYS ARE EXPECTED TO MAKE A SIGNIFICANT CONTRIBUTION TO THE MONITORING OF PANCREATIC ENDOCRINE/EXOCRINE FUNCTIONS, THE DISEASE PROGRESSION, AS WELL AS THE EFFICACY OF CLINICAL INTERVENTIONS IN T1D RESEARCH.

MID-ATLANTIC U.S. OFFSHORE CARBON STORAGE RESOURCE ASSESSMENT PROJECT

A SCALABLE MASS SPECTROMETRY PLATFORM FOR PROTEOME MAPPING OF BRAIN TISSUES - ABSTRACT THE BRAIN IS THE MOST COMPLEX ORGAN IN THE MAMMALIAN BODY. BULK ANALYSIS OBSCURES HETEROGENEITY OF CELL TYPES PRESENT EVEN IN THE SMALLEST BRAIN REGIONS. MULTI-OMICS SINGLE-CELL RESOLUTION 3D-CHARACTERIZATION OF BRAIN TISSUE IS CRITICALLY IMPORTANT TO CREATE COMPREHENSIVE BRAIN CELL CENSUSES AND ALTAS. RECENT TECHNOLOGICAL ADVANCES ALLOW FOR SINGLE-CELL TRANSCRIPTOME MAPPING OF MAMMALIAN BRAINS, BUT SINGLE-CELL PROTEOMICS TECHNOLOGIES ARE LAGGING FAR BEHIND TRANSCRIPTOMICS TECHNOLOGIES. THE LACK OF HIGH-RESOLUTION PROTEOME CHARACTERIZATION OF BRAIN TISSUES IN THE BICCN CONSORTIUM REPRESENTS A SIGNIFICANT KNOWLEDGE GAP BETWEEN PROTEIN AND MRNA FOR ACHIEVING A MORE COMPLETE UNDERSTANDING OF HOW DIVERSE BRAIN CELLS ARE ORGANIZED INTO DISTINCT ANATOMICAL AND FUNCTIONAL REGIONS. THE OBJECTIVE OF THIS APPLICATION IS TO ADDRESS THIS GAP BY DEVELOPING A ROBUST SCALABLE MASS SPECTROMETRY (MS) PLATFORM FOR HIGH-RESOLUTION 3D-PROTEOME MAPPING OF BRAIN TISSUES. THE FEASIBILITY IS STRONGLY SUPPORTED BY OUR RECENT PROGRESS IN TECHNOLOGY DEVELOPMENT AND OUR EXPERIENCES IN PROTEOME MAPPING OF MOUSE TISSUES. AIM 1 WILL FOCUS ON THE DEVELOPMENT OF A ROBUST SCALABLE MS PLATFORM THROUGH 1) FURTHER IMPROVING SAMPLE PREPARATION FOR RAPID EFFECTIVE PROCESSING OF SINGLE CELLS AND SMALL TISSUE VOXELS, AND 2) LEVERAGING MULTIPLE DISRUPTIVE TECHNOLOGIES DEVELOPED AT OUR GROUP FOR SIGNIFICANTLY IMPROVING DETECTION SENSITIVITY AND SAMPLE THROUGHPUT. THE NEW PLATFORM IS EXPECTED TO ALLOW FOR RELIABLE QUANTIFICATION OF >3,000 PROTEINS IN SINGLE CELLS AND >6500 PROTEINS IN 100 CELLS WITH ~500 SAMPLES PER DAY. AIM 2 WILL OPTIMIZE AND DEMONSTRATE THE SCALABLE MS PLATFORM FOR 2D-PROTEOME MAPPING OF MOUSE MOP AND HUMAN M1 WHEN COMBINED WITH LASER CAPTURE MICRODISSECTION FOR TISSUE VOXELS. AIM 3 WILL APPLY THE NEW PLATFORM FOR 3D-PROTEOME MAPPING OF MOP/M1 WITHIN THE BICCN CONSORTIUM AND INTEGRATE PROTEOMIC DATA WITH EXISTING TRANSCRIPTOMIC DATA FOR PROTEOGENOMIC ANALYSIS. WE ENVISION THAT THE NEW PLATFORM WILL BECOME A CONVENIENT INDISPENSABLE TOOL FOR HIGH-RESOLUTION 3D-PROTEOME MAPPING OF BRAIN TISSUES IN THE BICCN CONSORTIUM AND EXTEND THE BICCN TOOLBOX. IN TURN, IT COULD MAKE SUBSTANTIAL CONTRIBUTIONS TO IMPROVE OUR UNDERSTANDING OF BRAIN FUNCTION IN HEALTH AND DISEASE.

MULTIPLEX MASS SPECTROMETRIC PROTEIN ASSAYS FOR PRECISE MONITORING OF THE PATHOPHYSIOLOGY OF OBESITY

NEW AWARD TO THE BATELLE MEMORIAL INSTITUTE. PROJECT ENTITLED: CO2 BINDING ORGANIC LIQUIDS GAS CAPTURE WITH POLARITY SWING ASSISTED REGENERATION.

NEW AWARD--ECONOMIC ANALYSIS OF POLYMER ELECTROLYTE MEMBRANE (PEM) FUEL CELL SYSTEMS

NON-INVASIVE BIOMONITORING OF PESTICIDES

DISCOVERY OF PATHWAYS AND MOLECULAR MEDIATORS OF EARLY T1D PATHOGENESIS USING SPATIAL MULTI-OMICS - PROJECT SUMMARY/ABSTRACT TYPE 1 DIABETES (T1D) IS A COMPLEX, DEVASTATING AUTOIMMUNE DISEASE WITH A SLOW PROGRESSION OF PANCREATIC BETA-CELL DYSFUNCTION (E.G., A DECLINE OF FIRST PHASE INSULIN RELEASE OCCURS OVER SEVERAL YEARS) BEFORE THE CLINICAL ONSET OF T1D. UNFORTUNATELY, WE STILL HAVE A LACK OF KNOWLEDGE ON THE MOLECULAR MECHANISMS OF EARLY T1D PATHOGENESIS. THE LONG-TERM GOAL OF THIS PROJECT IS TO GAIN A DETAILED UNDERSTANDING OF IN SITU MOLECULAR MECHANISMS OF EARLY HUMAN T1D DEVELOPMENT THROUGH ADVANCED SPATIAL OMICS PROFILING OF HUMAN ISLET MICROENVIRONMENTS WITHIN CLINICAL TISSUE SPECIMENS AND FUNCTIONAL STUDIES OF NOVEL MEDIATORS. OUR RESEARCH PLAN CENTERS ON THE CRITICAL ROLE OF HUMAN ISLET MICROENVIRONMENTS IN DISEASE PROGRESSION AND THE OBSERVATIONS OF SUBSTANTIAL INTRA-DONOR HETEROGENEITY OF ISLET MICROENVIRONMENTS (IN BOTH PRE-DIABETIC AND RECENT-ONSET SUBJECTS) FOR UNRAVELING PROGRESSION INFORMATION. OUR HYPOTHESIS IS THAT PATHWAYS OR MOLECULAR MEDIATORS OF DISEASE PROGRESSION (OTHERWISE UNATTAINABLE WITHOUT LONGITUDINAL SAMPLES) CAN BE UNCOVERED THROUGH ADVANCED SPATIAL MULTI-OMICS PROFILING OF INDIVIDUAL ISLET MICROENVIRONMENTS IN THE CONTEXT OF INTRA-DONOR HETEROGENEITY FOR EACH PRE-T1D OR NEW-ONSET T1D DONOR. SPATIAL OMICS DATA ON INDIVIDUAL ISLET MICROENVIRONMENTS WILL UNRAVEL “PSEUDO- TIME” PROGRESSION OF ISLET DYSFUNCTION WITHIN EACH DONOR. COMMON PATHWAYS AND MOLECULAR MEDIATORS ACROSS MULTIPLE DONORS WILL BE IDENTIFIED FOR FUNCTIONAL STUDIES. OUR PLAN IS TO PURSUE SPATIAL MULTI-OMICS PROFILING OF ISLET MICROENVIRONMENTS AT TWO DIFFERENT RESOLUTIONS. AIM 1 WILL FOCUS ON CHARACTERIZING INTRA-DONOR HETEROGENEITY ACROSS INDIVIDUAL ISLET MICROENVIRONMENTS AT THE ROI (REGION OF INTEREST) LEVEL WITH EACH ISLET MICROENVIRONMENT AS A ROI. PSEUDO-TIME PROGRESSION AND ITS UNDERLYING PATHWAYS WILL BE UNCOVERED THROUGH CORRELATION ANALYSIS WITH PATHOLOGY SCORES FOR EACH ROI. ONE EXAMPLE OF THE PATHOLOGY SCORES IS THE IMMUNE SIGNATURE (A 20-PROTEIN PANEL DISCOVERED FROM OUR PRELIMINARY STUDIES) WHOSE EXPRESSION LEVELS CAN SERVE AS A PATHOLOGY SCORE FOR EACH ISLET MICROENVIRONMENT. AIM 2 WILL CHARACTERIZE ISLET MICROENVIRONMENTS AT THE SINGLE CELL RESOLUTION WITH THE GOAL TO REVEAL CELLULAR NICHES OF SPECIFIC TYPE OF ISLET DYSFUNCTION (E.G., INSULITIS OR Β-CELL LOSS). AIM 3 WILL EXPLORE THE FUNCTIONAL SIGNIFICANCE OF IDENTIFIED MOLECULAR MEDIATORS THROUGH ASSESSING THEIR ROLES IN CELLULAR COMMUNICATION AND BETA CELL SURVIVAL USING HUMAN ISLET/Β-CELLS AND ACINAR CELL CO-CULTURES. OUR APPROACH IS ENABLED BY MASS SPECTROMETRY-BASED SPATIAL PROTEOMICS, SPATIAL TRANSCRIPTOMICS, AND MASS SPECTROMETRY IMAGING (MSI) FOR LIPIDOMICS AND EXTRACELLULAR MATRIX (ECM)-OMICS. STATEMENT OF IMPACT: WE ANTICIPATE THIS PROJECT WILL ESTABLISH FIRST-OF-ITS-KIND SPATIAL MOLECULAR RESOURCES ON HUMAN ISLET MICROENVIRONMENTS IN EARLY STAGES OF T1D DEVELOPMENT, PROVIDE EVIDENCE OF NOVEL IN SITU MOLECULAR MEDIATORS AND BIOLOGICAL PROCESSES FROM HUMAN PATIENT SAMPLES, AND CONTRIBUTE TOWARDS THE DEVELOPMENT OF NOVEL THERAPEUTIC INTERVENTION STRATEGIES. THESE INNOVATIVE APPROACHES AND DATA RESOURCES WILL ALSO LIKELY ENHANCE THE OVERALL IMPACT OF THE CURRENT RESOURCES FROM THE HUMAN ISLET RESEARCH NETWORK (HIRN) AND ENABLE FURTHER COLLABORATIONS WITH OTHER INVESTIGATORS WITHIN THE T1D COMMUNITY.

REVERSE SENSITIVITY ANALYSIS FOR IDENTIFYING PREDICTIVE PROTEOMICS SIGNATURES OF CANCER

HIV PROTEOMIC CENTER FOR HOST-VIRAL RESPONSE CHARACTERIZATION

SIMULATION FRAMEWORK FOR REGIONAL GEOLOGIC CO2 STORAGE INFRASTRUCTURE ALONG ARCHES PROVINCE OF MIDWE

PATHWAYS AND CRITICAL REGULATORS OF EARLY BETA-CELL DYSFUNCTION IN TYPE 1 DIABETES

DESCRIPTION:EPA IS SOLICITING APPLICATIONS FROM QUALIFIED (NON-PROFIT) ENTITIES THAT HAVE AN INTEREST AND EXPERIENCE IN CONDUCTING ASSESSMENTS OR TESTS OF NEW OR EXISTING ENVIRONMENTAL MONITORING AND REMEDIATION TECHNOLOGIES FOR IDENTIFYING AND RECOVERING CRITICAL MINERALS (CMS) AT CONTAMINATED LEGACY MINING SITES. APPLICANTS MUST HAVE THE ABILITY AND KNOWLEDGE TO CONDUCT ASSESSMENT, TESTING AND QUALITY ASSURANCE SUPPORT FOR NEW (SBIR PHASE 2 AND 3) AND COMMERCIAL ENVIRONMENTAL MONITORING AND REMEDIATION TECHNOLOGIES. ABILITY AND KNOWLEDGE CAN BE ILLUSTRATED IN A NUMBER OF WAYS, INCLUDING BUT NOT LIMITED TO HAVING CONDUCTED THE SAME OR SIMILAR ACTIVITIES IN THE PAST AS THOSE DESCRIBED HERE. FAMILIARITY WITH FEDERAL COOPERATIVE AGREEMENT OR GRANT OPERATION AND MANAGEMENT WOULD ALSO BE HELPFUL FOR APPLICANTS TO HIGHLIGHT. DISPLAYING AND DESCRIBING PRODUCTIVITY UNDER THESE OR OTHER FEDERAL AGREEMENTS WOULD ALSO BENEFIT IN THE SOLICITATION PROCESS.ACTIVITIES:ACTIVITIES AND RESPONSIBILITIES OF THE RECIPIENT MUST INCLUDE: - ESTABLISHING A STAKEHOLDER GROUP AND TECHNICAL PANELS TO HELP IN PRIORITIZING TECHNICAL MONITORING AND RECOVERY NEEDS (I.E., CATEGORIES OF TECHNOLOGY TO ASSESS AND/OR TEST). - DEVELOPING AND SUBMITTING A SCIENTIFIC DATA MANAGEMENT PLAN (SDMP, SEE SECTION I.F. AND IV.D.6) AND A POST-AWARD INITIATIVE QUALITY MANAGEMENT PLAN (QMP) AND OPERATING THE INITIATIVE IN ACCORDANCE WITH THEIR QMP. - PROVIDING OUTREACH WORKSHOPS; - PREPARING AND DEVELOPING TECHNOLOGY TESTING PROTOCOLS THAT INCLUDE STAKEHOLDER NEEDS. - DEVELOPING PERFORMANCE METRICS FOR ASSESSING AND TESTING NEW OR EXISTING TECHNOLOGIES AS WELL AS SUSTAINABILITY METRICS FOR EVALUATING LONG TERM AND CROSS MEDIA IMPACTS OF THE CHARACTERIZATION OR RECOVERY TECHNOLOGIES. - POTENTIALLY MANAGING SUBAWARDS/CONTRACTS (AS NEEDED) WITH ORGANIZATIONS FOR MANAGING ASSESSMENT, TESTING AND DATA COLLECTION, AND WRITE PROGRESS AND SUMMARY REPORTS. RECIPIENT MAY CONDUCT (BUT ARE NOT LIMITED TO) CM IDENTIFICATION/MONITORING AND RECOVERY PROJECTS THAT PROVIDE: - OUTREACH ON THE INITIATIVE'S ACTIVITIES AND TRACK OUTCOMES FOR IMPACTS; - TECHNOLOGY AND PROCESS EVALUATIONS OR DEMONSTRATIONS; - TECHNICAL ASSISTANCE, OUTREACH AND/OR TRAINING TO MODEL OR ACCELERATE SOLUTIONS; - FEASIBILITY STUDIES; - EXPANDING ACCEPTANCE OF MONITORING OR RECLAMATION TECHNOLOGIES AT MINING SITES THROUGH TECHNOLOGY DEMONSTRATION PROJECTS OR TRAINING AND TECHNICAL ASSISTANCE; OR - DEMONSTRATION, TRAINING, OR TECHNICAL ASSISTANCE PROJECTS FOR DEVELOPING OR IMPROVING EXISTING TECHNOLOGIES FOR 'ALTERNATIVE USE.' - HELP MAKE TECHNOLOGY ASSESSMENTS MORE RELEVANT TO STAKEHOLDERS THROUGH SUCH ACTIVITIES AS ESTABLISHING RELATIONSHIPS WITH OTHER ORGANIZATIONS THAT CONDUCT TECHNOLOGY ASSESSMENT AND PERFORMANCE TESTING SIMILAR TO THAT UNDERTAKEN BY THE INITIATIVE. TECHNOLOGY DEMONSTRATIONS MUST INVOLVE NEW OR EXPERIMENTAL TECHNOLOGIES, METHODS, OR APPROACHES, WHERE THE RESULTS OF THE PROJECT WILL BE DISSEMINATED SO THAT OTHERS CAN BENEFIT FROM THE KNOWLEDGE GAINED IN THE DEMONSTRATION PROJECT. A PROJECT THAT IS ACCOMPLISHED THROUGH THE PERFORMANCE OF ROUTINE, TRADITIONAL, OR ESTABLISHED PRACTICES, OR A PROJECT THAT IS SIMPLY INTENDED TO CARRY OUT A TASK RATHER THAN TRANSFER INFORMATION OR ADVANCE THE STATE OF KNOWLEDGE, HOWEVER WORTHWHILE THE PROJECT MIGHT BE, IS NOT A DEMONSTRATION. THESE ACTIVITIES RELATE GENERALLY TO THE GATHERING OR TRANSFERRING OF INFORMATION OR ADVANCING THE STATE OF KNOWLEDGE. RECIPIENT SHOULD EMPHASIZE THIS 'LEARNING' CONCEPT, AS OPPOSED TO 'FIXING' AN ENVIRONMENTAL PROBLEM VIA A WELL-ESTABLISHED METHOD. TO THE EXTENT PRACTICABLE, RECIPIENT'S WORK MUST EMBODY INNOVATION. INNOVATION FOR THE PURPOSES OF THIS RFA IS DEFINED AS THE PROCESS OF MAKING CHANGES; A NEW METHOD, CUSTOM OR DEVICE. INNOVATION CAN TAKE THE FORM OF WHOLLY NEW APPLI

SINGLE CELL RESOLUTION OMICS ANALYSIS OF T1D ISLETS

NEXT-GENERATION ULTRA-HIGH RESOLUTION ION MOBILITY SPECTROMETER FOR METABOLOMICS - METABOLISM IS ESSENTIAL TO HUMAN HEALTH AND ITS STUDY VIA METABOLOMICS IS CRUCIAL TO BIOMEDICAL RESEARCH. HOWEVER, CURRENT PLATFORMS FOR MEASURING METABOLITES THAT COMBINE CHROMATOGRAPHY SEPARATIONS WITH MASS SPECTROMETRY HAVE LIMITATIONS. THIS PROJECT AIMS TO DEVELOP A NEW PLATFORM THAT PROVIDES ULTRA-HIGH ION MOBILITY RESOLUTION AND SENSITIVITY TO SMALL CHANGES IN THE METABOLITE STRUCTURE. THE PROJECT WILL ALSO DEVELOP A HIGHLY PRECISE COLLISION CROSS-SECTION CALCULATOR THAT UTILIZES THE NEW PLATFORM'S ULTRA-HIGH-RESOLUTION DATA. THESE DEVELOPMENTS WILL ENABLE HIGHER QUALITY AND MORE COMPREHENSIVE METABOLOMICS MEASUREMENTS BY DISTINGUISHING BETWEEN CHALLENGING ISOMERS SUCH AS ISOTOPOMERS. THE KEY DEVELOPMENTS WILL BE THE IMPLEMENTATION OF GREATLY IMPROVED ION MOBILITY SEPARATIONS AND HIGHLY PRECISE PROPERTY PREDICTIONS. THESE DEVELOPMENTS WILL PROVIDE MUCH GREATER RESOLUTION, HIGHER SPEED, BROADER APPLICABILITY TO METABOLITE CHEMICAL CLASSES, AND IMPROVED SENSITIVITY AND MEASUREMENT DYNAMIC RANGE IN CONJUNCTION WITH MASS SPECTROMETRY. THE NEW PLATFORM DEVELOPMENT EFFORTS WILL INCLUDE THE ESSENTIAL PLATFORM CONTROL AND DATA ACQUISITION CAPABILITIES, RESULTING IN A PLATFORM READY FOR INITIAL METABOLOMICS APPLICATIONS AND DISSEMINATION.

CV INFRASTRUCTURE - URBAN BUS OPS SAFETY

REGULATORY NETWORKS AND BIOMARKERS OF BETA-CELL DYSFUNCTION AND APOPTOSIS

REAL-TIME MEASUREMENT AND UPTAKE OF CARCINOGENS BY MENTHOL CIGARETTE SMOKERS

DETECTION OF TOXINS: A COMBINED ELISA MICROARRAY AND ACTIVITY ASSAY PLATFORM

DE-FE0031782 BATTELLE MEMORIAL INSTITUTE USING NATURAL GAS LIQUIDS TO RECOVER UNCONVENTIONAL OIL AND GAS RESOURCES

ULTRA-HIGH RESOLUTION GAS PHASE SEPARATION AND ANALYSIS PLATFORM FOR METABOLOMICS

ENVIRONMENTAL/BEHAVIORAL FACTORS SHAPING CIRCUMCISION DECISIONS IN ZIMBABWE

THE PURPOSE OF THIS PROJECT IS TO ESTABLISH A FOUNDATION FOR A CARBON CAPTURE AND STORAGE (CCS) HUB IN SELECTED PARTS OF THE MID-ATLANTIC OUTER CONTINENTAL SHELF (OCS) FROM VIRGINIA TO MASSACHUSETTS. THE PROJECT WILL ASSIST INDUSTRY AND COMMUNITIES IN EVALUATING VIABILITY OF MULTIPLE DESIGN SCENARIOS.

DE-FE0032160 BATTELLE MEMORIAL INSTITUTE PROJECT TITLED NUCLEAR DIRECT AIR CAPTURE WITH CARBON STORAGE (NUDACCS) NEW AWARD

'AEROSPACE MEDICINE, CLINICAL RESEARCH, HUMAN SYSTEMS INTEGRATION RESEARCH, AND EXPEDITIONARY MEDICINE'

INTEGRATED RISK ASSESSMENT AND MOLECULAR CHARACTERIZATION OF PULMONARY RESPONSE TO E-CIGARETTE EXPOSURE

DE-FE0031850, BATTELLE MEMORIAL INSTITUTE, TITLED ''WIRELESS MICROSENSORS SYSTEM FOR MONITORING DEEP SUBSURFACE OPERATIONS.''

A PROTEOMICS PLATFORM FOR QUANTITATIVE, ULTRA-HIGH THROUGHPUT, AND ULTRA-SENSITIV

UNDIAGNOSED DISEASES NETWORK METABOLOMICS CORE SUPPLEMENT

MULTIPLEX SENSOR PLATFORM FOR BIOLOGICAL MONITORING

THE IMPACT OF BRAIN LIPOPROTEIN STRUCTURE AND COMPOSITION ON AMYLOID BETA METABOLISM AND ALZHEIMER'S DISEASE - PROJECT SUMMARY/ABSTRACT ALZHEIMER'S DISEASE (AD) IS A DEBILITATING BRAIN DISORDER CHARACTERIZED BY MEMORY LOSS AND COGNITIVE DECLINE, AFFECTING MILLIONS WORLDWIDE. THE INTRICATE INTERPLAY BETWEEN LIPID METABOLISM AND AD PATHOLOGY IS INCREASINGLY RECOGNIZED, AND BRAIN LIPOPROTEINS (BLPS) ARE THOUGHT TO BE KEY PLAYERS GIVEN THEY SERVE AS THE PRIMARY LIPID TRANSPORT VEHICLES IN THE CENTRAL NERVOUS SYSTEM (CNS). BLPS RESIDE IN THE CEREBROSPINAL FLUID (CSF) THAT BATHES THE BRAIN BUT UNFORTUNATELY, DUE TO THEIR LOW ABUNDANCE AND LIMITED ACCESSIBILITY, A COMPREHENSIVE UNDERSTANDING OF BLPS HAS REMAINED ELUSIVE. WE DEVELOPED A FLUORESCENT LIPOPROTEIN PROFILING (FLP) TECHNOLOGY THAT HURDLES THIS ABUNDANCE PROBLEM TO DEEPLY CHARACTERIZE BLPS IN SMALL VOLUMES OF CSF. USING OUR FLP AND MASS SPECTROMETRY (LC-MS/MS), WE REVEALED THAT BLPS CONSIST OF A SPECTRUM OF DISCRETELY SIZED SUBPOPULATIONS THAT EXHIBIT REMARKABLE PROTEOMIC DIVERSITY. WE POSIT THAT THE DOMINANT ORGANIZING SCAFFOLD ON BLPS, APOLIPOPROTEIN (APO)E, ACTS AS A MASTER REGULATOR OF BLP COMPOSITION BY ADOPTING DISTINCT STRUCTURAL CONFORMATIONS TO FACILITATE DOCKING WITH COMPLEMENTARY PARTNERS THAT IMPART UNIQUE FUNCTIONS. APOE HAS THREE ISOFORMS—E2, E3, AND E4 DIFFERENTIATED BY CYSTEINE-ARGININE MUTATIONS AT RESIDUES 112 AND 158 AND CARRIERS OF APOE4 HAVE INCREASED AMYLOID PLAQUE BURDEN, AND SUBSTANTIALLY INCREASED LIFETIME RISK FOR DEVELOPING AD. WE HYPOTHESIZE THAT CONFORMATIONAL DIFFERENCES BETWEEN APOE ISOFORMS ALTER BLP COMPOSITIONAL SIGNATURES AND THEIR ABILITY TO BIND AND TRAFFIC AMYLOID BETA (AΒ), THE BUILDING BLOCK OF AMYLOID PLAQUES. OUR OBJECTIVES ARE TWO-FOLD: FIRST, TO ASSESS THE IMPACT OF APOE ISOFORMS ON BLP DISTRIBUTION, COMPOSITION, AND ABILITY TO BIND AΒ. TO DO SO, WE WILL PERFORM A COMPARATIVE ANALYSIS OF BLP PATTERNS IN INDIVIDUALS WITH DIFFERENT APOE GENOTYPES AND LEVELS OF COGNITIVE HEALTH USING OUR FLP AND LC-MS/MS, SHEDDING LIGHT ON THE AD-RELEVANT BLP SUBSPECIES. SECOND, WE AIM TO UNRAVEL THE STRUCTURAL DETAILS OF LIPID-BOUND APOE ISOFORMS THAT GOVERN THEIR INTERACTIONS WITH AΒ. USING CRYO-EM AND NOVEL STRUCTURAL PROTEOMICS APPROACHES, WE WILL DERIVE HIGH-RESOLUTION STRUCTURAL MAPS OF AΒ COMPLEXED WITH DIFFERENT APOE ISOFORMS ON RECONSTITUTED HDL AND DETERMINE HOW “ACCESSORY” PROTEINS FOUND ON BLPS MODULATE THEIR INTERACTION WITH AΒ. THESE STUDIES WILL PROVIDE A DETAILED MOLECULAR MAP OF BLP METABOLISM IN THE CNS WHICH CAN BE LEVERAGED FOR THE DEVELOPMENT OF TARGETED THERAPEUTIC APPROACHES TO TREAT AND PREVENT AD.

MULTISCALE MODELING OF CIRCADIAN RHYTHMS

PLATFORM PROVIDING INCREASED THROUGHPUT, SENSITIVITY AND SPECIFICITY FOR METABOLO

A UNIVERSAL MULTIPLEX ASSAY SYSTEM FOR HIGH-THROUGHPUT CLINICAL APPLICATIONS

STATIONARY FUEL CELL SYSTEM COST ANALYSIS

MAINSTREAM SMOKE COMPOSITION AND TOXIN EXPOSURE FROM PROTOTYPICAL CIGAR PRODUCTS

RAPID ASSAY FOR INTERNALIZED RADIONUCLIDES WITH ADVANCED MATERIALS AND METHODS

PROTEOMICS STUDIES OF TYPE 2 DIABETES USING KNOCKOUT MOUSE MODELS

INNOVATIVE BIOMONITORING DEVICE FOR RAPID DIAGNOSIS OF EXPOSURE TO NERVE AGENTS

PROJECTIONS PF LAND USE CHANGE&THE CARBON CYCLE

DE-FE0031686 ''A NON INVASIVE APPROACH FOR ELUCIDATING THE SPATIAL DISTRIBUTION OF IN-SITU STRESS IN DEEP SUBSURFACE GEOLOGIC FORMATIONS CONSIDERED FOR CO2 STORAGE''

KEY EVENTS IN MODULATION OF LUNG INFECTION SUSCEPTIBILITY BY NANOMATERIALS

MASSIVE SINGLE CELL PROTEOMICS FOR CANCER BIOLOGY - PROJECT SUMMARY/ABSTRACT SINGLE-CELL TECHNOLOGIES HAVE BECOME THE CORNERSTONE OF BIOMEDICAL AND CELL BIOLOGY RESEARCH. NEXT- GENERATION SEQUENCING-BASED TECHNOLOGIES HAVE ENABLED LARGE-SCALE CHARACTERIZATION OF TRANSCRIPT EXPRESSIONS IN SINGLE CELLS FROM CLINICAL SPECIMENS AND REVEAL UNEXPECTED CELLULAR HETEROGENEITY RELATED TO PATHOGENESIS. HOWEVER, MANY INTEGRATIVE STUDIES HAVE SHOWN ONLY LOW TO MODERATE CORRELATIONS BETWEEN THE ABUNDANCE OF RNA TRANSCRIPTS AND THEIR CORRESPONDING PROTEINS, THE MAIN DETERMINANTS OF CELL PHENOTYPE. WE HYPOTHESIZE MASS SPECTROMETRY-BASED SINGLE-CELL PROTEOMICS COULD PROVIDE DIRECT INSIGHT ON THE CELLULAR HETEROGENEITY AND INFORM PROTEIN MARKERS RELATED TO DISEASE PROGRESSION AND RESISTANCE TO THERAPY. THE OVERALL OBJECTIVE OF THIS PROJECT IS TO DEVELOP A HIGH THROUGHPUT SINGLE-CELL PROTEOMICS (SCPROTEOMICS) PLATFORM TO ENABLE THE ROUTINE ANALYSIS OF >10,000 SINGLE CELLS AT A DEPTH OF 2000 PROTEINS IN A COST-EFFICIENT WAY. THE DEVELOPED TECHNOLOGY WILL BE DISSEMINATED TO THE RESEARCH COMMUNITY THROUGH CLOSE COLLABORATION WITH A COMMERCIAL PARTNER. WE WILL ALSO APPLY SCPROTEOMICS TO INTERROGATE THE HETEROGENEITY OF BOTH MALIGNANT PLASMA CELL AND IMMUNE CELL POPULATIONS FROM MULTIPLE MYELOMA PATIENTS. WE WILL PURSUE THESE GOALS THROUGH THREE SPECIFIC AIMS: 1) TO ESTABLISH AN ULTRA-HIGH THROUGHPUT SINGLE-CELL PREPARATION METHOD BY COUPLING AN ENHANCED MULTIPLEXING METHOD WITH HIGH-DENSITY NESTED NANOPOTS CHIPS AND MULTI-CHANNEL DROPLET DISPENSING SYSTEM; WE AIM TO PROCESS >2000 CELLS IN A SINGLE MICROCHIP, AND MULTIPLEX-LABEL 36 SINGLE CELLS FOR A SINGLE LC-MS ANALYSIS; 2) TO ADVANCE THE THROUGHPUT, SENSITIVITY, AND QUANTITATION ACCURACY OF LC-MS SYSTEM. A DUAL-COLUMN NANOLC SYSTEM AND A FAIMS-BASED MS ACQUISITION METHOD WILL BE DEVELOPED TO ENABLE THE ANALYSIS OF >860 CELLS PER DAY WITH HIGH QUANTITATION PRECISION; 3) TO APPLY SCPROTEOMICS TO PROFILE ~10,000 PLASMA AND IMMUNE CELLS FROM MM PATIENTS. WE WILL INTEGRATE SCPROTEOMICS WITH EXISTING SCRNA-SEQ DATA TO EXPLORE TUMOR HETEROGENEITY, CHIMERIC ANTIGEN RECEPTOR T-CELLS (CAR-T) MARKERS, AND THE IMMUNE MICROENVIRONMENT IN MULTIPLE MYELOMA. THIS RESEARCH IS HIGHLY INNOVATIVE BECAUSE THE PROPOSED SINGLE-CELL PROTEOMICS PLATFORM WILL BE THE FIRST OF ITS KIND TO ROUTINELY AND RELIABLY CHARACTERIZE > 10,000 SINGLE CELLS AT A THROUGHPUT COMPARABLE TO SINGLE-CELL TRANSCRIPTOMICS. IT IS ALSO THE FIRST SCPROTEOMICS STUDY OF PRIMARY LIQUID TUMOR CELLS ISOLATED FROM THE PATHOLOGICAL ENVIRONMENT, E.G. BONE MARROW OF MM PATIENTS. STATEMENT OF IMPACT: TUMOR HETEROGENEITY HAS INDISPENSABLE IMPLICATIONS IN CANCER EVOLUTION, TUMORAL SPATIAL ORGANIZATION, AND CLINICAL TREATMENT. SINGLE-CELL PROTEOMICS COULD PROVIDE A BASIS TO UNRAVEL THESE COMPLICATED RELATIONSHIPS AND TO CLARIFY THE MECHANISMS OF CANCER PROGRESSION AND SUBCLONE RESISTANCE TO THERAPEUTIC TREATMENTS.

DESCRIPTION:THE PURPOSE OF THIS COOPERATIVE AGREEMENT IS TO IMPROVE ENVIRONMENTAL GOVERNANCE IN REGIONS/COUNTRIES - THAT ARE ENGAGED IN AN FREE TRADE AGREEMENTS WITH THE U.S. OR COOPERATE WITH THE U.S. THROUGH OTHER BILATERAL ENVIRONMENTAL INITIATIVE(S). IMPROVING ENVIRONMENTAL GOVERNANCE MAY BE ACCOMPLISHED THROUGH THE EXCHANGE OF EXPERT KNOWLEDGE OF ENVIRONMENTAL QUALITY MANAGEMENT STRATEGIES, TOOLS, INFORMATION, AND PROGRAMS. THE OVERARCHING COMPONENT UNDER THIS COOPERATIVE AGREEMENT IS GOOD ENVIRONMENTAL GOVERNANCE. THE SPECTRUM OF THE CAPACITY BUILDING ACTIVITIES EXPECTED TO BE PERFORMED SUPPORTS THE FOLLOWING ENVIRONMENTAL AREAS, INCLUDING BUT NOT LIMITED TO: (1) WATER RESOURCES MANAGEMENT MDASH;; (2) SOLID WASTE MANAGEMENT; (3) AIR QUALITY MANAGEMENT; (4) EMERGENCY RESPONSE CAPACITY;(5) ENVIRONMENTAL IMPACT ASSESSMENTS (EIA); (6) PUBLIC PARTICIPATION/SOCIAL INCLUSION; ENVIRONMENTAL JUSTICE AND EQUITY; AND (7) ENVIRONMENTAL ENFORCEMENT AND COMPLIANCE.ACTIVITIES:THE EXCHANGE OF INFORMATION, AND ENVIRONMENTAL TECHNICAL EXPERTISE TO BE PERFORMED MAY INCLUDE SEMINARS, TRAINING, WORKSHOPS (VIRTUAL AND/OR IN-PERSON) STUDY TOURS AMONG OTHERS. THE AREAS OF TECHNICAL CAPACITY BUILDING WILL BE FOCUSED ON WATER QUALITY, AIR QUALITY, SOLID WASTE MANAGEMENT, CLIMATE CHANGE, ENVIRONMENTAL JUSTICE, PUBLIC PARTICIPATION, EMERGENCY RESPONSE, ENVIRONMENTAL IMPACT ASSESSMENT, AND ENVIRONMENTAL ENFORCEMENT AND COMPLIANCE. SUBRECIPIENT:SUBAWARDS ACTIVITIES MAY INCLUDE ON-THE-GROUND FEASIBILITY STUDIES, DEVELOPMENT OF CASE STUDIES, IMPLEMENTATION OF THE TRASH FREE WATERS APPROACH THAT WOULD LEAD TO THE DEVELOPMENT OF A NATIONAL MARINE LITTER ACTION PLAN. OUTCOMES:EXPECTED OUTCOMES WOULD INCLUDE: 1) INCREASED TECHNICAL CAPACITY IN VARIOUS ENVIRONMENTAL AREAS (I.E., WATER, SOLID WASTE, AIR QUALITY) IN U.S. TRADING PARTNER COUNTRIES AND KEY BILATERAL COUNTERPARTS ABROAD. 2) ENHANCED ENVIRONMENTAL GOVERNANCE IN U.S. TRADING PARTNER COUNTRIES AND KEY BILATERAL COUNTERPARTS ABROAD. INTENDED BENEFICIARIES WOULD BE THE U.S. ENVIRONMENTAL AUTHORITIES COUNTERPARTS: MINISTRIES OF ENVIRONMENT AND LOCAL MUNICIPALITIES AND COMMUNITIES AS WELL AS OTHER RELEVANT ORGANIZATIONS AND THEIR CONSTITUENCIES.

MIDWEST REGIONAL CARBON SEQUESTRATION PARTNERSHIP

SYSTEMATIC VALIDATION OF BIOMARKERS PREDICTIVE OF IA AND T1D AND THEIR RELATIONSHIP WITH DISEASE DEVELOPMENT - SUMMARY: TYPE 1 DIABETES (T1D) IS A METABOLIC DISEASE CURRENTLY WITHOUT A CURE THAT RESULTS IN DESTRUCTION OF INSULIN- PRODUCING Β CELLS OF THE PANCREAS VIA AN AUTOIMMUNE RESPONSE. T1D TREATMENT REQUIRES INSULIN ADMINISTRATION AND GREATLY REDUCES LIFE QUALITY AND EXPECTANCY. DEVELOPMENT AND PERSISTENCE OF ISLET AUTOIMMUNITY (IA) CAN BE DETERMINED BY CIRCULATING AUTOANTIBODIES AGAINST ISLET PROTEINS. HOWEVER, NOVEL BIOMARKERS ARE NEEDED TO: 1) BETTER UNDERSTAND THE MECHANISMS THAT TRIGGER AND DRIVE IA; AND 2) PREDICT INDIVIDUAL PROGRESSION THROUGH THE STAGES OF THE DISEASE. TO IDENTIFY NEW BIOMARKERS, WE HAVE RECENTLY COMPLETED A PLASMA PROTEOMICS ANALYSIS FOR THE ENVIRONMENTAL DETERMINANTS OF DIABETES IN THE YOUNG (TEDDY). THIS NESTED CASE-CONTROL STUDY 1 (NCC1) INCLUDED 401 CHILDREN WHO DEVELOPED IA (AT MEDIAN AGE OF 21 MONTHS) AND 94 CHILDREN WHO PROGRESSED TO CLINICAL T1D (AT MEDIAN AGE OF 29 MONTHS), MATCHED AGAINST CONTROLS. WE IDENTIFIED 376 PROTEINS AS CANDIDATE BIOMARKERS; 83 OF THESE PROTEINS WERE VALIDATED AS SIGNIFICANT PREDICTORS OF EITHER IA OR PROGRESSION TO T1D IN LONGITUDINAL ANALYSES OF 6,426 SAMPLES. WE ALSO IDENTIFIED PANELS OF PROTEINS THAT CAN PREDICT, WITH HIGH ACCURACY, DEVELOPMENT OF ISLET AUTOIMMUNITY (AUC=0.918) AND PROGRESSION TO T1D (AUC=0.871) 6 MONTHS PRIOR TO SEROCONVERSION BY MACHINE LEARNING ANALYSIS. LIMITATIONS OF THE TEDDY NCC1 INCLUDED LIMITED FOLLOW-UP AND VERY YOUNG AGE (≤6 YEARS) OF THE PARTICIPANTS. IA AND PROGRESSION TO T1D CAN OCCUR OVER A MUCH BROADER AGE RANGE, AND THE CELLULAR AND SYSTEMIC PROCESSES INVOLVED MAY DIFFER IN YOUNGER VS OLDER CHILDREN. IN THE NEXT CASE CONTROL STUDY 2 (NCC2), TEDDY MONITORED INDIVIDUALS UNTIL 15 YEARS OF AGE, AN ADDITIONAL 501 PARTICIPANTS DEVELOPED IA (AT MEDIAN AGE OF 89 MONTHS) AND AN ADDITIONAL 345 PROGRESSED TO T1D (AT MEDIAN AGE OF 108 MONTHS). HERE WE PROPOSE TO PERFORM A LONGITUDINAL ANALYSIS OF THE NCC2 SAMPLES WITH A HIGHLY MULTIPLEXED, SENSITIVE, AND ROBUST TARGETED PROTEOMICS ANALYSIS TO SIMULTANEOUSLY VALIDATE BIOMARKERS IDENTIFIED IN THE NCC1 AND TO PROVIDE INFORMATION ABOUT THE BIOLOGICAL PROCESSES REGULATED DURING DISEASE DEVELOPMENT. MORE SPECIFICALLY, WE PROPOSE THE FOLLOWING SPECIFIC AIMS: (I) VALIDATE PREDICTIVE BIOMARKERS OF ISLET AUTOIMMUNITY; (II) VALIDATE PREDICTIVE BIOMARKERS OF PROGRESSION TO T1D; AND (III) DETERMINE MECHANISMS UNDERLYING DEVELOPMENT OF IA AND PROGRESSION TO T1D. TO FULFILL THESE AIMS WE WILL PERFORM A LARGE-SCALE TARGETED PROTEOMICS ANALYSIS OF 8 TIME POINTS FROM 48 MONTHS PRE-SEROCONVERSION TO 12 MONTHS POST-SEROCONVERSION OF INDIVIDUALS THAT ONLY DEVELOPED ISLET AUTOIMMUNITY AND INDIVIDUALS THAT DEVELOPED CLINICAL DIABETES, PAIRED WITH CONTROLS, TOTALING 6,400 SAMPLES. THE RESULTS OF THIS PROJECT SHOULD BRING THE FIELD ONE STEP CLOSER TO DEVELOPING CLINICAL BIOMARKERS AND ASSOCIATED ASSAYS THAT CAN PREDICT ALL PHASES OF T1D DEVELOPMENT IN ADDITION TO IDENTIFYING POSSIBLE CAUSES. THIS KNOWLEDGE GAINED WILL LIKELY OPEN OPPORTUNITIES TO DEVELOP PREVENTIVE INTERVENTIONS AGAINST T1D.

LEVERAGING REGIONAL EXPLORATION TO DEVELOP GEOLOGIC FRAMEWORK FOR CO2 STORAGE IN DEEP FORMATIONS

SERUM PROTEIN BIOMARKERS FOR PREDICTING TYPE 1 DIABETES

SLOW-MAS NMR METABOLOMICS

A NOVEL HIGH RESOLUTION MS PLATFORM FOR HIGH-THROUGHPUT SCREENING OF G PROTEIN-COUPLED RECEPTORS - SUMMARY: MASS SPECTROMETRY (MS) HAS PROVEN INVALUABLE IN STUDYING THE MECHANISMS OF CELLULAR SIGNALING AS MS PLATFORMS CAN DIRECTLY PROVIDE AMINO ACID RESIDUE SITE-SPECIFIC PHOSPHORYLATION DATA COMPARED TO TRADITIONAL ANTIBODY-BASED APPROACHES. HOWEVER, LIMITATIONS EXIST IN CURRENT MS APPROACHES IN GENERATING CONFIDENT SITE-SPECIFIC PHOSPHORYLATION QUANTIFICATION. THIS IS PARTICULARLY EVIDENT IN COMPLEX MULTI-PHOSPHORYLATED PROTEIN MOTIFS, WHERE THE DETECTION OF ISOMERIC MULTI-PHOSPHORYLATED PEPTIDES EASILY OVERWHELMS ANY PREDICTION SCORING APPROACH THAT IS SIMPLY BASED UPON THE FRAGMENTATION SPECTRA. THERE ARE MANY BIOLOGICAL EXAMPLES OF HYPERPHOSPHORYLATED REGIONS, WHERE THEY ARE ASSOCIATED WITH RECEPTOR/LIGAND INTERACTIONS, INCLUDING G-PROTEIN COUPLED RECEPTORS (GPCRS), MEMBRANE RECEPTORS THAT ARE THE MOST COMMON TARGETS FOR FDA-APPROVED DRUGS. FOR ACCURATE SITE-SPECIFIC QUANTIFICATION OF PROTEIN HYPERPHOSPHORYLATION WE PROPOSE A TRANSDISCIPLINARY APPROACH USING ULTRAHIGH RESOLUTION ION MOBILITY SEPARATION (IMS) INTEGRATED WITH HIGHLY ACCURATE AND SENSITIVE MS AND MS/MS SPECTRA TO ENABLE THE CONFIDENT CHARACTERIZATION OF HYPERPHOSPHORYLATED GPCR ENSEMBLES WITH GREATLY IMPROVED SENSITIVITY, AND SPEED. WE WILL USE MULTI-LEVEL STRUCTURES FOR LOSSLESS ION MANIPULATIONS (SLIM) TECHNOLOGY (SLIM-ORBITRAP PLATFORM) TO FULLY CHARACTERIZE PHOSPHORYLATION OF GPCR/ANTAGONIST INTERACTIONS UTILIZING CXCR3, WHICH PLAYS A CENTRAL ROLE IN INFLAMMATORY DISEASES THROUGH ITS REGULATION OF T CELL FUNCTION AS AN INITIAL TEST CASE. WE PLAN TO FIRST INTEGRATE ULTRAHIGH RESOLUTION IMS WITH AN ADVANCED ORBITRAP MS PLATFORM FOR UNAMBIGUOUS DECODING OF HYPERPHOSPHORYLATED SITES, EVALUATE THE SLIM-ORBITRAP MS PLATFORM FOR RESOLVING HYPERPHOSPHORYLATED PROTEIN REGIONS, AND FINALLY, PERFORM COMPREHENSIVE SITE-SPECIFIC PHOSPHOPROTEOMICS FOR GPCRS THROUGH SCREENING OF ACTIVATED T CELLS WITH DOSE-RESPONSES OF CHEMOKINE AND SMALL-MOLECULE CXCR3 BIASED AGONISTS.

ENZYME ACTIVITY ENHANCEMENT IN FUNCTIONALIZED NANOPOROUS SUPPORT

ACCELNET-IMPLEMENTATION: GLOBAL ECOSYSTEM RESEARCH INFRASTRUCTURE (GERI): HARMONIZING DATA TO ADDRESS ECOLOGICAL DROUGHT -DROUGHT IS INCREASINGLY BECOMING MORE COMMON DUE TO CLIMATE CHANGE, HUMAN WATER USAGE, AND CHANGES IN LAND USE. IT HAS SIGNIFICANT IMPACTS ON ECOSYSTEMS AND PEOPLE'S WELL-BEING, BUT THERE IS STILL MUCH WE DON'T KNOW ABOUT ITS EFFECTS ON ECOSYSTEMS AND SOCIETY. TO DEEPEN OUR UNDERSTANDING, ENVIRONMENTAL RESEARCH INFRASTRUCTURES (ERIS) HAVE BEEN ESTABLISHED WORLDWIDE TO COLLECT CRITICAL DATA. THESE ERIS PROVIDE A UNIQUE OPPORTUNITY TO STUDY HOW DROUGHT AND OTHER ENVIRONMENTAL CHANGES IMPACT NATURE ACROSS DIFFERENT REGIONS AND OVER EXTENDED PERIODS OF TIME. SIX OF THESE ERIS FROM DIFFERENT PARTS OF THE WORLD HAVE COME TOGETHER TO FORM THE GLOBAL ECOSYSTEM RESEARCH INFRASTRUCTURE (GERI). GERI'S OBJECTIVE IS TO FOSTER COLLABORATION AND INFORMATION SHARING AMONG THESE NETWORKS. THE AIM IS TO ESTABLISH EFFECTIVE COMMUNICATION PATHWAYS BETWEEN DIFFERENT COUNTRIES AND CULTURES. THIS PROPOSAL BUILDS UPON THEIR PREVIOUS WORK AND SEEKS TO CAPITALIZE ON THIS GLOBAL COLLABORATION IN SEVERAL WAYS: FIRSTLY, THIS WORK AIMS TO STRENGTHEN AND EXPAND INTERNATIONAL COLLABORATIONS BY WORKING CLOSELY WITH OTHER RESEARCH NETWORKS. THE SECOND FOCUS WILL BE ON STUDYING DROUGHT ON A GLOBAL SCALE USING THE DATA SHARED ACROSS THE PARTNER ERIS. THIS APPROACH WILL ENABLE THEM TO GAIN INSIGHTS INTO HOW DROUGHT IMPACTS ECOSYSTEMS WORLDWIDE. THIRDLY, THIS PROJECT SEEKS TO ACCELERATE SCIENTIFIC DISCOVERIES BY BRINGING SCIENTISTS AND STAKEHOLDERS FROM DIFFERENT COUNTRIES TOGETHER. FINALLY, WE WILL TRAIN AND SUPPORT THE NEXT GENERATION OF RESEARCHERS BY ORGANIZING WORKSHOPS AND CREATING MORE OPPORTUNITIES FOR COLLABORATION. OVERALL, THIS COLLABORATION BETWEEN RESEARCH NETWORKS WILL CONTRIBUTE TO A BETTER UNDERSTANDING OF THE EFFECTS OF DROUGHT ON ECOSYSTEMS AND HUMAN LIFE BY FACILITATING THE EXCHANGE OF KNOWLEDGE AND DATA ON A GLOBAL SCALE. INCREASINGLY INFLUENCED BY ANTHROPOGENIC CLIMATE CHANGE, HUMAN WATER USE, AND EXPANDING LAND-USE CHANGE, DROUGHT IS ENTERING UNFAMILIAR TERRITORY. DESPITE THE INFLUENCE OF DROUGHT ON ECOSYSTEM FUNCTION, AND HUMAN WELL-BEING, THERE ARE SIGNIFICANT UNCERTAINTIES IN OUR UNDERSTANDING OF THE IMPACTS OF DROUGHT FOR ECOSYSTEMS AND HUMANITY. OVER THE PAST DECADE, LARGE ENVIRONMENTAL RESEARCH INFRASTRUCTURES (ERIS) HAVE BEEN IMPLEMENTED AROUND THE WORLD TO DRIVE UNDERSTANDING OF THE RESPONSES OF THE BIOSPHERE TO ENVIRONMENTAL CHANGE. THESE EMERGENT ERIS NOW PROVIDE A UNIQUE OPPORTUNITY TO ADVANCE OUR UNDERSTANDING OF ECOLOGICAL PROCESSES, SUCH AS DROUGHT, ACROSS CONTINENTS, DECADES, AND DISCIPLINARY BOUNDARIES. AGAINST THIS BACKDROP, SIX ERIS FROM AROUND THE WORLD HAVE COME TOGETHER TO ESTABLISH AN INTERNATIONAL NETWORK-TO-NETWORK COLLABORATION ? THE GLOBAL ECOSYSTEM RESEARCH INFRASTRUCTURE (GERI). GERI ACTIVITIES HAVE FOCUSED ON GARNERING SUPPORT AND ESTABLISHING BASELINE PATHWAYS FOR COMMUNICATIONS ACROSS CONTINENTS AND CULTURES. THIS PROPOSAL EXPANDS UPON PREVIOUS ACTIVITIES TO REALIZE THE POWER OF GLOBAL NETWORK TO NETWORK COLLABORATIONS BY: (I) FURTHER DEVELOPING AND LEVERAGING STRATEGIC INTERNATIONAL NETWORK-TO-NETWORK COLLABORATIONS VIA ENGAGING NEW PARTNERS IN CENTRAL AMERICA AND CONTINUING EXISTING PARTNERSHIPS, (II) DEMONSTRATING THE UTILITY OF HARMONIZED GERI DATA VIA A STRATEGIC INITIAL FOCUS ON ECOLOGICAL DROUGHT AT A GLOBAL SCALE, (III) ACCELERATING SCIENTIFIC DISCOVERY BY BRINGING TOGETHER INTERNATIONAL STAKEHOLDERS AND RESEARCHERS TO GUIDE THE HARMONIZATION OF THESE DATA AND USE THEM TO ADVANCE KNOWLEDGE, AND (IV) PREPARING THE NEXT GENERATION OF RESEARCHERS IN THIS NETWORK-OF-NETWORK APPROACH VIA WORKSHOPS, TRAINING, AND ENHANCED OPPORTUNITIES FOR COLLABORATION. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.

TARGETED PROTEOMICS TECHNOLOGY FOR ACCURATE QUANTITATIVE SINGLE-CELL PROTEOMICS - ABSTRACT MULTI-OMICS CHARACTERIZATION OF A BROAD SPECTRUM OF SMALL SUBPOPULATIONS OF CELLS BETWEEN TUMORS AND WITHIN INDIVIDUAL TUMORS AT THE SINGLE-CELL RESOLUTION IS CRUCIAL TO ACHIEVE UNDERSTANDING OF A COMPLETE DISEASE BIOLOGY. FURTHERMORE, BIOLOGICALLY IMPORTANT CLINICAL SPECIMENS ARE AVAILABLE IN LOW QUANTITY (E.G., <10 TUMOR CELLS), REQUIRING ADVANCED SINGLE-CELL TECHNOLOGIES FOR EFFECTIVE ANALYSIS. HOWEVER, SINGLE-CELL PROTEOMICS TECHNOLOGIES ARE LAGGING FAR BEHIND OTHER OMICS TECHNOLOGIES. ANTIBODY-BASED IMMUNOASSAYS ARE USED PRIMARILY FOR TARGETED SINGLE-CELL PROTEOMICS, BUT THEY HAVE INHERENT LIMITATIONS (E.G., LOW MULTIPLEX), AND GENERALLY LACK QUANTITATION ACCURACY. MASS SPECTROMETRY (MS)-BASED TARGETED PROTEOMICS HAS EMERGED AS AN ALTERNATIVE FOR BROAD ACCURATE QUANTIFICATION. HOWEVER, CURRENT SINGLE-CELL MS CAN ONLY ALLOW FOR RELATIVE QUANTIFICATION OF ~870 PROTEINS FROM SINGLE MAMMALIAN CELLS. THERE ARE THREE MAJOR CHALLENGES IN SINGLE-CELL MS FOR ACCURATE QUANTITATIVE SINGLE-CELL PROTEOMICS: 1) INEFFECTIVE PROCESSING OF SINGLE CELLS, 2) INSUFFICIENT MS SENSITIVITY AND LOW SAMPLE THROUGHPUT, AND 3) LACKING WELL-CHARACTERIZED UNIVERSAL INTERNAL STANDARD (UIS). TO ADDRESS THESE CHALLENGES, WE PROPOSE TO DEVELOP A SINGLE-CELL MS SYSTEM FOR RAPID ACCURATE ANALYSIS OF SINGLE-CELL PROTEOME. THE FEASIBILITY IS STRONGLY SUPPORTED BY OUR RECENT PROGRESS IN MANY ASPECTS OF TECHNOLOGY DEVELOPMENT (E.G., INTRODUCING THE `CARRIER' CONCEPT FOR EFFECTIVE PROCESSING OF SMALL NUMBERS OF CELLS INCLUDING SINGLE CELLS, AND DEVELOPING DISRUPTIVE MS TECHNOLOGIES TO IMPROVE MS DETECTION SENSITIVITY AND SPECIFICITY) AS WELL AS OUR EXTENSIVE EXPERIENCES IN HIGH- RESOLUTION LIQUID CHROMATOGRAPHY (LC) SEPARATION FOR SENSITIVE DETECTION AND TARGETED PROTEOMICS ANALYSIS FOR ABSOLUTE QUANTIFICATION OF SIGNALING PATHWAY PROTEINS. THE SINGLE-CELL MS SYSTEM WILL BE DEVELOPED THROUGH 1) ESTABLISHING SUPER-SILAC (STABLE ISOTOPE LABELING WITH AMINO ACIDS IN CELL CULTURE) AS BOTH PROTEOME CARRIER AND UIS, 2) INCORPORATION OF PROTEOME CARRIER SUPER-SILAC (CSILAC) INTO THE SAMPLE PREPARATION WORKFLOW FOR ROBUST PROCESSING OF SINGLE CELLS, AND 3) LEVERAGING CUTTING-EDGING LC AND MS TECHNOLOGIES DEVELOPED AT PNNL WITH INTEGRATION OF ULTRALOW-FLOW LC SEPARATION, HIGH-EFFICIENCY ION SOURCE (THE COMBINATION OF AN EMITTER ARRAY TECHNOLOGY AND SUB-AMBIENT PRESSURE IONIZATION WITH NANOELECTROSPRAY), AND ULTRAFAST HIGH-RESOLUTION ION MOBILITY SEPARATION FOR SIGNIFICANTLY IMPROVING BOTH MS SENSITIVITY AND SAMPLE THROUGHPUT. SUPER-SILAC WILL BE CHARACTERIZED AS UIS FOR ABSOLUTE QUANTIFICATION WITH CRUDE PEPTIDE STANDARDS, WHOSE PURITY WILL BE COST- EFFECTIVELY ACCURATELY DETERMINED USING A COMBINED LANTHANIDE LABELING AND ICP-MS METHOD. WITH 96-WELL PLATE-BASED CSILAC PREPARATION AND WELL-CHARACTERIZED UIS, THE NEW SINGLE-CELL MS SYSTEM IS EXPECTED TO ALLOW FOR RAPID ACCURATE QUANTIFICATION OF A LARGE FRACTION OF HUMAN PROTEOME (~60%) IN SINGLE CELLS WITH ~120 SAMPLES PER DAY. WE ANTICIPATE THAT THE NEW MS SYSTEM WILL EVENTUALLY BECOME A CONVENIENT INDISPENSABLE TOOL NOT ONLY FOR QUANTITATIVE SINGLE-CELL PROTEOMICS BUT ALSO FOR ROUTINE ANALYSIS OF VERY SMALL SAMPLES (E.G., RARE CELLS). IN TURN, IT WILL MAKE SUBSTANTIAL CONTRIBUTIONS TO CURRENT BIOMEDICAL RESEARCH.

HUMAN CENTRIC APPROACH TO IMPROVE PIPELINE NON-DECTRUCTIVE EVALUATION (NDE) PERFORMANCE AND RELIABILITY

REDUCED NICOTINE CIGARETTES IN SMOKERS WITH AND WITHOUT ALCOHOL USE DISORDER

ONTOLOGY-DRIVEN GENERATION AND LINKING OF PATHWAY DIAGRAMS IN STROKE PATHOBIOLOGY

SYTEMS ANALYSIS OF NANOPARTICLE BIOCOMPATIBILITY

A USERFRIENDLY, NONINVASIVE NEURO-ORTHOSIS THAT RESTORES VOLITIONALLY CONTROLLED GRASP FUNCTIONS FOR SCI SURVIVORS WITH TETRAPLEGIA

MULTISCALE MODELING OF AEROSOL IMPACTS ON CLOUDS AND PRECIPITATIONAEROSOLS INFLUENCE CLOUDS ACROSS A

EVALUATION AND COMPARISON OF IMPACTS OF FLAVORED WATERPIPE TOBACCO AND ELECTRONIC WATERPIPE E-LIQUID FORMULATION VARIATIONS ON TOXICANT YIELDS AND PARTICLE SIZE DISTRIBUTION IN MAINSTREAM EMISSIONS - PROJECT SUMMARY WATERPIPE (WP) SMOKING HAS BECOME A POPULAR FORM OF TOBACCO USE IN THE US, ESPECIALLY AMONG YOUTH AND YOUNG ADULTS. THESE GROUPS ARE PARTICULARLY ATTRACTED TO FLAVORED WP TOBACCO (WPT). SWEET WPT FLAVORS ARE PREFERRED, WITH FRUIT FLAVORS IN PARTICULAR LEADING TO INITIATION AND CONTINUED WP USE, AS WELL AS THE MISPERCEPTION OF WP SMOKING AS LESS HARMFUL THAN CIGARETTE SMOKING. WPT SMOKING HAS BEEN LINKED TO MANY OF THE SAME ADVERSE HEALTH EFFECTS AS CIGARETTE SMOKING AND RELEASES MANY OF THE SAME HARMFUL AND POTENTIALLY HARMFUL CONSTITUENTS (HPHCS) AS CIGARETTES, AT 10-100 TIMES INCREASED LEVELS. THE POPULARITY OF FLAVORED WP SMOKING HAS EXPANDED IN RECENT YEARS TO FLAVORED TOBACCO-FREE ALTERNATIVES, INCLUDING ELECTRONIC WP (EWP). EWP REPLACES THE TRADITIONAL WP BOWL AND HEAT SOURCE WITH AN ELECTRONIC HEAD FILLED WITH FLAVORED, NICOTINE-CONTAINING LIQUID (E-LIQUID), TURNING THE WP INTO AN ELECTRONIC NICOTINE DELIVERY SYSTEM (ENDS). GIVEN THE RISING POPULARITY OF OTHER FLAVORED ENDS, EWP MAY POSE SIMILAR APPEAL AND UPTAKE CONCERNS. EWP MAY BE PERCEIVED AS A SAFE WP ALTERNATIVE, BUT IT HAS THE POTENTIAL TO RELEASE THE SAME HARMFUL EMISSIONS AS OTHER ENDS. YET NOTHING IS KNOWN ABOUT THE SAFETY OF EWP, OR IF IT OFFERS ANY HARM REDUCTIONS COMPARED TO WPT SMOKING. FLAVORED WP PRODUCTS MAY PLAY AN IMPORTANT ROLE IN THE DIRECT HARMS OF WP SMOKING. EWP E-LIQUIDS AND WPTS BOTH USE FLAVORANTS, SWEET HUMECTANTS (PROPYLENE GLYCOL AND GLYCEROL), AND SUGARS TO ENHANCE THEIR APPEAL. THESE INGREDIENTS IN CIGARETTES HAVE BEEN SHOWN TO FORM TOXIC ALDEHYDES AND FURANS DURING SMOKING. ENDS RESEARCH SHOWS THAT VARIATIONS IN E-LIQUID HUMECTANT CONTENT, AS WELL AS THE PRESENCE OF FLAVORINGS, CAN INCREASE ALDEHYDES EMISSIONS. FUNDAMENTAL KNOWLEDGE IS LACKING ON THE RANGE OF TOXICANTS EMISSIONS ACROSS FLAVORED WP PRODUCTS AND THE IMPACT OF VARIATIONS IN PRODUCT FORMULATIONS ON TOXIC EMISSIONS AND PARTICLE SIZE DISTRIBUTION, A CRITICAL PARAMETER IN THE DELIVERY OF TOXICANTS TO THE HUMAN RESPIRATORY SYSTEM. IN ORDER TO REGULATE WP SMOKING AND SET PRODUCT STANDARDS TO REDUCE HARMS AND PUBLIC HEALTH IMPACTS, IT IS IMPERATIVE THAT US FOOD AND DRUG ADMINISTRATION HAVE DATA TO UNDERSTAND THE IMPACT OF FLAVORED WP SMOKING ON EXPOSURE AND HOW EXPOSURES MAY DIFFER BETWEEN TRADITIONAL AND ALTERNATIVE WP SMOKING PLATFORMS. THIS STUDY WILL FILL THESE GAPS BY EVALUATING AND COMPARING THE IMPACT OF VARIATIONS IN FLAVOR PROFILES, HUMECTANTS AND SUGAR LEVELS, AND HEATING TEMPERATURES, IN A VARIETY OF COMMERCIALLY AVAILABLE WPTS AND EWP E-LIQUIDS ON YIELDS OF HPHCS AND OTHER TOXICANTS AS WELL AS PARTICLE SIZE DISTRIBUTION IN MAINSTREAM WP EMISSIONS. THIS WILL ALSO BE THE FIRST STUDY TO MEASURE TOXICANT EMISSIONS FROM EWP USE. THIS STUDY IS AN ESSENTIAL STEP IN PROVIDING ROBUST, FUNDAMENTAL INFORMATION ON WP PRODUCT FORMULATIONS AND TOXICANT EMISSIONS TO BETTER UNDERSTAND RELATIVE HARMS ASSOCIATED WITH FLAVORED WP SMOKING AND ESTABLISH A KNOWLEDGE BASE TO INFORM REGULATORY ACTIONS SURROUNDING WP PRODUCT STANDARDS.

HIGHLY SELECTIVE MACROBIOMOLECULAR ISOLATION, SOFT-LANDING AND CHARACTERIZATION USING STRUCTURES FOR LOSSLESS ION MANIPULATIONS - PROJECT SUMMARY/ABSTRACT (30 LINES) THIS PROJECT AIMS TO ADDRESS THE CURRENT GAP IN TECHNOLOGY FOR RAPID AND COMPREHENSIVE (MASS, STRUCTURE) PROFILING OF BIOMACROMOLECULES. WHILE HIGH RESOLUTION ION MOBILITY AND MASS SPECTROMETRY SEPARATIONS TECHNIQUES HAVE BEEN EXTENSIVELY DEVELOPED, THEIR APPLICATION HAS BEEN LARGELY LIMITED TO SMALL MOLECULES (M/Z < 2000). THE ABILITY TO ACCESS STRUCTURE AND MASS INFORMATION IN A HIGH-THROUGHPUT FASHION FOR MACROBIOMOLECULES IS AN ASPIRATIONAL GOAL IN MASS SPECTROMETRY. IN PURSUANCE OF THIS GOAL, WE WILL DEVELOP A HIGH-RESOLUTION ION MOBILITY CHEMICAL ANALYSIS DEVICE BASED ON STRUCTURES FOR LOSSLESS ION MANIPULATIONS, AND IN CONJUNCTION WITH MASS SPECTROMETRY OBTAIN HIGH-THROUGHPUT HIGH-RESOLUTION IMS/MS OF BIOMACROMOLECULES. THE STUDY OF THE SIGNIFICANT HETEROGENEITY IN LARGE BIOMOLECULAR SYSTEMS, I.E., MACROBIOMOLECULES, CRITICAL TO BIOLOGICAL RESEARCH WILL BE ENABLED BY THE DEVELOPMENT OF A NEW HIGH RESOLUTION, HIGH THROUGHPUT ANALYTICAL SYSTEM. THE SLIM PLATFORM, CURRENTLY ENABLED FOR ULTRA-HIGH RESOLUTION ION MOBILITY PROFILING (UP TO THE POINT OF SEPARATING ISOTOPOMERS AND ISOTOPOLOGUES) AND MANIPULATIONS OF SMALL MOLECULAR IONS (<3000 DALTONS) WILL BE OPTIMIZED TO EFFICIENTLY CONFINE, TRANSPORT AND SEPARATE MACROBIOMOLECULES. INITIAL OPTIMIZATION OF THE SLIM WILL BE DONE BY COUPLING WITH A TOF-MS SYSTEM. SLIM-TOF WILL BE USED TO PERFORM HIGH RESOLUTION IMS/MS OF ENSEMBLES OF MACROBIOMOLECULAR SPECIES (WITH AN UPPER MASS LIMIT OF ABOUT 20,000 DA DICTATED BY THE TOF). WE WILL USE SLIM-BASED IMS SEPARATIONS AND OTHER MANIPULATIONS TO REVEAL THE EXTENSIVE STRUCTURAL HETEROGENEITY OF MACROBIOMOLECULES. FURTHER, WE WILL PERFORM SIZE AND MASS SELECTIVE SOFT-LANDING OF MACROBIOMOLECULES USING THE DYNAMIC SWITCHING AND REROUTING (TO DEPOSITION SUBSTRATES) OF A SELECTIVE ION MOBILITY DISTRIBUTION IN THE SLIM. THE SOFT-LANDED SPECIES WILL BE CHARACTERIZED USING CRYO-EM AND COMPLIMENTARY IMAGING TECHNIQUES TO ELUCIDATE THE MORPHOLOGIES OF MACROBIOMOLECULES WITH SELECTED MOBILITIES OR COLLISION-CROSS-SECTIONS. THE COMBINATION OF ION MOBILITY INFORMATION AND IMAGING WILL PROVIDE A DETAILED STRUCTURAL CHARACTERIZATION OF MACROBIOMOLECULES.

ROLL YOUR OWN (RYO) CIGARETTES: PREVALENCE, SMOKING BEHAVIOR AND TOXIN EXPOSURE

PROTEOMIC INVESTIGATIONS OF ALCOHOLIC HEPATITIS

VALIDATION AND ADVANCED DEVELOPMENT OF EMERGING TECHNOLOGIES

HYBRID APPROACH TO REPURPOSE PLASTICS USING NOVEL ENGINEERED PROCESSES (HARNESS)

THE GOAL OF THIS PROJECT IS TO ACCELERATE THE ENTRANCE OF NEW ENVIRONMENTAL MONITORING TECHNOLOGIES INTO MARKETPLACE. TESTING IS PERFORMED TO VERIFY

INTERACTIVE INFORMATICS RESOURCE FOR RESEARCH-DRIVEN CANCER PROTEOMICS

CURRENT RISK ESTIMATES FOR MANNED SPACE FLIGHT ARE BASED PREDOMINANTLY ON HUMAN EPIDEMIOLOGY DATA FOLLOWING LOW LINEAR ENERGY (LET) RADIATION EXPOSUR

HIGH RESOLUTION HIGH THROUGHPUT PROTEOMICS PLATFORM FOR CANCER RESEARCH

SYSTEMATIC ASSESSMENT OF WELLBORE INTEGRITY FOR GEOLOGIC CARBON STORAGE PROJECTS USING REGULATORY

INTEGRATED WELLBORE INTEGRITY ANALYSIS PROGRAM FOR CO2 STORAGE APPLICATIONS

MODELING THE IMPACT OF SCIENCE POLICIES ON SCIENTIFIC WORKFORCE GROWTH

MAGNESIUM NMR OF DNA REPAIR PROTEINS

ENVIRONMENTAL TECHNOLOGY VERIFICATION PROVIDES OBJECTIVE QUALITY-ASSURED PERFORMANCE VERIFICATIONS OF TECHNOLOGIES ACROSS A BROAD SPECTRUM OF ENVIRO

HIGH THROUGHPUT SCREENS OF NOVEL RADIATION SENSITIZERS AND PROTECTORS

A STREAMLINED PLATFORM FOR PHOSPHOPROTEOME MAPPING OF HUMAN TISSUES - ABSTRACT RECENT TECHNOLOGICAL ADVANCES IN GENOMICS, TRANSCRIPTOMICS, AND PROTEOMICS ALLOW FOR RAPID GENERATION OF COMPREHENSIVE 3D-HUMAN TISSUE MAPS FOR BIOMOLECULES DNAS, RNAS, AND PROTEINS AT THE SINGLE-CELL RESOLUTION IN THE HUBMAP CONSORTIUM. HOWEVER, SINGLE-CELL TECHNOLOGIES FOR CHARACTERIZING FUNCTIONAL MODIFICATIONS ARE LAGGING FAR BEHIND BUT EQUALLY IMPORTANT AS THESE EXISTING OMICS TECHNOLOGIES. PROTEIN PHOSPHORYLATION IS ONE OF THE MOST IMPORTANT MODIFICATIONS AND OFTEN USED AS AN INDICATOR OF SIGNALING PATHWAY ACTIVATION (CELL FUNCTIONAL STATE). THE LACK OF HIGH-SPATIAL-RESOLUTION PHOSPHOPROTEOMIC CHARACTERIZATION OF HUMAN TISSUES IN THE HUBMAP CONSORTIUM REPRESENTS A SIGNIFICANT KNOWLEDGE GAP FOR ACHIEVING A MORE COMPLETE UNDERSTANDING OF HOW TISSUE HETEROGENEITY IMPACTS HUMAN HEALTH. THE OBJECTIVE OF THIS TTD APPLICATION IS TO ADDRESS THIS GAP BY DEVELOPING A CONVENIENT STREAMLINED PLATFORM FOR ENABLING AUTOMATED HIGH-RESOLUTION 3D-PHOSPHOPROTEOME MAPPING OF HUMAN TISSUES. THE PROJECT FEASIBILITY IS STRONGLY SUPPORTED BY OUR RECENT PROGRESS IN MANY ASPECTS OF TECHNOLOGY DEVELOPMENT: 1) CARRIER-ASSISTED SAMPLE PREPARATION (CASP) FOR BOTH GLOBAL AND TARGETED PROTEOMICS ANALYSIS OF 1-100 CELLS; 2) A BOOSTING TO AMPLIFY SIGNAL WITH ISOBARIC LABELING (BASIL) STRATEGY FOR HIGH-THROUGHPUT SINGLE- CELL PROTEOMICS; 3) BASIL/TIP-IMAC (IMMOBILIZED METAL AFFINITY CHROMATOGRAPHY) FOR RAPID PHOSPHOPROTEOMIC ANALYSIS OF SMALL NUMBERS OF CELLS; 4) ADVANCED LIQUID CHROMATOGRAPHY (LC) SEPARATION AND DISRUPTIVE MASS SPECTROMETRY (MS) TECHNOLOGIES (E.G., MULTI-EMITTER ARRAY TECHNOLOGY AND SUB-AMBIENT PRESSURE IONIZATION WITH NANOELECTROSPRAY (SPIN) SOURCE) FOR IMPROVING MS DETECTION SENSITIVITY. IN THE UG3 PHASE, AIM 1 WILL FOCUS ON THE DEVELOPMENT OF A STREAMLINED PLATFORM THROUGH 1) IMPROVING PHOSPHO-RECOVERY BY DEVELOPING AN IMPROVED CASP/ONLINE IMAC PLATFORM FOR AUTOMATED PROCESSING AND PHOSPHO-ENRICHMENT, AND 2) LEVERAGING MULTIPLE DISRUPTIVE TECHNOLOGIES DEVELOPED AT OUR GROUP WITH INTEGRATION OF A HIGH-EFFICIENCY MULTI-EMITTER SPIN (MSPIN) SOURCE AND BASIL-BASED SAMPLE MULTIPLEXING FOR SIGNIFICANTLY IMPROVING MS SENSITIVITY BY ~50-FOLD AND SAMPLE THROUGHPUT BY >20-FOLD. THE STREAMLINED PLATFORM WILL ALLOW FOR PRECISE QUANTIFICATION OF ~1,000 PHOSPHOSITES IN SINGLE CELLS AND ~7000 PHOSPHOSITES IN 10 CELLS WITH >1000 SAMPLES PER DAY. AIM 2 WILL DEMONSTRATE THE STREAMLINED PLATFORM FOR ENABLING 2D-PHOSPHOPROTEOME MAPPING OF MOUSE UTERINE TISSUES WHEN COMBINED WITH LASER CAPTURE MICRODISSECTION (LCM) AND STANDARD TUBE-BASED VOXEL COLLECTION. IN THE UH3 PHASE (AIM 3) WE WILL FURTHER OPTIMIZE THE STREAMLINED PLATFORM FOR AUTOMATED ROBUST PHOSPHOPROTEOMIC ANALYSIS OF LCM-DISSECTED HUMAN TISSUE SECTIONS. WE THEN WILL VALIDATE THE STREAMLINED PLATFORM FOR HIGH-RESOLUTION 3D-PHOSPHOPROTEOME MAPPING OF HUMAN BREAST AND UTERINE TISSUES AND OTHER HUMAN TISSUES FROM THE HUBMAP CONSORTIUM. AN EASY- TO-USE VISUALIZATION TOOL WILL BE DEVELOPED TO GENERATE 3D MAPS THAT CAN BE QUICKLY AND EASILY ACCESSIBLE BY THE RESEARCH COMMUNITY. WITH ITS ANTIBODY-FREE FEATURE, THE STREAMLINED PLATFORM CAN BE EQUALLY APPLICABLE TO ANY TYPES OF TISSUES. WE ENVISION THAT THE STREAMLINED PLATFORM WILL BECOME AN INDISPENSABLE TOOL FOR HIGH-RESOLUTION 3D-PHOSPHOPEOTEOME MAPPING OF HUMAN TISSUES IN THE HUBMAP CONSORTIUM AND EXTEND THE HUBMAP TOOLBOX FOR 3D-MAPPING OF FUNCTIONAL MODIFICATIONS. IN TURN, IT WILL MAKE SUBSTANTIAL CONTRIBUTIONS TO IMPROVE OUR UNDERSTANDING OF TISSUE BIOLOGY AND ACCELERATE THE MOVEMENT TOWARD PRECISION MEDICINE.

GEOMECHANICAL FRAMEWORK FOR SECURE CARBON DIOXIDE CO2 STORAGE IN FRANCTURED RESERVIORS AND CAPROCKS FOR SEDIMENTARY BASINS IN THE MIDWEST UNITED STAT

COMPUTATIONAL TOOLS FOR ILLUMINATING THE DARK MATTER OF THE HUMAN VIROME - PROJECT SUMMARY AS GREATER UNDERSTANDING OF THE IMPORTANT ROLE THAT THE HUMAN MICROBIOME PLAYS IN HUMAN HEALTH HAS UNFOLDED IT IS INCREASINGLY RECOGNIZED THAT THERE IS A VAST AND UNCHARTED GROUP OF VIRUSES THAT HAVE DIRECT AND IMPORTANT INFLUENCE ON THE COMPOSI�ON, DYNAMICS, AND FUNC�ON OF THESE MICROBIAL COMMUNI�ES, AND THUS ON THE HEALTH OF THE HUMAN HOST. METAGENOME SEQUENCING EFFORTS AND OTHER HIGH-THROUGHPUT METHODOLOGIES HAVE OPENED THE DOOR TO LARGE- SCALE CATALOGUING AND CHARACTERIZA�ON OF FREE-LIVING VIRUSES AND PROPHAGE, WHICH ARE RESIDENT IN THEIR BACTERIAL HOST GENOMES. HOWEVER, THE DIVERSITY AND LACK OF KNOWLEDGE ABOUT THESE VIRUSES HAMPERS OUR ABILITY TO UNDERSTAND THEIR POTEN�AL IMPACT. ILLUMINA�NG THE REGION OUTSIDE OF OUR CURRENT KNOWLEDGE, SO-CALLED ‘DARK MATER’, IS NECESSARY TO BE ABLE TO UNDERSTAND, MONITOR, CONTROL, AND U�LIZE VIRUS-COMMUNITY INTERAC�ONS TO PROMOTE HUMAN HEALTH. WE HYPOTHESIZE THAT APPLICA�ON OF ESTABLISHED AND NEWLY DEVELOPED PIPELINES USING THESE AND OTHER TOOLS WILL ALLOW VASTLY IMPROVED IDEN�FICA�ON AND CHARACTERIZA�ON OF VIRAL ELEMENTS THAT ARE IMPAC�NG HUMAN MICROBIOME DYNAMICS, AND THAT PROVIDING IMPROVED TOOLS FOR VISUALIZING THESE PREDIC�ONS AND THE RELA�ONSHIPS BETWEEN THEM WILL HAVE A BROAD IMPACT ON THE FIELD. TO ADDRESS THESE GAPS WE WILL DEVELOP ENHANCED METHODS FOR DETEC�ON OF VIRAL SEQUENCES USING GRAPH ASSEMBLIES, BUILD A SEQUENCE- AND STRUCTURE-BASED PIPELINE FOR CHARACTERIZA�ON OF AUXILIARY GENES CARRIED BY VIRUSES, AND PROVIDE NOVEL AND USEFUL WAYS OF VISUALIZING THIS COMPLEX INFORMA�ON TO ALLOW GREATER INSIGHT FROM RESEARCHERS IN THE FIELD.

PSYCHOSOCIAL SUPPORT TO HIV/AIDS AFFECTED CHILDREN IN ZIMBABWE

ADV.PROTEOMICS & METABOLOMICS:TYPE 2 DIABET & PRE-DIABET

SPATIALLY RESOLVED CHARACTERIZATION OF PROTEOFORMS FOR FUNCTIONAL PROTEOMICS - PROJECT SUMMARY/ABSTARCT DIFFERENTIATED CELLS HAVE DISTINCTIVE PATTERNS OF EPIGENETIC MARKS INCLUDING VARIOUS POST-TRANSLATIONAL MODIFICATIONS (PTMS) ON HISTONES THAT MAY WORK IN CONCERT TO CONTROL TRANSCRIPTIONAL PROGRAMS. SINCE EPIGENETIC MARKS ARE OFTEN ALTERED FOLLOWING EXPOSURE TO ENVIRONMENTAL TOXINS AND PLAY MULTIPLE ROLES IN DISEASE PATHOGENESIS, THE ABILITY TO MEASURE HISTONES IN A TISSUE AND CELL CONTEXT IS A MAJOR ANALYTICAL OBJECTIVE AND CHALLENGE. MASS SPECTROMETRY (MS) BASED PROTEOMICS IS A POWERFUL TOOL FOR CHARACTERIZING HISTONE ALTERATIONS IN MULTIPLEXED AND NON-TARGETED FASHION. HOWEVER, CONVENTIONAL BOTTOM-UP (I.E. PEPTIDE-LEVEL) MS CANNOT PROVIDE COMPLETE CHARACTERIZATION OF THE STOICHIOMETRY AND COMBINATIONS OF MULTIPLE PTMS, AND OTHER COMBINATORIAL SOURCES OF VARIATION, THAT COLLECTIVELY MAKE UP ANY SINGLE GENE'S SET OF PROTEOFORMS (I.E. FUNCTIONAL UNITS OF A PROTEOME). TOP-DOWN (I.E. PROTEOFORM-LEVEL) MS ADDRESSES THIS CHALLENGE BY OMITTING THE PROTEOLYSIS AND THUS ALLOWING ACCESS TO THE FUNCTIONAL PROTEOFORMS. HOWEVER, TOP-DOWN MS SUFFERS FROM LOW SENSITIVITY AND DYNAMIC RANGE DUE TO CHALLENGES IN SEPARATION AND DETECTION OF LARGE AND LOW-ABUNDANCE PROTEINS AND LABORIOUS PURIFICATION STEPS REQUIRED TO ACHIVE HIGH PROTEOME COVERAGE. THIS SEVERELY LIMITS OUR ABILITY TO ANALYZE SMALL SAMPLES AND EMPLOY TOP-DOWN MS TO GENERATE PROTEOFORM-AWARE IMAGES OF TISSUES REQUIRED FOR A DEEPER UNDERSTANDING OF HUMAN ORGAN FUNCTIONING IN HEALTH AND DISEASE. WE HAVE RECENTLY DEVELOPED NANODROPLET SAMPLE PREPARATION (NANOPOTS) FOR HIGHLY SENSITIVE BOTTOM-UP PROTEOMICS AND EXTENDED THIS APPROACH TO TISSUE IMAGING WITH 100 ΜM SPATIAL RESOLUTION. HEREIN, WE PROPOSE TO DEVELOP AND DEPLOY NANOPOTS-BASED TOP-DOWN MS TO ENABLE CHARACTERIZATION OF PROTEOFORMS IN TISSUE SECTIONS WITH NEAR SINGLE CELL RESOLUTION. TO INCREASE THE RESOLUTION FROM THOUSANDS OF CELLS TO NEAR SINGLE CELL, WE WILL EMPLOY ADVANCED MS IMAGING (MSI) APPROACHES. MSI DATA WILL BE CROSS-REFERENCED WITH GLOBAL PROTEOMICS DATA OBTAINED VIA MICROSCALE TOP-DOWN MS OF MICRODISSECTED TISSUE REGIONS. THE UG3 PHASE EFFORTS WILL BE FOCUSED ON HISTONES AND KIDNEY AS A DEVELOPMENT PLATFORM AND LEVERAGE A UNIQUE COMBINATION OF MICROSCALE TOP-DOWN LCMS, MSI AND NOVEL IMAGE PROCESSING AND VISUALIZATION TOOLS. IN THE UH3 PHASE, WE WILL CONSTRUCT COMPREHENSIVE PROTEOFORM-SPECIFIC MAPS OF MULTIPLE TISSUE TYPES AND FACILITATE MULTIMODAL MOLECULAR MAPPING OF SPECIFIC FUNCTIONAL UNITS OF THE KIDNEY BY LEVERAGING THE HUBMAP CONSORTIUM ONGOING EFFORTS. SUCCESSFUL COMPLETION OF THIS RESEARCH WILL ALLOW FOR COMPREHENSIVE CHARACTERIZATION OF THE FULL SPECTRUM OF PROTEOFORMS IN TISSUES AND CELLS THUS ADDRESSING AN IMPORTANT AND UNDER- STUDIED AREA OF BIOLOGY AND CRITICAL GAP IN HUBMAP EFFORTS.

THE PI WILL EVALUATE CELLULAR IN VITRO ASSAY SYSTEMS OF THE RAINBOW TROUT PITUITARY, LIVER AND OVARY FOR HIGH-THROUGHPUT SCREENING (HTS) OF ENVIRONM

HIGH-THROUGHPUT EVALUATION OF BREAST CANCER MARKERS

AWARD DE-FE0029264 TITLED INTEGRATED MID-CONTINENT STACKED CARBON STORAGE HUB.

EFFECT OF WATERPIPE TOBACCO INGREDIENTS ON HUMAN PUFFING, EXPOSURES AND APPEAL

AIR QUALITY & CONGESTION MITIGATION

NEW AWARD DE-FE0029276 PROJECT TITLED: ''NORTHERN MICHIGAN BASIN CARBONSAFE INTEGRATED PRE-FEASIBILITY PROJECT.''

DE-FE0029466 PROJECT TITLE: CAB-CS: CENTRAL APPALACHIAN BASIN CARBONSAFE INTEGRATED PRE-FEASIBILITY PROJECT

"THIS PROJECT WILL FOCUS ON FOUR MAIN STEPS TO REDUCE BLACK CARBON EMISSIONS FROM DIESEL SOURCES IN THE RUSSIAN ARCTIC: 1)

CATALYTIC CONVERSION OF BIOMASS TO FUELS AND CHEMICALS USING IONIC LIQUIDS

STATISTICAL METHODOLOGY FOR CHARACTERIZATION OF MACROMOLECULAR SIMILARITY

TYING DISTINCT NANOPARTICLE PROPERTIES TO CELLULAR INTERACTIONS, FATE AND RESPONS

DEVELOPMENT OF LEWY BODIES BIOFLUID SIGNATURES BY TARGETED PROTEOMICS

THE PURPOSE OF THIS PROJECT IS TO IMPROVE URBAN AIR QUALITY MANAGEMENT IN CENTRAL AMERICA AND THE DOMINICAN REPUBLIC THROUGH ENHANCED KNOWLEDGE OF A

SPATIALLY-RESOLVED PROTEOME MAPPING OF SENESCENT CELLS AND THEIR TISSUE MICROENVIRONMENT AT SINGLE-CELL RESOLUTION - PROJECT SUMMARY/ABSTRACT CELLULAR SENESCENCE IS A PERMANENT STATE OF CELL CYCLE ARREST INDUCED BY MANY DIFFERENT STRESSES. ALTHOUGH SENESCENT CELLS (SNCS) HAVE BEEN DEMONSTRATED WITH BENEFICIAL ROLES IN NORMAL PHYSIOLOGICAL PROCESSES, THEY ARE INCREASINGLY RECOGNIZED AS THE KEY DETERMINANTS OF MANY AGING-RELATED DISEASES, SUCH AS CANCER, OSTEOARTHRITIS, AND TYPE 2 DIABETES. THE SNCS AND SENESCENCE-ASSOCIATED SECRETORY PHENOTYPE (SASP) ARE FOUND TO BE HIGHLY HETEROGENEOUS AND VARY IN DIFFERENT TYPES OF CELLS AND TISSUE REGIONS. CURRENTLY, THERE ARE NO “UNIVERSAL” BIOMARKERS FOR IDENTIFYING THE SNCS IN VIVO. THE FIRST STEP TOWARDS ADVANCING OUR UNDERSTANDING OF CELLULAR SENESCENCE AND DEVELOPING SNC-TARGETING THERAPY APPROACHES IS TO COMPREHENSIVELY CHARACTERIZE CELLULAR SENESCENCE IN VARIOUS HUMAN TISSUES. MASS SPECTROMETRY (MS)-BASED SPATIAL PROTEOMICS CAN PROVIDE DIRECT INSIGHTS INTO CELLULAR HETEROGENEITY AND REVEAL NOVEL PROTEIN MARKERS. HOWEVER, CURRENT SPATIAL PROTEOMICS TECHNOLOGIES ARE LIMITED BY THEIR POOR SPATIAL RESOLUTION AND LOW ANALYSIS THROUGHPUT. THE OVERALL OBJECTIVE OF THIS PROJECT IS TO SIGNIFICANTLY ADVANCE OUR MICROFLUIDICS-BASED SPATIAL PROTEOMICS PLATFORM, TERMED LASER CAPTURE MICRODISSECTION COUPLED WITH NANODROPLET PROCESSING IN ONE-POT FOR TRACE SAMPLES (LCM-NANOPOTS), AND APPLY THIS TECHNOLOGY TO MAP SNCS AND THEIR SASP IN DIFFERENT MOUSE AND HUMAN TISSUES. IN THE UG3 PHASE, WE WILL ESTABLISH A HIGH-THROUGHPUT AND ROBUST SINGLE-CELL ISOLATION SYSTEM AND COUPLE IT WITH NANOPOTS-MS. WE WILL MODIFY THE ZEISS LCM SYSTEM TO ENABLE RELIABLE SINGLE-CELL ISOLATION AND COLLECTION BY DESIGNING AND ASSEMBLING A ROBOT-ADDRESSABLE CAPILLARY SAMPLING PROBE. NEXT, WE WILL DEPLOY THE SPATIAL SINGLE-CELL PROTEOMICS PLATFORM FOR MAPPING OF SNCS AND THEIR SASP IN MOUSE SKIN TISSUE. WE WILL DEVELOP A STREAMLINED WORKFLOW TO IDENTIFY SNCS FROM FASST MOUSE SKINS. IMMUNOHISTOCHEMISTRY OR IMMUNOFLUORESCENCE WILL BE USED TO VALIDATE NOVEL PROTEIN MARKER CANDIDATES. IN THE UH3 PHASE, WE WILL SIGNIFICANTLY ENHANCE PROTEOME COVERAGE AND ANALYSIS THROUGHPUT OF THE NANOPOTS-LC-MS PLATFORM. WE AIM TO ACHIEVE A THROUGHPUT OF >300 SAMPLES/DAY AND A PROTEOME COVERAGE OF >1500 PROTEINS. THE NANOPOTS SAMPLE PREPARATION WILL BE OPTIMIZED FOR FORMALIN-FIXED PARAFFIN- EMBEDDED (FFPE) TISSUES FOR BROAD APPLICATIONS OF SPATIAL PROTEOMICS TECHNOLOGY. NEXT, WE WILL DEMONSTRATE THE IMPROVED PLATFORM IN DIFFERENT TISSUE TYPES, INCLUDING MOUSE LIVER, SKIN DRAINING LYMPH NODES, AS WELL AS HUMAN LIVER, BREAST, AND LUNG TISSUES. WE WILL ESTABLISH COLLABORATIONS WITH DIFFERENT TMCS TO CHARACTERIZE SNCS AND SASP USING SPATIAL PROTEOMICS IN VARIOUS HUMAN TISSUES AND CONTRIBUTE TO MULTIOMICS MAPPING OF THE TISSUES. STATEMENT OF IMPACT: THE CAPABILITY TO GENERATE UNBIASED AND COMPREHENSIVE PROTEOME MAPS AT SINGLE-CELL RESOLUTION WILL ENABLE THE DISCOVERY OF SNC PROTEIN MARKERS ACROSS DIFFERENT CELL TYPES AND ORGANS, AND ADVANCE OUR UNDERSTANDING OF THE IMPACT OF SNCS ON TISSUE MICROENVIRONMENT.

VISUAL ANALYTICS SOFTWARE ENVIRONMENT FOR PROTEOMICS DATA INTEGRATION

FAULT SENSING IN OPERATING BATTERIES

VALIDATION OF NOVEL PEPTIDE/PROTEIN MARKERS FOR DIAGNOSIS OF TYPE 1 DIABETES

DEVELOPMENT AND VALIDATION OF AN ACID MINE DRAINAGE WATER TREATMENT PROCESS

AEROSOL EFFECTS ON COLD SEASON OROGRAPHIC PRECIPITATION AND WATER RESOURCES

SYNTHETIC BIOLOGY DRIVEN APPROACH TO REPURPOSE POLYAMIDES (STORM)

TOWARDS AN OPERATIONAL FORECAST SYSTEM FOR THE SALISH SEA ??? REFINEMENT, IMPROVEMENT, AND TESTING FOR TRANSITIONING OF THE EXISTING SALISH SEA MODEL TO NATIONAL OCEAN SERVICE (NOS)

MASS SPECTROMETRIC TISSUE IMAGING OF SUGARS, GLYCANS, AND GLYCOCONJUGATES - PROJECT SUMMARY/ABSTRACT THE GLYCOME DESCRIBES THE COMPLETE REPERTOIRE OF CELL CARBOHYDRATES THAT ARE EITHER FREE OR COVALENTLY LINKED TO LIPID OR PROTEIN MOLECULES, HAVING THE SPAN OF BIOLOGICAL ROLES FROM THOSE THAT ARE SUBTLE TO THOSE THAT ARE CRUCIAL FOR AN ORGANISM'S DEVELOPMENT, FUNCTION, OR SURVIVAL. BECAUSE THOSE MOLECULES ARE NOT ENCODED DIRECTLY IN THE GENOME, ONE CANNOT ACCURATELY PREDICT THE PRECISE STRUCTURES OF GLYCANS ELABORATED BY A GIVEN CELL TYPE. FURTHERMORE, SMALL CHANGES IN ENVIRONMENTAL CUES CAN CAUSE DRAMATIC CHANGES IN GLYCANS PRODUCED BY A GIVEN CELL, WHICH CAN OFTEN LEAD TO PATHOLOGY, AND AS SUCH, DEVELOPING CAPABILITIES FOR IDENTIFYING THOSE CHANGES AT THE CELL-SPECIFIC LEVEL IS NECESSARY. HISTORICALLY, NUCLEAR MAGNETIC RESONANCE (NMR) AND MASS SPECTROMETRY (MS) HAVE BEEN USED FOR GLYCOME STRUCTURAL ELUCIDATION, BUT THOSE TECHNIQUES HAVE LIMITED CAPABILITY TO CAPTURE CHEMICAL DIFFERENCES AT THE SPATIAL LEVEL, WHILE LECTINS AND OTHER GLYCAN-LABELING IMAGING APPROACHES PROVIDE ONLY LIMITED INFORMATION ON CARBOHYDRATES STRUCTURES. OVER THE LAST DECADE, MASS SPECTROMETRY IMAGING (MSI) EVOLVED AS A POWERFUL TOOL TO LINK CHEMICAL STRUCTURES WITH TISSUE LOCALIZATION, AND IT HAS BEEN SUCCESSFULLY USED TO REVEAL DIFFERENCES IN METABOLITES, LIPIDS, AND XENOBIOTICS ACROSS NUMEROUS HUMAN TISSUES, CELL TYPES, AND CELL STATES. HOWEVER, MSI STILL HASN’T SHOWN ITS FULL POTENTIAL IN GLYCOME IMAGING DUE TO CARBOHYDRATES' POOR IONIZABILITY, COMPLEX CHEMISTRY, AND AMBIGUOUS MOLECULAR ANNOTATION. I HAVE SUCCESSFULLY SOLVED SOME OF THOSE ISSUES THROUGHOUT MY CAREER, ENABLING A BETTER UNDERSTANDING OF THE GLYCOME-PHENOTYPE RELATIONSHIP. HEREIN, I PROPOSE TO DEVELOP AND ADVANCE MSI TOOLS THAT WILL ENABLE MORE ACCURATE AND COMPREHENSIVE CHEMICAL CHARACTERIZATION OF THE GLYCOME AT TISSUE FUNCTIONAL UNIT AND CELLULAR RESOLUTIONS. I WILL DEVELOP VARIOUS WORKFLOWS, MODIFY AND OPTIMIZE EXISTING MSI APPROACHES, AND, IN COMBINATION WITH AUXILIARY TOOLS, MAP SOLUBLE SUGARS, GLYCOLIPIDS, PROTEOGLYCANS, POLYSACCHARIDES, AND GLYCOPROTEINS FROM THE HUMAN TISSUES. MORE SPECIFICALLY, IN COMBINATION WITH HIGH-RESOLVING MASS SPECTROMETERS, I WILL UTILIZE VARIOUS IONIZATION AND POST-IONIZATION SOURCES, ORTHOGONAL ANALYSES, ON-TISSUE CHEMICAL DERIVATIZATION, IN-TISSUE DIGESTION, AND GLYCAN ENRICHMENT STRATEGIES TO OVERCOME CURRENT LIMITATIONS IN GLYCOME IMAGING. SUCCESSFUL COMPLETION OF THIS RESEARCH WILL CREATE A ROBUST, HIGH- THROUGHPUT CAPABILITY FOR GLYCOME IMAGING THAT WILL ENABLE AN UNDERSTANDING OF HOW, AT THE CELL-SPECIFIC LEVEL, GLYCOME PROCESSING AND GLYCOME REDISTRIBUTION MEDIATE PHYSIOLOGICAL AND PATHOLOGICAL PROCESSES, THUS ADDRESSING A CRITICAL GAP IN THE GLYCOSCIENCES AREA OF THE BIOCHEMISTRY AND BIO-RELATED CHEMISTRY BRANCH OF NIGMS.

NEXT-GENERATION SEQUENCING (NGS) FEASIBILITY AND GUIDANCE STUDY FOR FORENSIC DNA.

MIXTURE MODELING: PESTICIDE DRUG INTERACTIONS

SIMPLIFIED PREDICTIVE MODELS FOR CO2 SEQUESTRATION PERFORMANCE ASSESSMENT

TAS::89 0336::TAS RECOVERY CASCADE REVERSE OSMOSIS AND THE ABSORPTION OSMOSIS CYCLE MORE THAN 90% OF COOLING IS PROVIDED BY VAPOR COMPRESSION

ACOUSTIC EMISSIONS SENSING FOR TRACING CARBON DIOXIDE MOVEMENT IN CAPROCK OF A CARBON CAPTURE UTILIZATION AND STORAGE SYSTEM (CCUS) DE-FE0032062 BATTELLE MEMORIAL INSTITUTE

SMOKERS AND PREPS: MEASUREMENT OF INHALED AND EXHALED TOBACCO SMOKE PARTICULATE

A STREAMLINED PLATFORM FOR PHOSPHOPROTEOME MAPPING OF HUMAN TISSUES

THIS RESEARCH WILL DEVELOP A COMPUTATIONAL FRAMEWORK FOR CALCULATING EXPOSURE AND TARGET TISSUE DOSE FOR ESTROGEN (ER) AND ANDROGEN (AR) RECEPTOR BI

DE-FE0031795, BATTELLE MEMORIAL INSTITUTE, A NOVEL PROCESS FOR CONVERTING COAL TO HIGH-VALUE POLYURETHANE PRODUCTS

DEVELOPMENT OF A NANOLITER SLOW-MAS NMR METABOLOMICS PROBE

RECOVERY OF RARE EARTH ELEMENTS (REES) FROM COAL ASH WITH A CLOSED LOOP LEACHING PROCESS

ACCELERATED DEVELOPMENT OF NONVIRAL VEHICLES DELIVERING MRNA TO MICROGLIA EXPRESSING BASE EDITORS FOR MUTATION-INDEPENDENT TREATMENT OF ALS

AN ULTRASENSITIVE TARGETED MASS SPECTROMETRY SYSTEM FOR PROTEOMICS ANALYSIS OF SINGLE CELLS

RDTE FACILITY - PACIFIC NORTHWEST BALLAST TREATMENT CENTER

PSEUDOMONAS AERUGINOSA OUTER MEMBRANE PROTEIN MODELING

PHONE-BASED POSTPARTUM CONTINUING CARE: SMOKING CESSATION BEGINNING IN PREGNANCY

DE-FE0031529: RECOVERY OF HIGH PURITY RARE EARTH ELEMENTS FROM COAL ASH VIA A NOVEL ELECTROWINNING PROCESS

IMMIGRATION EFFECTS ON SUBSTANCE ABUSE, MENTAL HEALTH AND TREATMENT GAPS

21-DSI-21-0027 GLOBALLY-DERIVED MEASURES OF STRUCTURE INFORMED BY ECOLOGICAL THEORY AND OBSERVATION

BIOINFORMATICS FOR PROTEIN MICROARRAYS

THE BIOCHEMISTRY PHYSIOLOGY AND ORIENTATION OF FOLIAGE IS A KEY DRIVER OF PRODUCTIVITY IN FORESTS AND HAS SPAWNED MULTIPLE LEAF TRAIT REMOTE SENSING STUDIES AS A MEANS OF LEAF-TO-ECOSYSTEM SCALING.

A HYBRID IMS-MS PLATFORM FOR ULTRASENSITIVE AND HIGH RESOLUTION GLYCAN ANALYSIS

THIS PROJECT WILL DEVELOP AND DEMONSTRATE AN AUTOMATED SYSTEM APPROACH FOR LARGE VOLUME CONCENTRATION, PURIFICATION, AND QUANTITATIVE DETECTION OF

THE IMPACT OF ORGANIC MATTER AND BLACK CARBON EMISSIONS ON REGIONAL VARIATIONS IN AEROSOL RADIATIVE FORCING OVER CALIFORNIA

HUMAN EXPOSURE MODELING FOR PBDE DERIVATIVES

HIGH-RESOLUTION FLEXIBLE MOBILITY ANALYZER FOR POINT-OF-CARE DIAGNOSTICS - PROJECT SUMMARY THIS PROJECT AIMS TO ADDRESS THE CURRENT GAP IN TECHNOLOGY FOR RAPID LIPIDS PROFILING. A POINT-OF-CARE TECHNOLOGY THAT PROVIDES QUICK DETECTION WILL IMPACT HEALTHCARE MANAGEMENT BY LEVERAGING PATIENT’S PROACTIVE PARTICIPATION. IN PURSUANCE OF THIS GOAL, WE WILL DEVELOP AN ION MOBILITY CHEMICAL ANALYSIS TECHNOLOGY, WHICH PROVIDES CHEMICAL INFORMATION WITH MOLECULAR LEVEL SPECIFICITY, FOR DISEASE DIAGNOSTICS AND MONITORING AND IDENTIFICATION OF PATHOGENS. THE PROJECT WILL FOCUS ON A PROOF-OF- CONCEPT TECHNOLOGY FOR A PORTABLE MOLECULAR ANALYZER DEVICE THAT CAN BE UTILIZED TO ANALYZE BREATH, SALIVA, BLOOD PRICKS IN ITS MATURE STAGE FOR MARKERS OF DISEASE. THE NEW DEVICE WILL BE DESIGNED BASED ON EXTENSIVE ION TRAJECTORY SIMULATIONS THAT WILL PROVIDE THE GEOMETRICAL AS WELL AS OPTIMAL OPERATING PARAMETERS. OPTIMAL DESIGNS WILL BE USED TO BUILD PROTOTYPES THAT WILL BE EVALUATED IN TERMS OF SENSITIVITY AND SELECTIVITY FOR DETECTING TARGETED MOLECULES TO DEMONSTRATE A WORKING PROTOTYPE IN CONJUNCTION WITH A MASS SPECTROMETER.

ALCOHOL USE TRAJECTORIES AMONG OLDER ADULTS

SPATIALLY RESOLVED CHARACTERIZATION OF PROTEOFORMS FOR FUNCTIONAL PROTEOMICS

PAN-OMIC CHARACTERIZATION OF THE MOLECULAR DETERMINANTS OF UTERINE RECEPTIVITY

THE PROPOSAL LEVERAGES A NOVEL POLYMERIC/PROTEIN NANOPARTICLES (PNP) PLATFORM THAT WILL BE USED TO DELIVER AN EPISOMAL DNA, WHICH CONSISTS OF AN EPISOMAL CONSTRUCT WITH A TETRACYCLINE INDUCER-PROMOTER (TRE). SYNTHESIS OF PNPS THAT TARGET THE NEURON WILL BE GUIDED BY A NOVEL AI/ML MODEL THAT OPTIMIZES PNP SYNTHESIS BASED ON THE TARGET ORGAN AND/OR PARTICLE SIZES NEEDED TO DIFFUSE ACROSS NEURONAL TISSUES. NOT ONLY IS THE PLATFORM INNOVATIVE, BUT THE AI/ML MODEL AND PATENTED METHOD FOR SYNTHESIS OF PNPS IS UNIQUE TO THE OFFEROR. THE USE OF PNPS AS A DRUG DELIVERY SYSTEM CAN BE APPLIED TO A WIDE RANGE OF APPLICATIONS INCLUDING DELIVERY OF THERAPEUTICS TO TARGET ORGANS WHEN THE WARFIGHTER IS EXPOSED TO VARIOUS BIOTHREATS INCLUDING VIRUSES, TOXINS, CHEMICAL THREAT AGENTS, ETC. THE PROPOSED PLATFORM HAS STRONG PROOF-OF-CONCEPT DATA WITH PNPS SHOWING A STRONG SAFETY PROFILE AND HAVE BEEN USED IN CLINICAL TRIALS.

THE PROPOSED PROJECT SEEKS TO DEVELOP THE PRE-FRONT END ENGINEERING DESIGN (PRE-FEED) OF AN INTERMODAL TRANSPORT HUB.

DISCOVERY OF PHOSGENE AND CHLORINE GAS MODES OF ACTION AND THERAPEUTIC TARGETS USING CHEMOPROTEOMIC PROFILING STRATEGIES - PROJECT SUMMARY: PHOSGENE AND CHLORINE ARE TWO TOXIC GASES PRODUCED ON LARGE INDUSTRIAL SCALES THAT POSE OCCUPATIONAL HAZARDS AND CHEMICAL THREATS TO THE PUBLIC AND MILITARY. BOTH TOXICANTS MODIFY PROTEINS IN VARIOUS WAYS AND INDUCE OXIDATIVE STRESS IN THE LUNG WHICH PERTURB CRITICAL FUNCTIONS AND PATHWAYS. HOWEVER, THE PRECISE NATURE AND SITES OF THESE MODIFICATIONS IN THE LUNG PROTEOME HAVE NOT BEEN IDENTIFIED, AND THE POTENTIAL CHEMICAL DIVERSITY OF THESE MODIFICATIONS POSES AN ANALYTICAL CHALLENGE TO UNRAVELING THE MOLECULAR MECHANISMS BY WHICH CHLORINE AND PHOSGENE INDUCE ACUTE LUNG INJURY. THIS LACK OF BIOMOLECULAR CHARACTERIZATION OF PHOSGENE- AND CHLORINE-INDUCED MODIFICATION OF PROTEIN TARGETS HAS CONSEQUENTLY HINDERED OUR ABILITY TO DEVELOP EFFECTIVE COUNTERMEASURES; THERE ARE CURRENTLY NO APPROVED THERAPEUTICS FOR TREATING PHOSGENE OR CHLORINE GAS EXPOSURES. WE PROPOSE TO USE CHEMOPROTEOMIC PROFILING—A SUBSET OF MASS SPECTROMETRY-BASED PROTEOMICS THAT CAN DETECT THE SITES AND TYPES OF DISTINCT CHEMICAL MODIFICATIONS TO PROTEINS—TO COMPREHENSIVELY IDENTIFY SPECIFIC PROTEINS IN THE LUNG THAT HAVE BEEN CHEMICALLY ALTERED BY PHOSGENE AND CHLORINE AND PERFORM PATHWAY ANALYSIS TO IDENTIFY PROTEIN CANDIDATES FOR FUTURE TARGETED COUNTERMEASURE DEVELOPMENT. THE SPECIFIC AIMS OF THIS PROPOSAL ARE: AIM 1: DYNAMIC REDOX PROFILING TO IDENTIFY THE TEMPORAL PROTEIN CYSTEINE OXIDATION EVENTS AND GLOBAL PROTEOME CHANGES FOLLOWING GASEOUS TOXICANT EXPOSURE AIM 2: MAPPING PHOSGENE- AND CHLORINE-INDUCED PROTEIN MODIFICATIONS IN THE LUNG USING ELECTROPHILIC CHEMICAL PROBES AIM 3: DATA INTEGRATION AND NETWORK ANALYSIS TO IDENTIFY SHARED AND UNIQUE MOLECULAR TARGETS OF PHOSGENE AND CHLORINE FOR THERAPEUTIC DEVELOPMENT

NOVEL CHELATORS FOR HIGHLY EFFICIENT REMOVAL OF TOXIC HEAVY METALS IN HUMANS

NATURAL PRODUCTS MAGNETIC RESONANCE DATABASE (NP-MRD) PHASE II - PROJECT SUMMARY/ABSTRACT SINCE ITS LAUNCH IN 2021, THE NATURAL PRODUCTS MAGNETIC RESONANCE DATABASE (NP-MRD, HTTPS://NP-MRD.ORG) HAS BECOME THE LARGEST OPEN REPOSITORY OF NMR DATA ON NATURAL PRODUCTS (NPS) AS WELL AS THE LARGEST COLLECTION OF GENERAL INFORMATION (NOMENCLATURE, STRUCTURE, BIOLOGY, CHEMISTRY) ABOUT NPS IN THE WORLD. THE NP-MRD CONTAINS SUBSTANTIAL AMOUNTS OF DIFFERENT TYPES OF NMR DATA INCLUDING RAW NMR DATA (FREE INDUCTION DECAYS OR FIDS), PREDICTED NMR DATA AND LITERATURE-DERIVED NMR INFORMATION (CHEMICAL SHIFT ASSIGNMENTS, COUPLING CONSTANTS). THE NMR DATA IN THE NP-MRD INCLUDES 15,000 SETS OF EXPERIMENTAL NMR SPECTRA (FOR 3200 NPS), 411,000 SIMULATED NMR SPECTRA (FOR 21,000 NPS) OBTAINED FROM LITERATURE-DERIVED NMR ASSIGNMENTS, AND 5.1 MILLION PREDICTED NMR SPECTRA (FOR ALL 282,000 NPS). MUCH OF THE RAW NMR DATA IN THE NP-MRD IS THERE DUE TO A CONCERTED EFFORT BY NP-MRD, TOGETHER WITH THE JOURNAL OF NATURAL PRODUCTS (JNP), TO ENCOURAGE RAW DATA DEPOSITION OF NMR DATA USED TO SUPPORT NOVEL STRUCTURE ELUCIDATION. FOR THE SECOND PHASE OF THE NP-MRD (2025- 2030) WE WILL BUILD ON THE MOMENTUM CREATED IN THE FIRST PHASE. SPECIFICALLY, WE WILL OPTIMIZE CURRENT OPERATIONS AND CONTINUE ONGOING EXPANSION OF BOTH THE DATABASE CONTENT AND UTILITY. A MAJOR EMPHASIS WILL BE ON STREAMLINING NP-MRD OPERATIONS SUCH THAT MOST OF ITS OPERATIONS WILL REQUIRE LITTLE HUMAN INTERVENTION. FOR EXAMPLE, RAW DATA DEPOSITION FORMERLY REQUIRED TWO NP-MRD STAFF IN TWO DIFFERENT LOCATIONS TO INTERACT WITH THE DEPOSITED DATA, AND WITH THE DEPOSITOR. TODAY, RAW DATA DEPOSITION GOES AUTOMATICALLY INTO A PARSER, A SET OF QUALITY CHECKS AND STRAIGHT INTO THE NP-MRD REPOSITORY WITH NO HUMAN INTERVENTION UNLESS (RARE) PROBLEMS OCCUR WITH THE DATA. OTHER FUNCTIONS BEING STREAMLINED, INCLUDE CENTRALIZED PROCESSES TO QUERY, ENTER AND ASSESS NP- MRD DATA, BETTER PROCESSES TO ANNOTATE NP STRUCTURES, TOOLS TO MORE EFFICIENTLY GATHER BIOLOGICAL, MEDICINAL, STRUCTURAL, CHEMICAL SHIFT AND ASSIGNMENT DATA FROM THE PUBLISHED LITERATURE, AS WELL AS WORKFLOWS TO CORRECT ENTRIES, REMOVE DUPLICATES AND IMPROVE ACCURACY. IN TERMS OF DATA CONTENT AND UTILITY EXPANSION, MAJOR EFFORTS WILL BE UNDERTAKEN TO INCREASE USER DEPOSITION RATES, SUPPORT THE DEPOSITION, INTEGRATION AND FEDERATION OF MASS SPECTROMETRY (MS) DATA FOR NPS INTO THE NP-MRD, IMPLEMENT FASTER, MORE “INTELLIGENT” NMR, MULTI-SPECTRAL (NMR+MS+CCS+RT) AND MULTI-DATABASE (GNPS, MONA, MASSBANK, HMDB, FOODB) SEARCHES, SUPPORT MORE ACCURATE CHEMICAL SHIFT, J-COUPLING AND OTHER KINDS OF “OBSERVABLES” PREDICTION, AND CREATE NEW TOOLS TO SUPPORT AUTOMATED COMPUTER-AIDED NP STRUCTURE ELUCIDATION (CASE) AND DEREPLICATION. THESE STREAMLINING, OPTIMIZATION AND DATABASE EXPANSION EFFORTS ARE BEING DONE TO ENSURE LONG-TERM SUSTAINABILITY OF THE NP-MRD BY MAKING OPERATIONS CHEAPER, MORE AUTOMATED, MORE USEFUL AND MORE VALUABLE TO THE NP COMMUNITY. OUTREACH TO OTHER NP JOURNALS AND TO THE NP COMMUNITY WILL BE FURTHER EXPANDED, WITH THE EXPECTATION THAT THESE EFFORTS WILL TRIPLE THE DATA DEPOSITION RATE TO THE NP-MRD BY 2030, INCREASE COMMUNITY BUY-IN, INCREASE GRANT OR CO-FUNDING SUPPORT, ATTRACT PAYING SUBSCRIBERS AND ENSURE LONG-TERM SUSTAINABILITY OF THE NP-MRD.

A STATE-OF-ART NMR TECHNIQUE TO INVESTIGATE BIOLOGICALS EFFECTS OF ELECTRONIC NICOTINE DELIVERY SYSTEMS

AUTOMATED PROTEOGENOMIC ANNOTATION FOR PROKARYOTIC GENOMES

HIGH THROUGHPUT LIPIDOMIC PROFILING WITH HIGH STRUCTURAL SPECIFICITY FOR PHENOTYPIC SCREENING - PROJECT ABSTRACT LIPIDS ARE A DIVERSE CLASS OF BIOMOLECULES THAT PLAY PIVOTAL ROLES IN VARIOUS CELLULAR PROCESSES AND HAVE BEEN IMPLICATED IN THE PATHOGENESIS OF DISEASES SUCH AS DIABETES, ALZHEIMER'S, PARKINSON'S, AND VARIOUS CANCERS. UNDERSTANDING LIPID STRUCTURES AND FUNCTIONS IS CRUCIAL FOR UNRAVELING THEIR ROLES IN COMPLEX BIOLOGICAL SYSTEMS AND DISEASES. UNAMBIGUOUS IDENTIFICATION OF LIPIDS, PARTICULARLY WITH HIGH-LEVEL STRUCTURAL DETAILS AND SEPARATION OF LIPID ISOMERS, HAS BEEN AN ANALYTICAL CHALLENGE. HOWEVER, SUCH KNOWLEDGE IS ESSENTIAL FOR OBTAINING A FULL UNDERSTANDING OF LIPID FUNCTIONS AND DISCOVERING LIPID BIOMARKERS FOR DISEASES. ADDRESSING THE ABSENCE OF RAPID LIPID PROFILING METHODS AND THAT PROVIDE SUFFICIENT STRUCTURAL DETAILS IS CRITICAL FOR PREDICTING, CONTROLLING, AND ENGINEERING LIPID METABOLISM ON A LARGE SCALE FOR BIOMEDICAL AND PHENOTYPIC SCREENING. MY LONG-TERM GOAL IS TO ENABLE THE ELUCIDATION OF THE DETAILED MOLECULAR MECHANISMS OF LIPID METABOLISM THROUGH ADVANCING LIPIDOMIC PROFILING WITH HIGH STRUCTURAL SPECIFICITY AND TO UNRAVEL THE RELATIONSHIP BETWEEN SPECIFIC LIPIDS AND ASSOCIATED FUNCTIONS IN BIOLOGICAL SYSTEMS AND DISEASES. TO ACHIEVE THIS, WE PROPOSE DEVELOPING A NEXT-GENERATION LIPIDOMICS PIPELINE USING MASS SPECTROMETRY-BASED TECHNOLOGIES AND ADVANCED BIOINFORMATICS CAPABILITIES. OUR APPROACH INVOLVES DEVELOPING A MULTI-DIMENSIONAL LIPIDOMIC PLATFORM USING HIGH-RESOLUTION STRUCTURES FOR LOSSLESS ION MANIPULATIONS-BASED ION MOBILITY SPECTROMETRY-MASS SPECTROMETRY, ADVANCED FRAGMENTATION TECHNIQUES, AND GAS-PHASE REACTIONS FOR EFFECTIVE LIPID STRUCTURE ELUCIDATION, INCLUDING RESOLVED ISOMER SEPARATION AND DETERMINING DOUBLE BOND LOCATIONS. THIS INTEGRATIVE PLATFORM WILL BE COUPLED WITH LIQUID CHROMATOGRAPHY AND A NOVEL DATA ACQUISITION APPROACH UTILIZING BOTH DATA-DEPENDENT ACQUISITION AND DATA- INDEPENDENT ACQUISITION FOR A COMPREHENSIVE ANALYSIS OF LIPIDS IN COMPLEX SAMPLES. TO ENSURE ROBUST DATA PROCESSING, LIPID IDENTIFICATION AND STRUCTURE ELUCIDATION, WE WILL DEVELOP ADVANCED BIOINFORMATICS PIPELINES USING ARTIFICIAL INTELLIGENCE APPROACHES. ADDITIONALLY, A HIGH-THROUGHPUT AND QUANTITATIVE WORKFLOW UTILIZING ONLINE SOLID-PHASE EXTRACTION FOR RAPID LIPID SCREENING WILL BE DEVELOPED. THE ROBUSTNESS OF THIS WORKFLOW AND ADVANCED BIOINFORMATICS PIPELINE WILL BE VALIDATED BY FULLY PROFILING THE YEAST LIPIDOME. A COMPREHENSIVE AND STRUCTURALLY DETAILED LIPID ATLAS FOR THE YEAST KNOCKOUT COLLECTION WILL BE CONSTRUCTED AND PROVIDE A FOUNDATION FOR UNDERSTANDING LIPID METABOLISM AND ASSOCIATED FUNCTIONS ANALOGOUS TO HUMAN GENES. WE ANTICIPATE THAT THIS PLATFORM WILL BECOME A FUNDAMENTAL CAPABILITY FOR LIPID PROFILING IN BIOMEDICAL RESEARCH TO UNRAVEL THE INTRICATE RELATIONSHIP BETWEEN LIPIDS AND ASSOCIATED FUNCTIONS IN BIOLOGICAL SYSTEMS AND HUMAN HEALTH. FURTHERMORE, WE EXPECT THIS INNOVATIVE APPROACH TO FACILITATE THE DISCOVERY OF LIPID BIOMARKERS FOR DISEASE DIAGNOSTICS AND DRUG DEVELOPMENT.

INVESTIGATION OF RADIATIVE - DYNAMICAL FEEDBACKS IN CIRRUS \NCIRRUS CLOUD-RADIATION INTERACTIONS ARE AN IMPORTANT ASPECT OF THE EARTH\''S ENERGY BALA

ENGINEERING AND PERFORMANCE OF MAGNETIC PARTICLE IMAGING

INNOVATIVE SENSORS FOR PIPELINE CRAWLERS TO ASSESS ALL PIPELINE DEFECTS AND CONDITIONS

TECHNICAL STUDIES

SINGLE-CELL (PHOSPHO-)PROTEOMICS PLATFORM FOR FUNCTIONAL ANALYSIS OF TUMOR MICROENVIRONMENT - ABSTRACT TUMOR MICROENVIRONMENT (TME) IS A COMPLEX ECOSYSTEM COMPRISED OF CANCER CELLS, IMMUNE CELLS, STROMAL CELLS, AND OTHER CELL TYPES. THEY INTERACT AND COLLECTIVELY DETERMINE DISEASE PROGRESSION AND RESPONSE TO THERAPY. TO ACHIEVE A COMPLETE PICTURE OF TME, MULTI-OMICS SINGLE-CELL TECHNOLOGIES ARE NEEDED TO CHARACTERIZE DIVERSE INDIVIDUAL CELLS WITHIN TME AT BOTH GENOTYPE AND PHENOTYPE LEVELS. SUCH ANALYSIS HOLDS PROMISE TO MOVE TOWARDS PRECISION MEDICINE. HOWEVER, SINGLE-CELL PROTEOMICS TECHNOLOGIES ARE LAGGING FAR BEHIND OTHER SINGLE-CELL OMICS TECHNOLOGIES. MANY STUDIES HAVE SHOWN THAT MRNA ABUNDANCE IS A POOR SURROGATE FOR PROTEIN ABUNDANCE AND CANNOT PROVIDE ANY INSIGHTS INTO PROTEIN ACTIVITY REGULATED BY PROTEIN PHOSPHORYLATION. THEREFORE, SINGLE-CELL (PHOSPHO-)PROTEOMICS IS CRITICALLY IMPORTANT TO PROVIDE COMPLEMENTARY DATA THAT CANNOT BE ACHIEVED BY OTHER OMICS TECHNOLOGIES. ANTIBODY-BASED IMMUNOASSAYS ARE PRIMARILY USED FOR FUNCTIONAL ANALYSIS OF SINGLE CELLS, BUT THEY ONLY CAN OPEN A SMALL WINDOW INTO THE COMPLEX TME ECOSYSTEM DUE TO THEIR INHERENT LIMITATIONS. MASS SPECTROMETRY (MS)-BASED (PHOSPHO-)PROTEOMICS IS A POWERFUL TOOL FOR GENOME-SCALE PROTEOME PROFILING AND SITE-SPECIFIC QUANTIFICATION OF 1,000S OF PHOSPHORYLATION SITES. HOWEVER, IT DOES NOT MEET THE MERIT FOR SINGLE-CELL (PHOSPHO-)PROTEOMICS ANALYSIS. THERE ARE THREE MAJOR CHALLENGES THAT NEED TO BE ADDRESSED: 1) LOW RECOVERY FOR PHOSPHO-ENRICHMENT, 2) INSUFFICIENT MS SENSITIVITY, 3) LOW SAMPLE THROUGHPUT. WE PROPOSE TO DEVELOP A SINGLE-CELL (PHOSPHO-)PROTEOMICS PLATFORM TO ADDRESS THESE THREE CHALLENGES FOR ROBUST RAPID ANALYSIS OF SINGLE CELLS AT BOTH PROTEOME AND PHOSPHOPROTEOME LEVELS. THE PROJECT FEASIBILITY IS STRONGLY SUPPORTED BY OUR RECENT PROGRESS IN MANY ASPECTS OF TECHNOLOGY DEVELOPMENT. THE NEW PLATFORM WILL BE DEVELOPED THROUGH INTEGRATION OF A HIGH-RECOVERY SAMPLE PREPARATION PLATFORM FOR SINGLE-CELL PROCESSING AND PHOSPHO-ENRICHMENT WITH A HIGH-EFFICIENCY MS PLATFORM TO ENHANCE MS DETECTION SENSITIVITY AND SAMPLE MULTIPLEXING TO IMPROVE SAMPLE THROUGHPUT. WE ENVISION THAT THE SINGLE-CELL MS PLATFORM WILL EVENTUALLY BECOME AN INDISPENSABLE TOOL FOR ROBUST, RAPID, DEEP (PHOSPHO-)PROTEOMIC ANALYSIS OF SINGLE CELLS AND TME. IN TURN, IT WILL MAKE SUBSTANTIAL CONTRIBUTIONS TO IMPROVE OUR UNDERSTANDING OF CANCER BIOLOGY AND ACCELERATE THE MOVEMENT TOWARDS PRECISION MEDICINE.

SPATIAL ANALYSIS OF ALCOHOLIC HEPATITIS LIVER TISSUE

MASS SPECTROMETRY IMAGING: LINKING NEURODEGENERATION WITH ENVIRONMENTAL EXPOSURE

THE PURPOSE OF THIS PROJECT IS TO BUILD A BROAD INTERNATIONAL COMMUNITY TO DRIVE SOLUTIONS TO STOP MOSQUITOS THAT CARRY ZIKA AND OTHER DISEASES.

NANOLITER-SCALE AFFINITY PURIFICATION MASS SPECTROMETRY FOR SMALL NUMBERS OF HAIR CELLS - PROJECT SUMMARY/ABSTRACT HAIR CELLS ARE THE SENSORY CELLS OF THE INNER EAR THAT CARRY OUT THE ESSENTIAL FUNCTION OF MECHANOTRANSDUCTION EVOKED BY SOUND AND HEAD MOVEMENT. IT IS FUNDAMENTALLY IMPORTANT TO CHARACTERIZE GLOBAL PROTEIN EXPRESSIONS AND THEIR INTERACTIONS IN HAIR CELLS IN ORDER TO UNDERSTAND THE MOLECULAR MECHANISM. HOWEVER, ONE OF THE GREATEST CHALLENGES IN PROTEIN CHARACTERIZATION IS THE LOW NUMBER OF HAIR CELLS PRESENTED IN EACH INNER-EAR ORGAN, WHICH URGES US TO DEVELOP SENSITIVE ANALYTICAL APPROACHES. TO THIS END, OUR LABS DEVELOP A MICROFLUIDIC SAMPLE PREPARATION PLATFORM, TERMED AS NANOPOTS (NANODROPLET PROCESSING IN ONE POT FOR TRACE SAMPLES), FOR PROTEOMICS ANALYSIS OF LOW-INPUT BIOMATERIALS BY DOWNSCALING PROCESSING VOLUMES TO <200 NL. WHILE NANOPOTS IS WELL DEMONSTRATED TO IDENTIFY AND QUANTIFY PROTEIN EXPRESSION FROM SINGLE HAIR CELLS, IT INFORMS NOTHING ON HOW PROTEINS INTERACT WITH EACH OTHER TO IMPLEMENT THEIR FUNCTIONS. THE OVERALL OBJECTIVE OF THIS PROJECT TO DEVELOP A SENSITIVE NANOLITER DROPLET-BASED AFFINITY PURIFICATION WITH MASS SPECTROMETRY (NANOAP-MS) PLATFORM TO IDENTIFY PROTEIN INTERACTING PARTNERS USING FEWER THAN 1000 HAIR CELLS ISOLATED FROM UTRICLES OR COCHLEAS OF THE MOUSE EAR. THE CENTRAL HYPOTHESIS IS THAT THE OVERALL SENSITIVITY OF AP-MS ASSAY CAN BE SIGNIFICANTLY IMPROVED BY PERFORMING AFFINITY PURIFICATION IN NANOLITER DROPLETS. THEORY SUGGESTS THIS HYPOTHESIS SHOULD BE CORRECT BECAUSE: 1) IMPROVED PROTEIN CONCENTRATIONS BY LYSING CELLS IN NANOLITER VOLUMES WILL IMPROVE PROTEIN-BEAD BINDING EFFICIENCY; 2) REDUCING THE AMOUNTS OF AFFINITY BEADS WILL REDUCE NON-SPECIFIC BINDING, WHICH CAN OTHERWISE DWARF SPECIFIC BINDING; AND 3) IMPROVED LC-MS WILL PROVIDE SUFFICIENT ANALYTICAL SENSITIVITY TO MEASURE LOW ABUNDANCE PROTEINS. THE CENTRAL HYPOTHESIS WILL BE TESTED BY PURSUING TWO SPECIFIC AIMS: 1) TO ESTABLISH A NANOLITER DROPLET-BASED AP-MS WORKFLOW; AND 2) TO APPLY THIS WORKFLOW FOR IDENTIFICATION OF MYO7A AND GIPC3 BINDING PARTNERS IN MOUSE HAIR CELLS. WE EXPECTED THE PROPOSED NANOAP-MS PLATFORM WILL INCREASE SENSITIVITY BY A FACTOR OF 103 OR MORE AND ALLOW US TO CHARACTERIZE LOW-ABUNDANCE PROTEIN INTERACTION PARTNERS. THIS RESEARCH IS HIGHLY INNOVATIVE BECAUSE THE NANOAP-MS PLATFORM WILL BE THE FIRST OF ITS KIND TO RELIABLY MEASURE PROTEIN-PROTEIN INTERACTIONS USING A SMALL NUMBER OF PRIMARY CELLS ISOLATED FROM PHYSIOLOGICAL ENVIRONMENT, INCLUDING ANIMAL MODELS OR HUMAN BIOPSIES. STATEMENT OF IMPACT: AS AP-MS HAS EMERGED AS POWERFUL TECHNOLOGY TO DISCOVER PROTEIN INTERACTION PARTNERS AND ESTABLISH PROTEIN-PROTEIN-INTERACTION NETWORKS, THE NANOAP-MS TECHNOLOGY WILL ENABLE TO EXAMINE IMPORTANT PROTEIN-PROTEIN INTERACTIONS IN SMALL NUMBERS OF CELLS ISOLATED BY MICROPIPETTE, FACS, OR LASER-CAPTURE MICRODISSECTION, OR TO EXAMINE EXCEPTIONALLY LOW- ABUNDANCE INTERACTIONS LIKE THOSE PRESENT IN THE HAIR CELL'S MECHANOTRANSDUCTION COMPLEX.

DEFINING THE FUNCTIONAL DYNAMICS OF THE MICROBIOME

COLLABORATIVE RESEARCH: BIOLOGY-GUIDED NEURAL NETWORKS FOR DISCOVERING PHENOTYPIC TRAITS

BIOMATERIALS AS DECORPORATION AGENTS FOR RADIONUCLIDES

EVALUATING PLASMA AND URINE PORPHYRINS AS BIOMARKERS OF ASD

THIS PROPOSAL LEVERAGES FINDINGS FROM A 2016 JOINT BATTELLE AND NASA ENERGY MANAGEMENT STAKEHOLDER IDEATION WORKSHOP AS WELL AS A RELATIONSHIP WITH THE DEPARTMENT OF ENERGY S PARTNERSHIP FOR ENERGY SECTOR CLIMATE RESILIENCE TO STRENGTHEN CONNECTIONS BETWEEN THE EARTH SCIENCE COMMUNITY AND ELECTRIC UTILITY DATA END USERS AS WELL AS BUILD CAPACITY FOR DOMESTIC ELECTRIC UTILITY STAKEHOLDERS TO ACCESS AND APPLY EARTH OBSERVATION (EO) INFORMATION IN RESILIENCE AND RENEWABLE ENERGY PROGRAM PLANNING. THE TRANSDISCIPLINARY BATTELLE TEAM IS ESPECIALLY QUALIFIED TO MANAGE AND IMPLEMENT THIS WORK IN A COST EFFECTIVE AND TECHNICALLY INNOVATIVE WAY. ENERGY SYSTEMS ARE CRITICAL INFRASTRUCTURE WITH ELECTRICITY SERVING SOCIETY FROM COOKING AND LIGHTING TO COMMUNICATIONS AND TRANSPORTATION. HOWEVER IMPACTS FROM CLIMATE VARIABILITY AND CHANGE SUCH AS EXTREME WEATHER OR SEA LEVEL RISE THREATEN ENERGY RELIABILITY AND COMMUNITY RESILIENCE. HOWEVER VULNERABILITIES AND NEEDS IN THE ENERGY SECTOR VARY WIDELY BY COMPONENT REGION AND GEOGRAPHY. A SUCCESSFUL STRATEGY FOR ADDRESSING RESILIENCE PLANNING AND UPTAKE OF RENEWABLE ENERGY MUST INCLUDE ENGAGEMENT WITH UTILITY PROVIDERS WHO CAN BUILD SUCH ACTIONS INTO ROUTINE PLANNING AND MAINTENANCE ACTIVITIES. FINDINGS FROM THE 2016 ENERGY MANAGEMENT WORKSHOP SUGGEST THAT THE CONNECTIONS BETWEEN EARTH SCIENCE RESEARCHERS AND UTILITY END USERS MUST BE STRENGTHENED FOR NEW PRODUCTS TOOLS AND DATA PACKAGES TO MEET UTILITY USER NEEDS. THE BATTELLE TEAM WILL ENGAGE THE EARTH SCIENCE COMMUNITY UTILITY END USERS AND OTHER GOVERNMENT OR RESEARCH STAKEHOLDERS IN STRENGTHENING THE ABILITY OF UTILITY END USERS TO ACCESS AND USE EO DATA. THE PROPOSED APPROACH UTILIZES A CAPACITY BUILDING FRAMEWORK TO CONDUCT A THOROUGH NEEDS ASSESSMENT UTILIZING THE UTILITY PARTNERSHIP AS A KEY ENTRY POINT TO ENGAGING WITH THE END USER COMMUNITY. AN ADVISORY GROUP OF TECHNICAL EXPERTS AND FEDERAL AGENCY REPRESENTATIVES WILL ALSO BE FORMED TO MAXIMIZE STAKEHOLDER ENGAGEMENT. THE NEEDS ASSESSMENT WILL SEEK TO QUANTIFY TECHNICAL CAPACITY AND GAPS CURRENT EO DATA USAGE AND ASPIRATIONAL GOALS ON POSSIBLE NEAR-TERM APPLICATION AREAS FOR EO UPTAKE. BASED ON THE NEEDS ASSESSMENT FINDINGS A SERIES OF TECHNICAL ASSISTANCE AND CAPACITY BUILDING ACTIVITIES WILL BE DEVELOPED. PRELIMINARY TRAINING TOPICS MAY INCLUDE SATELLITE DATA TYPES AND CURRENT APPLICATIONS FOR UTILITY APPLICATIONS; DATA PROCESSING FORMATTING AND VISUALIZATION FOR UTILITY APPLICATIONS; OR INCORPORATING EO DATA AND TOOLS INTO RESILIENCE PLANNING OR RENEWABLE ENERGY UPTAKE (ASSESSMENT MONITORING ETC.) FOR UTILITY APPLICATIONS. CASE STUDIES ON CURRENT AND ASPIRATIONAL EO APPLICATIONS OR EXISTING TOOLS AND PRODUCTS WILL BE DEVELOPED USING INFOGRAPHICS AND/ OR ESRI STORY MAPS AND DISTRIBUTED THROUGH TARGETED LISTSERVS AND SOCIAL MEDIA. A PRELIMINARY CASE STUDY TOPIC MAY INCLUDE USING NORMALIZED DIFFERENCE VEGETATION INDEX (NDVI) FROM VIIRS AND MODIS PRECIPITATION DATA FROM GPM AND SOIL MOISTURE DATA FROM SMAP DATA TO UNDERSTAND FLOOD RISK. THE BATTELLE TEAM WILL ALSO ENGAGE WITH THE EARTH SCIENCE COMMUNITY VIA PARTICIPATION IN TECHNICAL CONFERENCES AND THROUGH THE DISTRIBUTION OF UTILITY DATA NEEDS VIA PUBLICATION IN KEY SCIENTIFIC AND POPULAR JOURNALS. GREATER INFORMATION SHARING NETWORKS ARE AN IMPORTANT STEP IN PROVIDING AND STRENGTHENING LINKAGES BETWEEN DATA PROVIDERS AND DATA USERS. THE PROPOSED WORK MEETS THE GROUP ON EARTH OBSERVATIONS (GEO) STATED NEED TO IMPROVE THE AVAILABILITY ACCESS AND USE OF EOS TO INFORM DECISIONS AND BENEFIT SOCIETY. THE ATTENTION PAID TO SUSTAINED STAKEHOLDER ENGAGEMENT ONGOING EVALUATION AND INFORMATION SHARING WITH BOTH SCIENTIFIC AND END-USER COMMUNITIES ALSO SUPPORTS GEO VISION FOR ENERGY (GEOVENER) BY CONTRIBUTING TO A PROCESS THAT IS BETTER-INFORMED TO SUPPORT END-TO-END PRODUCTION SYSTEMS AND RESULTS IN ACTIONABLE MEASURES TO ADDRESS CRITICAL GLOBAL AND REGIONAL CHALLENGES AND OPPORTUNITIES IN ENERGY SERVICES.

INTERGOVERNMENTAL MOBILITY ASSIGNMENT

INFORMING CANCER EPIDEMIOLOGY THROUGH THE IDENTIFICATION OF DIFFERENTIATING CHEMICAL CONSTITUENTS OF CIGARILLO SMOKE - PROJECT SUMMARY CIGAR SMOKING IS ASSOCIATED WITH MULTIPLE NEGATIVE HEALTH OUTCOMES, INCLUDING INCREASED RISKS FOR VARIOUS TYPES OF CANCER. CIGAR USE IN THE U.S. INCREASED BETWEEN 2000 AND 2011 EVEN AS CIGARETTE SALES DECLINED OVER THE SAME TIME PERIOD. CIGAR USE IS COMMON AMONG MINORITY YOUTH AND AS A VEHICLE TO ADMINISTER CANNABIS. WITHIN THE PRODUCT CLASS OF CIGARS, CIGARILLOS ARE THE MOST COMMONLY USED IN THE U.S. AND ARE ASSOCIATED WITH SPECIFIC PUBLIC HEALTH CONCERNS, INCLUDING HIGHER RATES OF USE BY YOUNG ADULTS (AGES 18–24) IN CONTRAST TO OLDER ADULTS AND DIFFERENT PATTERNS OF CO-USE OF MULTIPLE TOBACCO PRODUCTS. THUS, IT IS IMPORTANT TO IMPROVE THE UNDERSTANDING OF PARTICULAR FACTORS RELATED TO CIGARILLO USE IN ORDER TO INFORM CANCER EPIDEMIOLOGY. IN THE PROPOSED RESEARCH, WE WILL IDENTIFY THE CHEMICAL CONSTITUENTS OF MAINSTREAM CIGARILLO SMOKE THAT ARE DIFFERENT THAN THOSE OF MAINSTREAM CIGARETTE SMOKE THROUGH NON-TARGETED CHEMICAL ANALYSIS (I.E., THE IDENTIFICATION OF CHEMICALS THAT ARE NOT SPECIFIED PRIOR TO ANALYZING A GIVEN SAMPLE). THE EXPECTED RESULTS ARE IMPORTANT FOR EPIDEMIOLOGICAL PURPOSES IN THAT THEY CAN REVEAL CARCINOGENS IN CIGARILLO SMOKE BEYOND THOSE KNOWN TO BE COMMONLY ASSOCIATED WITH TOBACCO SMOKE IN GENERAL, THUS PROVIDING A BETTER UNDERSTANDING OF ENVIRONMENTAL RISK FACTORS IN EPIDEMIOLOGICAL RESEARCH. FURTHERMORE, THE IDENTIFIED COMPOUNDS CAN BE USED IN LATER RESEARCH PROJECTS TO INFORM THE DEVELOPMENT OF BIOMARKERS OF EXPOSURE THAT CAN BE USED IN INDIVIDUAL OR POPULATION BASE SAMPLING TO ESTIMATE CIGARILLO EXPOSURE. TO ACHIEVE OUR RESEARCH OBJECTIVE, WE WILL EMPLOY TWO-DIMENSIONAL GAS CHROMATOGRAPHY–TIME-OF-FLIGHT MASS SPECTROMETRY (GC×GC-TOFMS), AN ADVANCED ANALYTICAL CHEMISTRY TECHNIQUE WITH POWERFUL CAPABILITIES FOR NON-TARGETED CHEMICAL ANALYSIS. GC×GC-TOFMS WILL BE USED TO COLLECT NON-TARGETED ANALYTICAL CHEMISTRY DATA FOR BOTH CIGARILLO SMOKE AND CIGARETTE SMOKE. THE DATA FROM THE TWO PRODUCT (SUB)CLASSES WILL BE COMPARED AGAINST ONE ANOTHER, AND THOSE SIGNALS THAT DIFFERENTIATE THE PRODUCT (SUB)CLASSES WILL BE ASSESSED USING COMPUTATIONAL TOXICOLOGY DATABASES (E.G., THE ENVIRONMENTAL PROTECTION AGENCY COMPTOX CHEMICALS DASHBOARD) TO DETERMINE WHICH ARE MOST LIKELY FROM COMPOUNDS THAT WOULD PRESENT SIGNIFICANT CARCINOGENICITY CONCERNS IN CIGARILLO SMOKE. ADDITIONAL ANALYSES WILL THEN BE PERFORMED USING AUTHENTIC CHEMICAL STANDARDS TO CONFIRM THE CHEMICAL IDENTITIES AND TO QUANTIFY THE AMOUNTS IN BOTH CIGARILLO SMOKE AND CIGARETTE SMOKE. THE PROPOSED INNOVATIVE RESEARCH IS DESIGNED TO IDENTIFY AND QUANTIFY SPECIFIC CHEMICAL CONSTITUENTS (1) THAT DIFFERENTIATE CIGARILLO SMOKE FROM CIGARETTE SMOKE, AND (2) THAT ARE POTENTIALLY CARCINOGENIC. THE RESULTS WILL COMPLEMENT EPIDEMIOLOGICAL DATA REGARDING THE IMPACT TO PUBLIC HEALTH ASSOCIATED WITH CIGARILLO USE. THIS INVESTIGATION WILL THUS ADVANCE CANCER RESEARCH THROUGH EXPANDING KNOWLEDGE ABOUT CANCER RISKS FOR THOSE POPULATIONS MOST AFFECTED BY CIGARILLO SMOKING.

EFFECT OF TRUE PUFF PROFILE REPLICATION ON MACHINE-GENERATED SMOKE CONSTITUENTS

DEVELOPMENT OF SELECTIVE NANOPOROUS SORBENTS FOR RADIONUCLIDE DECORPORATION

HIGH-THROUGHPUT MULTIDIMENSIONAL BIOSEPARATIONS FOR NEXT-GENERATION PROTEOMICS

MULTIDIMENSIONAL PROTEOMICS PLATFORM

COMBINED EXTRACTION METHOD FOR MITOCHONDRIAL DNA AND PROTEINS FROM HAIR FOR HUMAN IDENTIFICATION