University Of Washington

INTERNATIONAL AIDS EDUCATION AND TRAINING CENTER

WASHINGTON NATIONAL PRIMATE RESEARCH CENTER

SUPPORTING THE PROVISION OF COMPREHENSIVE HIV TESTING, TREATMENT, CARE, AND SUPPORT SERVICES IN THE REPUBLIC OF ZIMBABWE UNDER THE PRESIDENT'S EMERGENCY PLAN FOR AIDS RELIEF

FUNDING TO COVER COSTS ASSOCIATED WITH SIGNIFICANT CHANGES TO THE DELIVERY OF INSTRUCTION DUE TO THE ONGOING COVID-19 PANDEMIC.

COOPERATIVE INSTITUTE FOR CLIMATE, OCEAN, AND ECOSYSTEM STUDIES (CICOES)

JOINT INSTITUTE FOR THE STUDY OF THE ATMOSPHERE AND OCEAN

EMS NETWORK DATA COORDINATING CENTER

INSTITUTE OF TRANSLATIONAL HEALTH SCIENCES

EMERGENCY AID TO STUDENTS DUE TO COVID-19 PANDEMIC CRISIS.

INTERNATIONAL AIDS EDUCATION AND TRAINING CENTER

UNIVERSITY OF WASHINGTON CENTER FOR AIDS RESEARCH

EXPERIMENTAL NUCLEAR PHYSICS

JOINT INSTITUTE FOR THE STUDY OF THE ATMOSPHERE AND OCEAN (JISAO).

JOINT INSTITUTE FOR THE STUDY OF THE ATMOSPHERE AND OCEAN

THE WWAMI RCE FOR BIODEFENSE AND EMERGING ID

NATIONAL PRIMATE RESEARCH CENTER

R/V THOMAS G. THOMPSON SHIP OPERATIONS 2018-2022

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

INSTITUTE OF TRANSLATIONAL HEALTH SCIENCES

INSTITUTE FOR NUCLEAR THEORY

NATIONAL ALZHEIMERS COORDINATING CENTER (NACC)

NATIONAL CENTER FOR QUALITY TEACHING AND LEARNING

NATIONAL ALZHEIMER'S COORDINATING CENTER - PROJECT SUMMARY/ABSTRACT NACC (AS U01 AG016976, AT UNIVERSITY OF WASHINGTON) HAS BEEN ACTIVE SINCE 1999. THE EXISTING NACC INFRASTRUCTURE IS DESCRIBED IN THE FACILITIES AND RESOURCES SECTION OF THIS APPLICATION. THE BROAD GOALS OF THE PAST FUNDING CYCLES ARE CONSISTENT WITH THOSE OF THE CURRENT U24 RFA — THAT IS, TO SERVE AS: A.) THE CENTRAL HUB FOR ORGANIZING AND ENABLING COMMUNICATION WITHIN AND OUTSIDE OF THE ADRC PROGRAM, INCLUDING ANNUAL MEETINGS AND STEERING COMMITTEES; B.) A NATIONAL DATA RESOURCE, COLLECTING DATA FROM THE ALZHEIMER'S DISEASE RESEARCH CENTERS (ADRCS) AS WELL AS AFFILIATED DATA AND SAMPLE REPOSITORIES; AND C.) A FACILITATOR OF CURRENT AND FUTURE AD/ADRD RESEARCH. NACC HAS CONSIDERABLE EXPERIENCE AND SUCCESS IN REACHING THESE GOALS, AND IS POSITIONED FOR CONTINUED SUCCESS IN A RAPIDLY ADVANCING FIELD. NEW DATA AND METHODS ARE APPEARING IN AREAS SUCH AS BIOMARKERS, NEUROPATHOLOGY, AND TESTS FOR EARLY DETECTION. THROUGH THE STRATEGIC ADOPTION OF TECHNOLOGICAL ADVANCES, WE WILL BUILD ON THESE ACCOMPLISHMENTS AT AN ACCELERATED PACE. BUILDING ON OUR ALREADY SIGNIFICANT CAPABILITIES, WE WILL: PROMOTE AND BROADEN COMMUNICATION WITHIN AND OUTSIDE OF THE ADRC PROGRAM; EXPAND INFORMATICS CAPABILITIES OF NACC CONSISTENT WITH FAIR PRINCIPLES; CONDUCT AND SUPPORT METHODOLOGIC AND APPLIED RESEARCH, LEVERAGING DEEP EXPERTISE IN BIOSTATISTICS AND DATA SCIENCE; AND SUPPORT EARLY-CAREER RESEARCH SCIENTISTS BY PROVIDING PEER-REVIEWED COMPETITIVE FUNDING FOR SEVERAL “JUNIOR INVESTIGATORS” EACH YEAR. WE AIM TO CONTINUE TO IMPROVE OUR APPROACH IN EACH ARENA BY COMBINING TIME-TESTED APPROACHES WITH THE NEW TOOLS AND INNOVATIONS WE ARE DEVELOPING TO MEET THE CHANGING SCIENTIFIC, TECHNOLOGICAL, AND COMMUNICATION NEEDS OF THE NIA ADRC PROGRAM AND THE FIELD.

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

NAMIBIA MECHANISM FOR PUBLIC HEALTH ASSISTANCE, CAPACITY, AND TECHNICAL SUPPORT II (NAM-PHACTS II) UNDER THE PRESIDENT'S EMERGENCY PLAN FOR AIDS RELIEF (PEPFAR)

ZAZIC CONSORTIUM: SUPPORTING FULL HIV/AIDS EPIDEMIC CONTROL IN ZIMBABWE THROUGH EXPANDED VOLUNTARY MEDICAL MALE CIRCUMCISION (VMMC)

INSTITUTE FOR TRANSLATIONAL HEALTH SCIENCE (UL1)

MACHINE LEARNING-ENABLED DESIGN OF PROTOTYPE PATHOGEN VACCINES AND ANTIBODIES - PROJECT SUMMARY – OVERALL: MACHINE LEARNING-ENABLED DESIGN OF PROTOTYPE PATHOGEN VACCINES AND ANTIBODIES WE PROPOSE A HIGHLY SYNERGISTIC CENTER FOCUSED ON DEVELOPING END-TO-END STRATEGIES FOR PANDEMIC PREPAREDNESS VACCINE DEVELOPMENT FOR BUNYAVIRUSES AND PARAMYXOVIRUSES. OUR CENTER BRINGS TOGETHER FIVE RESEARCH INSTITUTIONS WITH COMPLEMENTARY AND SYNERGISTIC EXPERTISE IN COMPUTATIONAL PROTEIN DESIGN, STRUCTURE-BASED VACCINE DESIGN, MRNA VACCINES, STRUCTURAL BIOLOGY, VIRAL ENTRY, VIRAL DIVERSITY AND EVOLUTION, ANIMAL MODEL DEVELOPMENT, HIGH BIOSAFETY-LEVEL CONTAINMENT VIROLOGY, VACCINOLOGY, AND VACCINE PROCESS DEVELOPMENT AND TECHNOLOGY TRANSFER. OUR TEAM HAS REAL-WORLD EXPERIENCE IN VACCINE AND BIOLOGICS PRODUCT DEVELOPMENT IN BOTH ACADEMIC AND INDUSTRY SETTINGS. OUR CENTER COMPRISES FIVE SCIENTIFIC PROJECTS SUPPORTED BY THREE SCIENTIFIC CORES, AN ADMINISTRATIVE CORE, AND A DATA MANAGEMENT CORE. OUR SCIENTIFIC PROJECTS INCLUDE: 1) DEVELOPMENT OF COMPUTATIONAL METHODS FOR VACCINE AND BIOLOGICS DESIGN, 2) FUNDAMENTAL RESEARCH ON VIRAL ENTRY AND RECEPTORS, 3) ANTIGEN DESIGN, 4) PROTEIN NANOPARTICLE VACCINE DEVELOPMENT, AND 5) MRNA VACCINE DEVELOPMENT. WE WILL STRUCTURE OUR EFFORTS IN TWO PHASES: IN PHASE 1 (YEARS 1-3) WE WILL FOCUS ON DEVELOPING VACCINES FOR OUR PROTOTYPE PATHOGENS AND IN PHASE 2 (YEARS 4-5) WE WILL APPLY THOSE LEARNINGS TO TWO NEW BUNYAVIRUSES AND TWO NEW PARAMYXOVIRUSES TO DEMONSTRATE THAT OUR COMPUTATIONAL AND EXPERIMENTAL APPROACHES GENERALIZE ACROSS VIRAL FAMILIES. OUR PROTOTYPE PATHOGENS ARE: LASSA VIRUS (LASV; ARENAVIRUSES), RIFT VALLEY FEVER VIRUS (RVFV; PHENUIVIRUSES), AND HENDRA VIRUS (HEV; PARAMYXOVIRUSES). WE CAREFULLY SELECTED OUR PROTOTYPES AS WE BELIEVE THEY PRESENT SPECIFIC VACCINE DESIGN CHALLENGES WHICH, IF WE ARE SUCCESSFUL IN SOLVING, WILL FACILITATE THE DEVELOPMENT OF VACCINES AGAINST RELATED VIRUSES. SIMULTANEOUSLY, THE ANTIGENS FROM VIRUSES IN THESE THREE FAMILIES HAVE SOME SIMILARITIES THAT WILL GIVE RISE TO SYNERGIES IN OUR DESIGN APPROACHES. THE STRUCTURE OF OUR CENTER WILL ALLOW MAXIMAL SYNERGY BETWEEN OUR GROUPS IN PURSUIT OF ITS CENTRAL OUTPUT: TO DEFINE GENERALIZABLE APPROACHES AND TOOLS TO DEVELOP VACCINES AND BIOLOGICS FOR EMERGING PATHOGENS WITH PANDEMIC POTENTIAL.

PRENATAL?AND EARLY CHILDHOOD PATHWAYS?TO?HEALTH: ?AN INTEGRATED MODEL OF CHEMICAL AND SOCIAL EXPOSURES, BIOLOGICAL MECHANISMS, AND SEX-SPECIFIC EFFECTS ON NEURODEVELOPMENT AND RESPIRATORY OUTCOMES

ALZHEIMER'S DISEASE RESEARCH CENTER

NSF ENGINEERING RESEARCH CENTER FOR SENSORIMOTOR NEURAL ENGINEERING

GH15-1615, NAMIBIA: PROGRAM AREA B - SUPPORT FOR CLINICAL SERVICE DELIVERY IN NAMIBIA

MACHINE LEARNING-ENABLED DESIGN OF NOROVIRUS AND HERPESVIRUS VACCINES -   WE PROPOSE A HIGHLY INTEGRATED AND SYNERGISTIC PROGRAM TO DEVELOP UNIVERSAL VACCINE DESIGN APPROACHES THAT CAN BE BROADLY APPLIED TO VIRAL AND BACTERIAL PATHOGENS. WE WILL DEMONSTRATE THE VALIDITY OF OUR APPROACHES BY DEVELOPING VACCINES FOR THREE HUMAN HERPESVIRUSES THAT HAVE REMAINED OUT OF REACH DESPITE EFFORTS BY MANY VACCINE DEVELOPERS: HSV-1, HSV-2, AND EBV. HERPESVIRUSES ARE RESPONSIBLE FOR SUBSTANTIAL MORBIDITY AND MORTALITY WORLDWIDE, AND SEVERAL OF THEM ARE STRONGLY LINKED TO CHRONIC ILLNESSES INCLUDING CANCER AND NEURODEGENERATIVE DISEASES. DESPITE THEIR SIGNIFICANT PUBLIC HEALTH BURDEN, THERE ARE NO LICENSED VACCINES FOR HERPESVIRUSES OTHER THAN FOR VARICELLA-ZOSTER VIRUS, WHICH USE APPROACHES THAT CANNOT BE GENERALIZED TO OTHER FAMILY MEMBERS. THE FAILURE OF EARLIER VACCINE DEVELOPMENT EFFORTS IS DUE TO A LACK OF STABILIZED ANTIGENS AND COMPATIBLE DISPLAY PLATFORMS, AN INCOMPLETE UNDERSTANDING OF THE MECHANISMS OF PROTECTION, AND POOR INDUCTION OF MUCOSAL IMMUNITY, WHICH MAY BE REQUIRED FOR PROTECTION. A DISTINGUISHING FEATURE OF OUR PROGRAM IS THE DEVELOPMENT AND APPLICATION OF INNOVATIVE ARTIFICIAL INTELLIGENCE (AI)-BASED COMPUTATIONAL METHODS FOR ANTIGEN AND PROTEIN NANOPARTICLE VACCINE DESIGN. THE BAKER, DIMAIO, KING, LEE, AND VEESLER LABS AT THE UNIVERSITY OF WASHINGTON WILL INTEGRATE THESE COMPUTATIONAL AND STRUCTURAL METHODS INTO GENERAL WORKFLOWS FOR UNIVERSAL VACCINE DESIGN AND EVALUATION THAT CAN BE APPLIED TO MANY FAMILIES OF VIRAL AND BACTERIAL PATHOGENS. WE WILL COMBINE THIS ABILITY WITH DEEP DISEASE-SPECIFIC EXPERTISE AND HIGH-THROUGHPUT PIPELINES FOR VACCINE PRODUCTION AND EVALUATION, HARNESSING RECENT INNOVATIONS IN MRNA VACCINE MANUFACTURING TO ITERATE BETWEEN THE COMPUTER AND THE LAB TO IMPROVE VACCINE PERFORMANCE. THE BLOOM LAB AT THE FRED HUTCHINSON CANCER CENTER (FRED HUTCH) WILL USE ANALYSES OF HERPESVIRUS EVOLUTION AND HIGH-THROUGHPUT DEEP MUTATIONAL SCANNING TO INFORM VACCINE DESIGN AND EVALUATION. THE GEORGIOU AND LAVINDER GROUP AT THE UNIVERSITY OF TEXAS AT AUSTIN ARE EXPERTS IN B CELL IMMUNOLOGY AND ANTIBODY REPERTOIRE ANALYSES AND WILL COMPREHENSIVELY CHARACTERIZE HUMORAL RESPONSES TO HERPESVIRUS INFECTION AND VACCINATION. THE LEIB LAB AT DARTMOUTH AND THE LUND AND MCGUIRE LABS AT THE FRED HUTCH ARE EXPERTS IN EVALUATING NOVEL HERPESVIRUS VACCINE CANDIDATES AND WILL USE KEY ANIMAL MODELS ESTABLISHED IN THEIR LABORATORIES TO DEVELOP WORKFLOWS THAT ENABLE THE RAPID AND COMPREHENSIVE EVALUATION OF IMMUNE RESPONSES ELICITED BY OUR PROGRAM’S NOVEL AI-DESIGNED VACCINES.  OUR PROGRAM WILL DEFINE THE DETERMINANTS OF PROTECTIVE IMMUNITY AGAINST HERPESVIRUS INFECTION, IDENTIFY UNIVERSAL VACCINE DESIGN APPROACHES AND COMPUTATIONAL DESIGN METHODOLOGIES THAT CAN BE APPLIED ACROSS DIVERSE VIRAL FAMILIES, AND CLINICALLY DE-RISK VACCINE CANDIDATES FOR THREE HERPESVIRUSES WITH MAJOR GLOBAL HEALTH BURDENS. WE EMPHASIZE THAT THE INTEGRATED AI-BASED VACCINE DESIGN APPROACHES AND EXPERIMENTAL WORKFLOWS DEVELOPED AS PART OF THIS PROGRAM WILL BROADLY GENERALIZE TO OTHER VACCINE DESIGN CHALLENGES IN THE FUTURE.

WANPRC MACACA NEMESTRINA SPF BREEDING COLONY

EXPERIMENTAL NUCLEAR PHYSICS

RURAL INITIATIVE IN STEM EDUCATION AND UNDERGRADUATE PREPARATION (RISE UP) GEAR UP PARTNERSHIP

TRANSFORMING CLINICAL PRACTICES INITIATIVE - PTN

DIABETES ENDOCRINOLOGY RESEARCH CENTER

CENTER FOR ECOGENETICS AND ENVIRONMENTAL HEALTH

THE DOG AGING PROJECT: GENETIC AND ENVIRONMENTAL DETERMINANTS OF HEALTHY AGING IN COMPANION DOGS

UNIVERSITY OF WASHINGTON EDUCATION AND RESEARCH CENTER

EFFECTS-RELATED BIOMARKERS OF TOXIC EXPOSURES

HIV SURVEILLANCE FOR EPIDEMIC CONTROL IN MALAWI UNDER THE PRESIDENTS EMERGENCY PLAN FOR AIDS RELIEF

R/V THOMAS G. THOMPSON SHIP OPERATIONS 2012-2017

GAINING EARLY AWARENESS AND READINESS FOR UNDERGRADUATE PROGRAMS (GEAR UP PARTNERSHIP)

GH13-1329, ZIMBABWE: TECHNICAL ASSISTANCE IN SUPPORT OF CLINICAL TRAINING AND MENTORING FOR HIV TREATM

PACIFIC NORTHWEST AGRICULTURAL SAFETY AND HEALTH CENTER-RENEWAL

STRATEGIES FOR IMPROVED SHOCK WAVE LITHOTRIPSY

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

STC: CENTER FOR INTEGRATION OF MODERN OPTOELECTRONIC MATERIALS ON DEMAND

BIOLOGICAL HETEROGENEITY IN ADRD

UW SHIP OPERATIONS, MAINTENANCE, REPAIR AND UPGRADES 2016-2020

UNIVERSITY OF WASHINGTON VACCINE AND TREATMENT EVALUATION UNIT

R/V THOMAS G. THOMPSON SHIP OPERATIONS 2005-2009

PATHOBIOLOGY OF MACROVASCULAR DISEASE IN DIABETES

UNIVERSITY OF WASHINGTON GEAR UP ACHIEVERS PARTNERSHIP

GH14-1403, S. AFRICA: STRENGTHENING THE EVIDENCE BASE AND CAPACITY FOR IMPLEMENTING HIV PREVENTION

IMMUNE MECHANISMS OF FLAVIVIRUS CONTROL

CLINICAL EPIDEMIOLOGY AND PATHOGENESIS OF ASYMPTOMATIC HSV

CENTER: SECURE - COLLABORATIVE RESEARCH SECURITY & INTEGRITY NATIONAL ENVIRONMENT -WITH THIS AWARD SUPPORTED BY THE OFFICE OF THE CHIEF OF RESEARCH SECURITY, STRATEGY & POLICY (OCRSSP), THE U.S. NATIONAL SCIENCE FOUNDATION ESTABLISHES THE SECURE (SAFEGUARDING THE ENTIRE COMMUNITY OF THE U.S. RESEARCH ECOSYSTEM) CENTER TO HELP THE RESEARCH COMMUNITY MITIGATE FOREIGN THREATS TO THE SECURITY AND INTEGRITY OF THE U.S. RESEARCH ENTERPRISE. INTERNATIONAL COLLABORATION IS A VITAL PART OF THE CULTURE AND SUCCESS OF THE US RESEARCH ENTERPRISE AND IS HIGHLY VALUED BY RESEARCHERS. TO SUPPORT THESE RESEARCHERS AND THEIR HOME INSTITUTIONS, AND TO FOSTER A BALANCED APPROACH TO MITIGATING RISK, THE UNIVERSITY OF WASHINGTON (UW) WILL HOST THE NATIONAL SECURE CENTER. THE NATIONAL CENTER WILL SUPPORT AND BE SUPPORTED BY EXPERTS FROM A DOZEN PARTNER ORGANIZATIONS IN FIVE REGIONAL CENTERS ACROSS THE COUNTRY. REGIONAL CENTERS ARE BETTER KNOWN BY RESEARCHERS IN THEIR REGION, WHICH INCREASES PARTICIPATION AND TRUST. PARTICIPATION WILL BE CRITICAL TO SECURE CENTER'S SUCCESS SINCE IT WILL USE EXPERT-GUIDED PARTICIPATORY DESIGN TO DEVELOP ITS SERVICES. IN PARTICIPATORY DESIGN, COMMUNITY MEMBERS WORK HAND-IN-HAND WITH THE CENTER'S EXPERTS, DESIGNERS & DEVELOPERS. EXPERTS GUIDE COMMUNITY MEMBERS TO IDENTIFY TOOLS & SERVICES THAT WILL HELP THE COMMUNITY ADDRESS PRESSING RESEARCH SECURITY CONCERNS. DESIGNERS AND DEVELOPERS THEN CREATE THOSE TOOLS FOR THE COMMUNITY TO USE AND REFINE. THE SECURE CENTER WILL BE COMMUNITY DESIGNED, COMMUNITY USED, COMMUNITY IMPROVED. IN ADDITION TO TOOLS, SECURE CENTER WILL GATHER OR DEVELOP AND SHARE BEST PRACTICES, TRAINING, ANALYSES, AND MORE. THROUGH THESE ACTIVITIES, SECURE CENTER WILL HELP RESEARCHERS MAKE RISK-INFORMED DECISIONS TO SAFEGUARD ONGOING AND FUTURE RESEARCH ACTIVITIES. RESEARCH SECURITY IS AN ONGOING CONCERN. TO SUPPORT THE RESEARCH COMMUNITY IN COMBATING MALIGN FOREIGN INFLUENCE, THIS PROJECT ESTABLISHES A NON-GOVERNMENTAL RESEARCH SECURITY ORGANIZATION, NAMED THE SECURE (SAFEGUARDING THE ENTIRE COMMUNITY OF THE U.S. RESEARCH ECOSYSTEM) CENTER. THE SECURE CENTER WILL BE A BRIDGE BETWEEN THE RESEARCH COMMUNITY AND GOVERNMENT FUNDING AGENCIES. REPRESENTATIVES FROM THESE AGENCIES COMPRISE THE U.S. GOVERNMENT STEERING COMMITTEE (USG SC), WHICH IS CHAIRED BY NSF. THE USG SC WILL ADVISE NSF ON RESEARCH SECURITY ISSUES THAT MAY IMPACT THE WORK OF SECURE CENTER, MAKE NSF AWARE OF NEW INFORMATION THAT MAY BE RELEVANT TO SECURE CENTER'S MISSION, AND COORDINATE THE DECLASSIFICATION OF INFORMATION TO BE SHARED BY NSF WITH SECURE CENTER FOR ULTIMATE DISSEMINATION TO THE U.S. RESEARCH COMMUNITY. THE RESEARCH COMMUNITY WILL PROVIDE GUIDANCE ON THE CENTER'S INTERNAL OPERATIONS, POLICIES, VISION, AND DIRECTION THROUGH THE ADVISORY BOARD, WHICH IS CHAIRED BY A NATIONAL SECURITY EXPERT, AND COMPOSED OF COMMUNITY REPRESENTATIVES FROM THE SPECTRUM OF ORGANIZATIONS THAT THE SECURE CENTER WILL SERVE. THE NATIONAL SECURE CENTER IS LED BY THE UNIVERSITY OF WASHINGTON (UW)'S CENTER ON COLLABORATIVE SYSTEMS FOR SECURITY, SAFETY, AND RESILIENCE (COSSAR) IN COLLABORATION WITH NINE ADDITIONAL INSTITUTIONS OF HIGHER EDUCATION (IHES) & THREE PRIVATE SECTOR ORGANIZATIONS. SIX IHES WILL LEAD FIVE REGIONAL CENTERS: - SECURE NORTHEAST -- NORTHEASTERN UNIVERSITY - SECURE SOUTHEAST -- EMORY UNIVERSITY - SECURE MIDWEST -- UNIVERSITY OF MISSOURI - SECURE SOUTHWEST -- UNIVERSITY OF TEXAS SAN ANTONIO AND TEXAS A&M UNIVERSITY - SECURE WEST -- UNIVERSITY OF WASHINGTON MISSISSIPPI STATE UNIVERSITY, THE UNIVERSITY OF MICHIGAN, AND STANFORD'S HOOVER INSTITUTION WILL PROVIDE CRITICAL SUBJECT MATTER EXPERTISE ON SENSITIVE RESEARCH, THREAT TYPES, GEOPOLITICAL ANALYSIS, AND INTERNATIONAL COOPERATION. THE COLLEGE OF CHARLESTON WILL LEAD EFFORTS TO INCLUDE EMERGING AND MINORITY-SERVING INSTITUTIONS (ERIS & MSIS) IN SECURE'S ACTIVITIES; THE UNIVERSITY OF MICHIGAN WILL ENSURE THAT SECURE'S SERVICES BALANCE THE NEED FOR COLLABORATION WITH THE NEED FOR PROTECTION. IMPULSION CONSULTING, INSIGHT GLOBAL, AND MINDCETTE WILL PROVIDE ADDITIONAL EXPERTISE TO THE CENTER AS IT UNDERTAKES A POWERFUL, PROVEN, PARTICIPATORY DESIGN PROCESS TO CO-CREATE THE SECURE SHARED VIRTUAL ENVIRONMENT (SVE) AND ITS SUITE OF OFFERINGS. AS THE FIRST OF ITS KIND, SECURE SVE WILL LINK MEMBERS OF THE U.S. RESEARCH COMMUNITY FROM IHES, NON-PROFITS, AND SMALL- & MEDIUM-SIZED BUSINESSES IN A SAFE, TRUSTWORTHY PLATFORM TO SHARE IDEAS, NEEDS, AND INFORMATION ON RESEARCH SECURITY. TRUST WILL ALSO BE FOSTERED THROUGH FIVE REGIONAL CENTERS, WHICH WILL FACILITATE CO-CREATION UNDER THE GUIDANCE OF THE NATIONAL CENTER. THIS APPROACH ENSURES THAT CO-CREATION IS RELEVANT TO ORGANIZATIONS THAT MAY EXIST IN VASTLY DIFFERENT GEOGRAPHIC, ADMINISTRATIVE, AND SOCIOECONOMIC CONTEXTS WHILE SIMULTANEOUSLY LEVERAGING THE DESIGN AND DEVELOPMENT CAPABILITIES OF UW'S COSSAR. THIS STRUCTURE ALSO ELEVATES REGIONAL CONCERNS TO A NATIONAL LEVEL WHERE ORGANIZATIONS MAY DISCOVER THAT THEIR CHALLENGES ARE SIMILAR IN UNEXPECTED WAYS, PAVING THE WAY FOR SOLUTIONS THAT MIGHT NOT OTHERWISE BE CONCEIVED. THE SECURE CENTER WILL BE COMMUNITY DESIGNED, COMMUNITY USED, COMMUNITY IMPROVED, DESIGNING A SUITE OF SOLUTIONS WILL INCLUDE BUT IS NOT LIMITED TO SHARED TOOLS, BEST PRACTICES, TRAINING, ANALYSES, AND OTHER INFORMATION, ALL DELIVERED THROUGH SECURE SVE TO ASSIST THE RESEARCH COMMUNITY IN MAKING DECISIONS REGARDING THEIR RESEARCH ACTIVITIES IN THE CONTEXT OF MALIGN FOREIGN THREATS. ADDITIONALLY, THE SECURE CENTER WILL BUILD CAPACITY IN PARTICIPATORY DESIGN THAT MAY HAVE THE POWER TO TRANSFORM THE WAY OTHER CHALLENGING ISSUES, SUCH AS ADMINISTRATIVE CAPACITY TO SECURE AND MANAGE FEDERAL RESEARCH FUNDING AT ERIS & MSIS, ARE ADDRESSED. 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.

MALARIA EVOLUTION IN SOUTH ASIA

SUSTAINING NANOOS, THE PACIFIC NORTHWEST COMPONENT OF THE US IOOS

GENE ACTION IN THE PATHOBIOLOGY OF AGING

SCALING UP VOLUNTARY MALE CIRCUMCISION TO PREVENT HIV TRANSMISSION IN ZIMBABWE

MEDICAL SCIENTIST TRAINING PROGRAM

WE HAVE ESTABLISHED THE COOPERATIVE INSTITUTE FOR CLIMATE, OCEAN, AND ECOSYSTEM STUDIES (CICOES), A CO-LOCATED, CONSORTIUM COOPERATIVE INSTITUTE THAT INCLUDES THE UNIVERSITY OF WASHINGTON, THE UNIVERSITY OF ALASKA FAIRBANKS, AND THE COLLEGE OF EARTH, OCEAN, AND ATMOSPHERIC SCIENCES AT OREGON STATE UNIVERSITY. THE CICOES RESEARCH INSTITUTE CO-LOCATES CICOES STAFF AT NOAA PARTNER LABORATORIES INCLUDING THE PACIFIC MARINE ENVIRONMENTAL LABORATORY (PMEL), THE ALASKA FISHERIES SCIENCE CENTER (AFSC), AND THE NORTHWEST FISHERIES SCIENCE CENTER (NWFSC). THE CONSORTIUM COMPONENT OF CICOES INCLUDES AFFILIATED FACULTY AND STAFF AT ALL PARTNER UNIVERSITIES WHO CONTRIBUTE INTELLECTUAL EXPERTISE, RESEARCH CAPACITY, TECHNOLOGICAL DEVELOPMENT, EDUCATION AND TRAINING OF POTENTIAL NEXT-GENERATION NOAA EMPLOYEES, AND CONDUCT PUBLIC EDUCATION AND OUTREACH. THE GEOGRAPHIC RANGE OF CICOES EXTENDS FROM THE OREGON-CALIFORNIA BORDER, THROUGH WASHINGTON STATE TO THE GULF OF ALASKA, BERING SEA, CHUKCHI SEA, AND BEAUFORT SEA. ADDITIONAL RESEARCH EFFORTS ARE CONDUCTED IN THE SOUTHERN AND EQUATORIAL REGIONS OF THE PACIFIC OCEAN AND IN THE ATLANTIC, INDIAN, AND SOUTHERN OCEANS. RESEARCH PROGRAMS AND PROJECTS DETAILED IN THIS PROPOSAL ILLUSTRATE THE CAPABILITY, CAPACITY, AND VISION OF CICOES AND THE ALIGNMENT WITH NOAAS MISSION, RESEARCH, AND EDUCATION OBJECTIVES. CICOES, IN PARTNERSHIP WITH NOAA AND OTHER AGENCIES, WILL CONDUCT AND COORDINATE INNOVATIVE, TRANS DISCIPLINARY RESEARCH GROUPED IN NINE THEMES: 1. CLIMATE AND OCEAN VARIABILITY, CHANGE AND IMPACTS 2. EARTH SYSTEMS AND PROCESSES 3. ENVIRONMENTAL CHEMISTRY AND OCEAN CARBON 4. MARINE ECOSYSTEMS: OBSERVATION, ANALYSIS, AND FORECASTS 5. OCEAN AND COASTAL OBSERVATIONS 6. ENVIRONMENTAL DATA SCIENCE 7. AQUACULTURE SCIENCE 8. HUMAN DIMENSIONS IN MARINE SYSTEMS 9. POLAR STUDIES THE PROPOSED RESEARCH AND RELATED ACTIVITIES BUILD ON THE 45+ YEARS OF RESEARCH, EDUCATION, AND OUTREACH LEADERSHIP BY THE JOINT INSTITUTE FOR THE STUDY OF THE ATMOSPHERE AND OCEAN (JISAO) AND NOW CICOES. WE WILL CONTINUE JOINT EFFORTS WITH OUR NOAA PARTNERS ON LONGSTANDING PROGRAMS AND EXPAND OUR RESEARCH PORTFOLIO IN COLLABORATION WITH NEW NOAA AND ACADEMIC PARTNERS TO CONDUCT AND COORDINATE TRANSFORMATIONAL RESEARCH, EXCEPTIONAL EDUCATION AND TRAINING, AND MEANINGFUL PUBLIC OUTREACH. CICOES PARTNERS WILL ALL CONTRIBUTE WORLD-CLASS TECHNOLOGIES, EXPERTISE, AND INFRASTRUCTURE TO THIS RESEARCH ENTERPRISE THAT HAS BEEN TAILORED TO ADDRESS THE THEMES OUTLINED IN THE 2019 NOTICE OF FUNDING OPPORTUNITY (NOFO). WE WILL CONTINUE TO MAINTAIN OUR INSTITUTIONAL FLEXIBILITY TO ENABLE ALL NOAA AND UNIVERSITY PARTNERS TO ADAPT TO EVOLVING RESEARCH PRIORITIES AND OPPORTUNITIES AS THEY ARISE.

CREATING COMPREHENSIVE MAPS OF WORM AND FLY TRANSCRIPTION FACTOR BINDING SITES

COMPREHENSIVE BIOLOGY: EXPLOITING THE YEAST GENOME

THE PURPOSE OF THIS COOPERATIVE AGREEMENT IS TO FUND RESEARCH TO THE RECIPIENT TO CARRY OUT A PUBLIC PURPOSE OF SUPPORT OR STIMULATION OF THE DEFENSE ADVANCED RESEARCH PROJECTS AGENCY DARPA DEFENSE SCIENCES OFFICE DSO AUTONOMOUS DIAGNOSTICS TO ENABLE PREVENTION AND THERAPEUTICS DIAGNOSTICS ON DEMAND LIMITED RESOURCE SETTINGS ADEPT DXOD LRS PROGRAM.

CENTER FOR ENABLING NEW TECHNOLOGIES THROUGH CATALYSIS (CENTC) PHASE II RENEWAL

CLINICAL NUTRITION RESEARCH UNIT

UW CENTER FOR MENDELIAN GENOMICS

AI INSTITUTE IN DYNAMIC SYSTEMS

THE LIFE CENTER: LEARNING IN INFORMAL AND FORMAL ENVIRONMENTS

TECHNICAL ASSISTANCE IN SUPPORT OF CLINICAL TRAINING AND MENTORING FOR HIV TREATM

INSTITUTE FOR NUCLEAR THEORY

TO STUDY IN DETAIL THE ASSOCIATION OF ATHEROSCLEROSIS, CLINICAL CARDIOVASCULAR DISEASE, AND LONG-TERM EXPOSURE TO AMBIENT PARTICULATE MATTER AND OTH

CLINICAL TRIALS NETWORK: PACIFIC NORTHWEST NODE

CENTER FOR THE MULTIPLEXED ASSESSMENT OF PHENOTYPE

CENTRAL HUB FOR KIDNEY PRECISION MEDICINE

SELF RENEWAL AND DIFFERENTIATION OF EMBRYONIC STEM CELLS

UW SHIP OPERATIONS, MAINTENANCE, REPAIR, AND UPGRADES 2023-2028

CENTER ON MATERIALS AND DEVICES FOR INFORMATION TECHNOLOGY RESEARCH

GRADUATE RESEARCH FELLOWSHIP PROGRAM

NATHAN SHOCK CTR OF EXCELLENCE IN BASIC BIOLOGY OF AGING

IMMUNOBIOLOGY AND IMMUNE THERAPY FOR MERKEL CELL CARCINOMA

CSSAS: THE CENTER FOR THE SCIENCE OF SYNTHESIS ACROSS SCALES

RURAL INITIATIVE IN STEM EDUCATION AND UNDERGRADUATE PREPARATION (RISE UP) GEAR UP PARTNERSHIP

AIDS EDUCATION TRAINING CENTERS

SUSTAINING NANOOS, THE PACIFIC NORTHWEST COMPONENT OF THE US IOOS

INTERDISCIPLINARY TRAINING IN GENOMIC SCIENCES

HDR INSTITUTE: ACCELERATED AI ALGORITHMS FOR DATA-DRIVEN DISCOVERY

RESEARCH IN MENTAL RETARDATION AND CHILD DEVELOPMENT

HUMAN RESOURCES FOR HEALTH (HRH) TO ACHIEVE AND SUSTAIN HIV/TB EPIDEMIC CONTROL IN MALAWI UNDER THE PRESIDENT'S EMERGENCY PLAN FOR AIDS RELIEF (PEPFAR)

VISION RESEARCH CENTER (CORE) - P30

MRSEC: UW MOLECULAR ENGINEERING MATERIALS CENTER

MALE CONTRACEPTION RESEARCH CENTER GRANT

UW ALACRITY CENTER FOR PSYCHOSOCIAL INTERVENTIONS RESEARCH

NEXT GENERATION TRANSLATIONAL PROTEOMICS FOR ALZHEIMER'S AND RELATED DEMENTIAS

GENETIC INSTABILITY IN WERNER SYNDROME

UNIVERSITY OF WASHINGTON MENDELIAN GENOMICS RESEARCH CENTER (UW-MGRC) - PROJECT SUMMARY/ABSTRACT THE GENETIC BASIS OF >2,920 MENDELIAN CONDITIONS (MCS) REMAINS UNKNOWN, AND HUNDREDS OF NOVEL MCS ARE DESCRIBED EACH YEAR. OUR GROUP HAS, IN PARTNERSHIP WITH 2,379 INVESTIGATORS FROM 656 INSTITUTIONS IN 55 COUNTRIES, ASSESSED 15,387 SAMPLES FROM 5,675 FAMILIES AND HAS, OVER THE PAST DECADE, IDENTIFIED GENES FOR 1379 MCS, INCLUDING 915 NOVEL DISCOVERIES. THE TRANSLATION AND IMPACT OF THESE DISCOVERIES ON DIAGNOSTICS AND CLINICAL CARE HAS BEEN IMMEDIATE AND SUBSTANTIAL. ADDITIONALLY, WE HAVE DEVELOPED MULTIPLE NEW ANALYTICAL TOOLS INCLUDING CADD, PRIMUS, CONIFER, SMRT-SV, RV-TDT, AS WELL AS METHODOLOGICAL INNOVATIONS INCLUDING MIPS, SMMIPS, AND APPROACHES FOR LOW INPUT EXOME AND GENOME SEQUENCING (ES/WGS). WE ARE ALSO DEEPLY COMMITTED TO OPEN DATA SHARING WITH ROLLING SUBMISSION OF EXOME AND GENOME DATA TO THE ANVIL (1,439 DEPOSITED); DEVELOPMENT OF A MATCHMAKER EXCHANGE NODE (HTTP://MYGENE2.ORG) THAT ENABLES PUBLIC SHARING OF GENOTYPE AND PHENOTYPIC DATA AMONG FAMILIES, RESEARCHERS, AND CLINICIANS; AND CREATION OF A PUBLIC DATA BROWSER (HTTP://GENO2MP.GS.WASHINGTON.EDU) THAT LINKS DE-IDENTIFIED, INDIVIDUAL-LEVEL GENOTYPES FROM OVER 18,000 EXOMES/GENOMES TO INDIVIDUAL PHENOTYPES. IN THIS APPLICATION, WE BUILD UPON THESE SUCCESSES TO ESTABLISH THE UNIVERSITY OF WASHINGTON MENDELIAN GENOMICS RESEARCH CENTER (UW-MGRC) WITH THE OVERARCHING GOAL TO MAXIMIZE NOVEL GENE DISCOVERY FOR MCS, WITH AN EMPHASIS ON CANONICAL MCS THAT HAVE GONE UNSOLVED USING ES/WGS, AND NONCODING VARIANTS UNDERLYING MCS. TO THIS END, WE WILL DEVELOP NOVEL APPROACHES TO INFORM VARIANT INTERPRETATION AND FUNCTIONAL VALIDATION FOR THE HUMAN GENETICS COMMUNITY AT-LARGE AND DISSEMINATE RESULTS, DATA, AND TOOLS OPENLY. WE WILL CAPITALIZE ON IMMEDIATE ACCESS TO SEQUENCE-READY SAMPLES FROM ~300 MCS (>26,000 SAMPLES), 1,500 SAMPLES SUSPECTED OF HARBORING A CAUSAL NONCODING VARIANT FOR A MC, AND AN AGGRESSIVE SAMPLE SOLICITATION PLAN IN PARTNERSHIP WITH INDUSTRY, ACADEMIC CENTERS, AND OTHER NIH PROGRAMS. WE PROPOSE THREE SPECIFIC AIMS: (1) MAXIMIZE NOVEL GENE DISCOVERY FOR MCS BY SOLICITATION, SEQUENCING, AND ANALYSIS OF FAMILIES WITH UNEXPLAINED (I.E., NO KNOWN UNDERLYING GENE) MCS; CLASSIC MCS CONSIDERED HIGH PRIORITY BY THE CLINICAL GENETICS COMMUNITY AND THAT HAVE BEEN RECALCITRANT TO GENE DISCOVERY EFFORTS; AND CASES THAT REMAIN UNSOLVED AFTER PRIOR EXOME OR GENOME SEQUENCING. (2) DEVELOP NEW STRATEGIES FOR GENE DISCOVERY FOR UNSOLVED MCS CAUSED BY VARIANTS THAT ARE DIFFICULT TO DETECT OR OF UNKNOWN FUNCTIONAL EFFECTS (E.G., STRUCTURAL VARIANTS, REPEAT EXPANSIONS, CRYPTIC SPLICE, REGULATORY, ETC.), AND/OR UNUSUAL MODES OF INHERITANCE, AND, IN DOING SO, CHARACTERIZE THE GENETIC ARCHITECTURE OF PATHOGENIC NONCODING VARIANTS UNDERLYING MCS. IMPLEMENT HIGH- THROUGHPUT SCREENING AND TARGETED FOLLOW-UP FUNCTIONAL STUDIES TO PRIORITIZE AND VALIDATE ASSERTIONS OF PATHOGENICITY OF CANDIDATE NONCODING VARIANTS. (3) TAKE A LEADERSHIP ROLE TO OPENLY AND PUBLICLY, WHEN FEASIBLE, SHARE SEQUENCING AND RICH PHENOTYPIC METADATA, METHODS, AND KNOWLEDGE, TO EMPOWER INVESTIGATORS WORLDWIDE AND ACCELERATE THE PACE OF GENE DISCOVERY.

CENTER FOR ENABLING NEW TECHNOLOGIES THROUGH CATALYSIS

SYSTEM FOR ADVANCED BIOFUELS PRODUCTION FROM WOODY BIOMASS IN THE PACIFIC NORTHWEST

CYTOMEGALOVIRUS (CMV) VACCINE IN?ORTHOTOPIC?LIVER?TRANSPLANT CANDIDATES (COLT) - PROJECT SUMMARY : CYTOMEGALOVIRUS (CMV) HAS A MAJOR NEGATIVE IMPACT IN SOLID ORGAN TRANSPLANT RECIPIENTS (SOTXR) DUE TO LIMITATIONS IN CURRENT PREVENTIVE AND THERAPEUTIC STRATEGIES, ESPECIALLY IN CMV SERONEGATIVE RECIPIENTS (R-) OF ORGANS FROM SEROPOSITIVE DONORS (D+) [D+R-]. THE D+R- SUBSET COMPRISES ~25% OF ALL SOTXR BUT >80% OF CMV DISEASE AND IS INDEPENDENTLY ASSOCIATED WITH WORSE LONG-TERM SURVIVAL AFTER SOTX. THE DISPROPORTIONATE IMPACT IN D+R- SOTXR RESULTS FROM AN IMPAIRED ABILITY TO DEVELOP A PRIMARY IMMUNE RESPONSE TO DONOR-TRANSMITTED CMV INFECTION IN THE CONTEXT OF IMMUNOSUPPRESSION. STRATEGIES THAT ELICIT OR ENHANCE CMV-SPECIFIC IMMUNITY PRIOR TO SOTX COULD LEAD TO MORE EFFECTIVE PREVENTION/CONTROL OF CMV AFTER SOTX, MINIMIZING THE NEED FOR TOXIC CMV ANTIVIRAL THERAPY (AVT). WE HAVE DEVELOPED A MODIFIED VACCINIA ANKARA VIRUS VACCINE, TRIPLEX, THAT EXPRESSES IMMUNODOMINANT CMV ANTIGENS PP65, IE-1, AND IE-2 THAT ARE TARGETS OF PROTECTIVE T CELL IMMUNITY. TRIPLEX ELICITS ROBUST, LONG-LASTING, AND FUNCTIONAL CMV-SPECIFIC CD4 AND CD8 T CELLS. TRIPLEX WAS SAFE, ACCELERATED RECONSTITUTION OF CMV PROTECTIVE IMMUNITY, AND REDUCED SIGNIFICANT CMV INFECTION BY ~50% IN A PHASE 2 STUDY OF ALLOGENEIC HEMATOPOIETIC CELL TXR. OUR LONG-TERM GOALS ARE TO HARNESS VACCINE-INDUCED CMV- SPECIFIC CELLULAR IMMUNITY TO REDUCE THE IMPACT OF CMV IN D+R- SOTXR AND TO DEFINE IMMUNE CORRELATES OF RISK (COR) AND FOR PROTECTION (COP) (I.E. IMMUNE CORRELATES OF TRIPLEX VACCINE EFFICACY [VE]). THE CENTRAL HYPOTHESIS IS THAT PRE-TX TRIPLEX VACCINATION OF CMV SERONEGATIVE LTX CANDIDATES ELICITS FUNCTIONAL CMV-SPECIFIC CD4 AND CD8 T CELLS, LEADING TO IMPROVED IMMUNE CONTROL OF CMV AND SIGNIFICANTLY DECREASES THE NEED FOR CMV AVT POST- TX IN D+R- LTXR WHO RECEIVE PREEMPTIVE THERAPY (PET) FOR CMV PREVENTION. WE FURTHER HYPOTHESIZE THAT THERE ARE SPECIFIC IMMUNE COR FOR CMV OUTCOMES AND COP OF TRIPLEX VACCINE. WE WILL LEVERAGE OUR ESTABLISHED CONSORTIUM AND PRELIMINARY STUDIES IN A TARGET POPULATION OF D+R- LTXR WITH HIGH UNMET NEED (NO FDA-APPROVED AVAILABLE ANTIVIRAL PROPHYLAXIS OPTIONS, HIGHLY SUSCEPTIBLE TO VALGANCICLOVIR TOXICITY, AND SIGNIFICANT CMV- ASSOCIATED MORBIDITY, MORTALITY, AND COST). THE OBJECTIVES OF THIS PROPOSAL ARE TO ASSESS THE EFFICACY, SAFETY AND IMMUNOGENICITY OF TRIPLEX IN D+R- LTXR IN A PHASE 2 STUDY AND TO DEFINE THE IMMUNE COR AND COP USING STATE- OF-THE-ART POLYFUNCTIONAL T CELL ASSAYS AND NOVEL ANALYTIC APPROACHES (COMBINATORIAL POLYFUNCTIONALITY ANALYSIS OF ANTIGEN-SPECIFIC T CELL SUBSETS [COMPASS]). AN EFFECTIVE PRE-TX CMV VACCINATION APPROACH WOULD TRANSFORM CMV PREVENTION STRATEGIES IN SOTX. THE PROPOSED STUDIES WILL DEFINE IMMUNE COR FOR CLINICAL OUTCOMES, WHICH WILL FACILITATE EFFICIENT EVALUATION OF FUTURE IMMUNE-BASED STRATEGIES, AND LEAD TO BROADER IMPLEMENTATION OF THE MORE EFFECTIVE PET CMV PREVENTION STRATEGY IN D+R- LTXR.

UNIVERSITY TRANSPORTATION CENTERS

UW CENTER FOR MENDELIAN GENOMICS

AIDS EDUCATION AND TRAINING CENTERS PROGRAM

TARGETED LONG-ACTING COMBINATION ANTIRETROVIRAL THERAPY (TLC-ART)

UNIVERSITY OF WASHINGTON (UW) MENDELIAN GENOMICS DATA COORDINATING CENTER - PROJECT SUMMARY DESPITE SIGNIFICANT ADVANCES MADE IN UNDERSTANDING THE GENETIC BASIS OF THE MORE THAN 10,000 ESTIMATED MENDELIAN CONDITIONS IN RECENT DECADES, FURTHER SCIENTIFIC COLLABORATION AND DISCOVERY IS REQUIRED TO IDENTIFY THE FULL SET OF MENDELIAN DISEASES AND THEIR UNDERLYING GENETIC CAUSES. TO BUILD ON THE SUCCESS OF THE CENTERS FOR MENDELIAN GENOMICS BY USING FURTHER TECHNOLOGICAL, METHODOLOGICAL, AND DATA-SHARING INNOVATIONS, NHGRI IS ESTABLISHING A NEW MENDELIAN GENOMICS RESEARCH CONSORTIUM. AS DATA COORDINATING CENTER FOR THIS CONSORTIUM, WE PROPOSE TO FURTHER THE DISCOVERY AND CHARACTERIZATION OF MENDELIAN CONDITIONS BY ACHIEVING FOUR MAIN AIMS. (1) MANAGING THE RELEASE OF MOLECULAR AND PHENOTYPIC DATA GENERATED OR COLLECTED BY THE CONSORTIUM'S RESEARCH CENTERS, FEATURING SEMI-AUTOMATED AND SCALABLE QUALITY CONTROL PROCEDURES THAT WILL VALIDATE INCOMING DATA AGAINST COLLABORATIVELY-ESTABLISHED STANDARDS AND REQUIREMENTS. WE WILL FACILITATE DATA SHARING WITHIN THE CONSORTIUM AND THE BROADER SCIENTIFIC COMMUNITY BY ENSURING THAT CURATED DATA ARE SUBMITTED TO APPROPRIATE REPOSITORIES INCLUDING ANVIL, CLINVAR, AND MATCHMAKER EXCHANGE. (2) SUPPORTING PROGRAM OUTREACH THROUGH A CONSORTIUM WEBSITE THAT HIGHLIGHTS PROGRAM PROGRESS AND DISCOVERIES AND ENABLING CONNECTIONS AMONG RESEARCHERS, CLINICIANS, AND FAMILIES. WE WILL ALSO OVERSEE EDUCATION, TRAINING, AND MENTORSHIP OPPORTUNITIES. (3) COORDINATING LOGISTICS FOR THE CONSORTIUM, INCLUDING ORGANIZATION OF VIRTUAL AND IN-PERSON MEETINGS AND ADMINISTRATIVE SUPPORT FOR ALL CONSORTIUM-WIDE ACTIVITIES. (4) OVERSEEING AN OPPORTUNITY FUND, ADMINISTERING UP TO 5 AWARDS IN EACH OF YEARS 2-5 OF THE CONSORTIUM, TO SUPPORT NOVEL AND SCALABLE APPROACHES TO FUNCTIONAL FOLLOW-UP ON CANDIDATE VARIANTS. TO ACHIEVE THESE FOUR MAIN AIMS, WE PROPOSE INNOVATIVE APPROACHES, INCLUDING LEVERAGING EMERGING CLOUD-BASED SYSTEMS FOR THE STORAGE AND ANALYSIS OF HUMAN GENETIC DATA AND INTEGRATING INTERNATIONAL DATA SHARING STANDARDS TO ENSURE THAT DATA IS FINDABLE, ACCESSIBLE, INTEROPERABLE, AND REUSABLE (FAIR). FURTHERMORE, WE BRING A UNIQUE BLEND OF EXPERTISE ACROSS THE FIELDS OF DATA SCIENCE, CLOUD SYSTEMS, BIOSTATISTICS, BIOETHICS, CLINICAL GENETICS, AND MENDELIAN DISCOVERY TO THE CONSORTIUM, AND OUR APPLICATION RESTS ON 13 SUCCESSFUL YEARS OF EXPERIENCE AND EXPERTISE SERVING AS COORDINATING OR ANALYSIS CENTERS FOR 7 LARGE-SCALE GENETIC AND BIOMEDICAL PROJECTS. THROUGH SUPPORT AND COORDINATION OF THIS CONSORTIUM, WE WILL HELP YIELD THE BENEFITS OF IDENTIFYING THE GENETIC BASIS OF MENDELIAN CONDITIONS TO SUPPORT DIAGNOSIS, THERAPY, AND FURTHER DELINEATION OF SYNDROMES. FURTHER PUBLIC HEALTH BENEFIT WILL ACCRUE VIA BIOLOGICAL INSIGHTS INTO MENDELIAN DISEASES THAT ALSO ADVANCE OUR UNDERSTANDING OF RELATED COMMON, COMPLEX DISEASES.

INTEGRATED NEXT-GENERATION SURVEILLANCE IN GLOBAL HEALTH: TRANSLATION TO ACTION (INSIGHT TO ACTION)

HIV SURVEILLANCE FOR EPIDEMIC CONTROL IN MALAWI UNDER THE PRESIDENT?S EMERGENCY PLAN FOR AIDS RELIEF (PEPFAR) - THE UNITED STATES PRESIDENT’S EMERGENCY PLAN FOR AIDS RELIEF (PEPFAR) RELIES ON DATA TO GUIDE PROGRAMMATIC PRIORITIES AND ACTIVITIES FOR HIV EPIDEMIC CONTROL IN LOW- AND MIDDLE-INCOME COUNTRIES. IT IS CRUCIAL THAT UP-TO-DATE QUALITY SURVEILLANCE DATA ARE AVAILABLE FOR EVIDENCE-BASED PLANNING. IN RESPONSE TO THE CENTERS OF DISEASE CONTROL FUNDING OPPORTUNITY CDC-RFA-GH22-2248, I-TECH HAS FORMED A CONSORTIUM WITH LOCAL PARTNERS CALLED THE MALAWI SURVEILLANCE AND EPIDEMIC PREPAREDNESS PARTNERSHIP (MSEPP) TO ADDRESS THIS NEED. MSEPP MEMBERS INCLUDE I-TECH, THE MALAWI AIDS COUNSELLING AND RESOURCE ORGANIZATION (MACRO), KAMUZU UNIVERSITY OF HEALTH SCIENCES (KUHES) AND MALAWI BLOOD TRANSFUSION SERVICES (MBTS), WITH I-TECH SERVING AS THE PRIME. MSEPP STRATEGIES AND ACTIVITIES WILL BUILD THE CAPACITY OF THE MALAWI MINISTRY OF HEALTH (MOH) AND THE PUBLIC HEALTH INSTITUTE OF MALAWI (PHIM) TO IMPLEMENT EFFECTIVE SURVEILLANCE SYSTEMS IN LINE WITH INTERNATIONAL STANDARDS TO RESPOND TO CURRENT AND NEW DISEASES. CAPACITY BUILDING WILL BE THROUGH ON-THE-JOB TRAINING, APPLIED LEARNING EXPERIENCES, COLLABORATION ON THE DESIGN AND IMPLEMENTATION OF ESSENTIAL AND TIMELY SURVEILLANCE STUDIES, AND SECONDING STAFF. SECONDED STAFF, REFERRED TO AS TECHNICAL ASSISTANTS (TAS) WILL SUPPORT PHIM AND MOH THROUGH GENERAL ORGANIZATIONAL AND MANAGEMENT SUPPORT ACTIVITIES, SUCH AS REVIEWING AND PROVIDING STRATEGIC SUPPORT FOR IMPLEMENTATION OF PHIM’S STRATEGIC PLAN, SUPPORTING DEVELOPMENT OF GUIDELINES AND STANDARD OPERATING PROCEDURES (SOPS) FOR ORGANIZATIONAL CAPACITY DEVELOPMENT AND FIELD ACTIVITIES, SUPPORTING COORDINATION OF PHIM TECHNICAL WORKING GROUP MEETINGS, AND FACILITATING EXECUTION OF ACTIONS POINTS RESULTING FROM SUCH MEETINGS. MSEPP WILL PARTNER WITH PHIM FOR DIRECT IMPLEMENTATION OF SURVEILLANCE ACTIVITIES UNTIL CAPACITY IS BUILT AND TRANSITION ACHIEVED. WITHIN THE FIRST YEAR OF THE AWARD, I-TECH WILL HOLD PLANNING MEETINGS WITH PHIM, MOH, AND CDC TO DEVELOP A ROA D MAP WITH BENCHMARKS FOR GUIDING A GRADUAL BUT STEADY TRANSITION OF MOST OF THE SURVEILLANCE ACTIVITIES TO PHIM AND MOH BY THE END OF THE GRANT PERIOD. THE TRANSITION PLAN WILL BE MONITORED AND DISCUSSED ANNUALLY WITH PHIM, MOH, AND CDC TO ENSURE ANY NECESSARY MODIFICATIONS TO THE PLAN AND/OR CAPACITY BUILDING APPROACH ARE MADE.

TRIGLYCERIDES, DIABETES AND CARDIOVASCULAR DISEASE

INSTITUTE OF TRANSLATIONAL HEALTH SCIENCES

STEM CELLS AND CARDIOVASCULAR REPAIR

RURAL INITIATIVE IN STEM EDUCATION AND UNDERGRADUATE PREPARATION (RISE UP) GEAR UP PARTNERSHIP

UNIVERSITY OF WASHINGTON SEXUALLY TRANSMITTED INFECTIONS COOPERATIVE RESEARCH CEN

HEALTH PROMOTION RESEARCH CENTER

IMMUNOLOGY AND VIROLOGY OF ACUTE HIV INFECTION

THE COMMUNITY YOUTH DEVELOPMENT STUDY: A TEST OF COMMUNITIES THAT CARE

STEM CELL GENE THERAPY FOR HEMOGLOBINOPATHIES

NORTHWEST GENOMICS CENTER

NANOPORE SEQUENCING OF DNA WITH MSPA

BIOMEDICAL AND HEALTH INFORMATICS TRAINING PROGRAM

LABORATORY OF DEVELOPMENTAL BIOLOGY

WASHINGTON SEA GRANT PROGRAM PLAN FOR RENEWAL OF SEA GRANT COLLEGE SUPPORT, 2010 - 2014

SUSTAINING NANOOS, THE PACIFIC NORTHWEST COMPONENT OF THE US IOOS

WASHINGTON SEA GRANT PROGRAM PLAN FOR RENEWAL OF SEA GRANT COLLEGE SUPPORT 2014 - 2018

THE ELECTRONIC MEDICAL RECORDS AND GENOMICS (EMERGE) NETWORK, PHASE III

GH11-1191 IMPROVEMENT OF INTERGRATED HIV CLINICAL-BASED SERVICES

HEALTH PROMOTION AND DISEASE PREVENTION RESEARCH CENTER

STD/AIDS RESEARCH TRAINING GRANT

NORTHERN/PACIFIC UNIVERSITIES GLOBAL HEALTH RESEARCH TRAINING CONSORTIUM

HOST PATHOGEN VARIATION & TB PATHOGENESIS - HURDLES FOR CONTROLLING TUBERCULOSIS (TB) INCLUDE DEVELOPING A HIGHLY EFFICACIOUS VACCINE, PREVENTING TRANSMISSION AND INFECTION IN ENDEMIC AREAS, AND DISCOVERING DRUG TREATMENT REGIMENS THAT WORK RAPIDLY AND KILL DORMANT BACILLI WITHIN MACROPHAGES. AFTER EXPOSURE TO MYCOBACTERIUM TUBERCULOSIS (MTB), OUTCOMES VARY WIDELY INCLUDING RESISTANCE, ASYMPTOMATIC LATENT INFECTION, ACTIVE PULMONARY DISEASE, AND DISSEMINATED INFECTIONS INCLUDING TB MENINGITIS (TBM). THIS HETEROGENEITY COMPLICATES CLINICAL TREATMENT DECISIONS WITH REGARDS TO CHOOSING THE NUMBER OF DRUGS AND DURATION OF TREATMENT. THIS BROAD CLINICAL SPECTRUM ALSO PRESENTS A UNIQUE OPPORTUNITY FOR UNDERSTANDING THE BIOLOGICAL MECHANISMS THAT CONTROL TB PATHOGENESIS. A MAJOR SOURCE OF HETEROGENEITY IS A COMBINATION OF GENETIC VARIATION IN BOTH HUMANS AND MTB THAT ARE EVOLVING UNDER CONSTANT SELECTIVE PRESSURE. OUR OVERALL PROGRAM OBJECTIVE IS TO USE GENETIC, GENOMIC, PROTEOMIC, AND BIOINFORMATIC STRATEGIES TO DISCOVER HOST AND PATHOGEN VARIANTS OF GENES AND GENE PRODUCTS THAT ARE ASSOCIATED WITH TB CLINICAL OUTCOMES AND TO DETERMINE HOW THESE VARIANTS INTERACT TO REGULATE MOLECULAR, CELLULAR, AND IN VIVO FUNCTIONS. OUR STRATEGY IS ANCHORED UPON TWO POWERFUL COHORTS IN VIETNAM AND UGANDA (CORE A) THAT CAPTURE THE FULL SPECTRUM OF RESISTANCE TO TRADITIONAL LTBI (LATENT TB INFECTION), LTBI, PULMONARY TB DISEASE, AND DISSEMINATED DISEASE IN THE FORM OF TBM. CORE A EXAMINES PAIRED HOST AND MTB GENETIC DATA AND THE ASSOCIATION WITH THESE DIVERSE CLINICAL OUTCOMES. IN PROJECT 1, WE USE GENETIC AND NEW PROTEOMIC STRATEGIES TO EXAMINE HOW THE MTB GENES AND VARIANTS IDENTIFIED BY CORE A FUNCTION AND HOW THE ENCODED PROTEINS INTERACT WITH AND REGULATE MACROPHAGE RESPONSES. IN PROJECT 2, WE USE HUMAN GENETIC METHODS ALONG WITH PROTEOMIC STRATEGIES IN MACROPHAGES TO UNCOVER REGULATORY HOST GENES AND VARIANTS THAT ARE ASSOCIATED WITH RESISTANCE TO MTB INFECTION AND/OR DISSEMINATED TB. IN PROJECT 3, WE EXAMINE IN VIVO MECHANISMS OF TRANSMISSION AND DISSEMINATION THAT ARE ATTRIBUTED TO SPECIFIC HOST GENES AND PATHWAYS AND MTB VARIANTS, EMPLOYING A NEW AND POWERFUL MOUSE MODEL OF INFECTION THAT RECAPITULATES MANY OF THE MANIFESTATIONS THAT OCCUR IN HUMAN TB. CORE B USES PATHWAY-DRIVEN AND NOVEL BIOINFORMATICS APPROACHES TO INTEGRATE THE GENETIC RESULTS FROM CORE A WITH THE MULTIPLE LARGE-SCALE AND DIVERSE DATASETS TO DYNAMICALLY IDENTIFY AND PRIORITIZE PATHWAYS AND PROTEIN NETWORKS FOR FUNCTIONAL TESTING. TOGETHER, THIS MULTIDISCIPLINARY PROGRAM AND STRATEGY WILL ENABLE US TO TEST OUR OVERALL HYPOTHESIS THAT VARIANTS OF MTB AND HOST GENES DICTATE HETEROGENEOUS CLINICAL OUTCOMES AND ENCODE FACTORS THAT INTERACT WITH AND ALTER INNATE IMMUNE CELLS. WE WILL USE GENETIC, GENOMIC, PROTEOMIC, AND BIOINFORMATIC STRATEGIES TO EXAMINE VARIATION IN MTB AND ITS PAIRED HUMAN HOST TO EXAMINE MECHANISMS OF RESISTANCE AND SUSCEPTIBILITY TO INFECTION AND DISEASE WITH DISCOVERY OF BIOMARKERS FOR CLINICAL MANAGEMENT AND NOVEL IMMUNOMODULATORY THERAPIES.

SURFACE ANALYSIS FACILITY FOR BIOMEDICAL PROBLEMS

TRAINING IN MOLECULAR AND CELLULAR BIOLOGY

COMPUTATIONAL AND CIRCUIT MECHANISMS UNDERLYING RAPID LEARNING

WELLSTONE MUSCULAR DYSTROPHY SPECIALIZED RESEARCH CENTER (SEATTLE)

MECHANISMS OF DRUG DISPOSITION DURING PREGNANCY

A COMPREHENSIVE CATALOG OF HUMAN DNASEL HYPERSENSITIVE SITES

FRC TRANSLATION, CONFINEMENT, AND SUSTAINMENT STUDIES (TCSS)

TRAINING IN CANCER BIOLOGY AND TRANSPLANTATION

STRUCTURE-BASED DESIGN OF BROADLY PROTECTIVE CORONAVIRUS VACCINES - PROJECT SUMMARY – OVERALL: STRUCTURE-BASED DESIGN OF BROADLY PROTECTIVE CORONAVIRUS VACCINES WE PROPOSE A HIGHLY SYNERGISTIC RESEARCH PROGRAM FOCUSED ON DEVELOPING TWO BROADLY PROTECTIVE CORONAVIRUS VACCINE CANDIDATES: A PAN-SARBECOVIRUS VACCINE AT THE END OF YEAR 2, AND A PAN-BETACORONAVIRUS AT THE END OF YEAR 5. OUR PROGRAM BRINGS TOGETHER SIX RESEARCH GROUPS WITH COMPLEMENTARY AND SYNERGISTIC EXPERTISE IN STRUCTURE-BASED VACCINE DESIGN, CORONAVIRUS STRUCTURAL BIOLOGY AND IMMUNITY, THE IMMUNOLOGY OF VACCINES, ANIMAL MODEL DEVELOPMENT, AND VIRAL EVOLUTION. THIS TEAM EMERGED IN RESPONSE TO THE SARS-COV-2 PANDEMIC TO RAPIDLY DEVELOP AN ULTRAPOTENT PROTEIN NANOPARTICLE VACCINE THAT IS CURRENTLY IN PHASE I/II CLINICAL TRIALS, WITH FUNDING SECURED FOR PHASE III. OUR PROGRAM COMPRISES THREE SCIENTIFIC PROJECTS SUPPORTED BY FOUR SCIENTIFIC CORES AND AN ADMINISTRATIVE CORE. THIS STRUCTURE WILL ALLOW MAXIMAL SYNERGY BETWEEN OUR GROUPS IN PURSUIT OF THE THREE CENTRAL OUTPUTS OF OUR PROGRAM: TOOLS, ANTIBODIES, AND VACCINES. TOOLS: WE WILL DEVELOP REVERSE GENETIC PLATFORMS FOR PRODUCING PANELS OF WILD-TYPE AND INDICATOR VIRUSES AND NEW ANIMAL MODELS OF HUMAN CORONAVIRUS DISEASE THAT CAN BE USED TO ASSESS NEUTRALIZING AND PROTECTIVE BREADTH. WE WILL ALSO DEVELOP PLATFORMS FOR DEEP MUTATIONAL SCANNING OF SPIKE PROTEINS SPANNING THE BETACORONAVIRUS PHYLOGENY TO INFORM ANTIGEN DESIGN AND MODEL DEVELOPMENT AND ASSESS THE BREADTH AND MUTATIONAL RESISTANCE OF VACCINE-ELICITED ANTIBODIES. ANTIBODIES: OUR PROGRAM WILL IDENTIFY CONSERVED EPITOPES IN BETACORONAVIRUS SPIKE PROTEINS TARGETED BY CROSS-REACTIVE ANTIBODIES, AND CHARACTERIZE THE STRUCTURAL BASIS FOR BROAD NEUTRALIZATION AND PROTECTION AT HIGH RESOLUTION. THIS INFORMATION WILL BE USED TO ITERATIVELY INFORM STRUCTURE-BASED ANTIGEN AND VACCINE DESIGN AND WILL GENERATE ANTIBODY THERAPEUTICS THAT COULD BLUNT THE EFFECTS OF FUTURE ZOONOTIC SPILLOVERS. VACCINES: WE RECENTLY SHOWED THAT CO-DISPLAYING MULTIPLE HEMAGGLUTININ ANTIGENS ON THE SAME SELF-ASSEMBLING PROTEIN NANOPARTICLE, AN APPROACH TERMED MOSAIC NANOPARTICLE DISPLAY, INDUCED BROADLY PROTECTIVE HUMORAL IMMUNITY AGAINST INFLUENZA. WE WILL COMBINE THIS APPROACH WITH CUTTING-EDGE COMPUTATIONAL METHODS FOR STABILIZING GLYCOPROTEIN ANTIGENS AND DESIGNING NANOPARTICLE SCAFFOLDS TAILORED TO DISPLAY CORONAVIRUS SPIKES IN OPTIMAL GEOMETRIES. WE EXPECT THE RESULTANT NANOPARTICLE VACCINE CANDIDATES TO ELICIT POTENT AND BROADLY PROTECTIVE ANTIBODY RESPONSES AGAINST CONSERVED EPITOPES IN BETACORONAVIRUS SPIKES. WE WILL MECHANISTICALLY AND FUNCTIONALLY EVALUATE THE PERFORMANCE OF THESE VACCINE CANDIDATES FORMULATED WITH CLINICALLY RELEVANT ADJUVANTS IN RELEVANT ANIMAL MODELS, INCLUDING NONHUMAN PRIMATES. TO FACILITATE SUCCESSFUL TRANSFER TO INDUSTRY PARTNERS, WE WILL PREPARE TECHNOLOGY TRANSFER PACKAGES FOR THE TWO LEAD VACCINE CANDIDATES THAT WILL BE PRODUCED BY OUR PROGRAM: A PAN-SARBECOVIRUS VACCINE AT THE END OF YEAR 2, AND A PAN-BETACORONAVIRUS VACCINE AT THE END OF YEAR 5.

NEW TECHOLOGY FOR NEW-OUT DESIGN OF NOVEL ENZYME CATALYSTS

COLLABORATING TO HEAL ADDICTION AND MENTAL HEALTH IN PRIMARY CARE (CHAMP)

R/V THOMAS G, THOMPSON SHIP OPERATIONS NSF 2023-2028 -THIS PROPOSAL IS SUBMITTED TO REQUEST FUNDING FOR THE RESEARCH VESSEL THOMAS G. THOMPSON, OPERATED BY THE UNIVERSITY OF WASHINGTON (UW) AND OWNED BY THE OFFICE OF NAVAL RESEARCH. THE PROPOSAL REQUESTS FUNDS TO CONDUCT OCEANOGRAPHIC RESEARCH MISSIONS SUPPORTED BY THE NATIONAL SCIENCE FOUNDATION IN CALENDAR YEAR 2025 THROUGH 2028. THE INTELLECTUAL AND TECHNICAL MERITS OF THE SCIENCE PROPOSALS HAVE BEEN COMPETITIVELY REVIEWED BY PANELS TO AWARD THE FUNDING FOR THE SCIENTIFIC RESEARCH. IN ADDITION, EACH OF THE NSF-FUNDED SEAGOING SCIENCE PROPOSALS HAD AN ASSOCIATED SHIPTIME AND MARINE EQUIPMENT (SME) REQUEST ASSOCIATED WITH THE PROJECT. THEREFORE, IF THE SCIENCE PROPOSAL - WHICH REQUIRED DATA COLLECTION AT SEA - WAS FOUND TO HAVE TECHNICAL AND INTELLECTUAL MERIT, THEN THE ASSOCIATED SHIPTIME TO COLLECT THE DATA HAS EQUAL MERIT. THE UW SCHOOL OF OCEANOGRAPHY ? MARINE OPERATIONS TAKES GREAT PRIDE IN PROVIDING ESSENTIAL MARINE SCIENCE RESEARCH AND EDUCATIONAL FACILITIES TO NSF-FUNDED INVESTIGATORS AND ACADEMIC FACULTY. THE UW REMAINS COMMITTED TO MANAGING THESE FACILITIES IN A SAFE, COST-EFFECTIVE, AND ENVIRONMENTALLY RESPONSIBLE MANNER. THE OCEANOGRAPHIC RESEARCH VESSELS OF THE ACADEMIC RESEARCH FLEET (ARF), OPERATED BY THE ACADEMIC INSTITUTIONS WITHIN THE UNIVERSITY-NATIONAL OCEANOGRAPHIC LABORATORY SYSTEM (UNOLS) FRAMEWORK, FUNDED BY NSF AND OTHER AGENCIES, HAVE BEEN THE TRADITIONAL MULTI-USE FACILITIES REQUIRED TO EXPAND HUMAN KNOWLEDGE OF THE OCEAN ENVIRONMENT. THESE SHIPS WORKING FROM THE OCEAN SURFACE ARE COMPLEMENTED BY HUMAN-OCCUPIED, REMOTELY OPERATED, AND AUTONOMOUS UNDERSEA VEHICLES (HOV, ROV, AUV) AND SENSORS PROVIDE VITAL TOOLS IN OUR UNDERSTANDING OF THE ROLE OF THE OCEANS IN DETERMINING OUR CLIMATE AND STUDYING AND ACCESSING THE LIVING AND NON-LIVING RESOURCES OF THE WORLD?S SEAS AND SEABEDS. PROPER STEWARDSHIP OF OCEAN RESOURCES AND THEIR WISE USE, AND DATA-DRIVEN DECISION MAKING FOR FUTURE OCEAN- AND COASTAL-RELATED ISSUES ARE NOT POSSIBLE WITHOUT AN INTERESTED AND ENGAGED SCIENTIFIC COMMUNITY AND WELL-INFORMED PUBLIC. SO, PERIODICALLY, UW HOLDS OPEN HOUSES AND OUTREACH EVENTS TO PROVIDE A LEARNING EXPERIENCE FOR LOCAL STUDENTS AND THE PUBLIC INCLUDING TOURS THROUGH THE SHIP FACILITIES AND HANDS-ON DEMONSTRATIONS OF MARINE SCIENCE RESEARCH GUIDED BY FACULTY, STUDENTS AND SHIP CREW MEMBERS. IN 2018, THE UW SCHOOL OF OCEANOGRAPHY TEAMED WITH SCIENTISTS FROM EVERETT COMMUNITY COLLEGE TO TAKE STUDENTS OUT FOR ORCA CRUISE ON EARTH DAY ON THE RACHEL CARSON. ANNUALLY, AROUND 200 PEOPLE TOUR R/V RACHEL CARSON EACH MAY AS PART OF THE UW AQUATIC SCIENCES OPEN HOUSE. IN ADDITION TO TECHNOLOGY, OUR NATIONAL OCEAN ENDEAVOR REQUIRES A DIVERSE CADRE OF TRAINED RESEARCHERS POSSESSING SOUND SCIENCE, MATHEMATICS, AND TECHNICAL EDUCATION: A CRITICAL MASS OF INDIVIDUALS ARE REQUIRED WHO WILL COLLECT AND ANALYZE DATA, AS WELL AS DESIGN THE TOOLS, MODELS AND APPLICATIONS. THESE SEAGOING RESEARCH AND EDUCATIONAL FACILITIES ENABLE SCIENTISTS AND STUDENTS FROM UW AND OTHER INSTITUTIONS NATIONWIDE TO STUDY NATURAL PHENOMENA AND TO INSTRUCT THE FUTURE SCIENTISTS AND STEWARDS OF OUR MARINE ECOSYSTEMS WHILE ON BOARD STATE-OF-THE-ART OCEANOGRAPHIC RESEARCH VESSELS UTILIZING HIGH-QUALITY INSTRUMENTATION. ESSENTIAL TO OUR MISSION IS PROVIDING POST-SECONDARY EDUCATIONAL OPPORTUNITIES FOR STUDENTS OF THE MARINE SCIENCES BY INTRODUCING THEM TO SEAGOING RESEARCH, COLLECTING DATA FOR STUDENT DEVELOPED RESEARCH PROJECTS, AND HAVING THEM PARTICIPATE IN OTHER FUNDED RESEARCH; THESE INCLUDE PROGRAMS LIKE UW UNDERGRADUATE COURSES (OCN 443), MATE INTERNSHIPS, AND THE VISIONS OUTREACH COMPONENT OF THE OCEAN OBSERVATORIES INITIATIVE (OOI-RCA). IN ADDITION, EDUCATION OF K THROUGH 12TH GRADE STUDENTS NATIONWIDE - THROUGH OUTREACH PROGRAMS SUCH AS REVEL, NOAA?S ?TEACHER AT SEA?, AND THE NSF-FUNDED GEOSCIENCES - EARTH, OCEAN, POLAR AND ATMOSPHERIC SCIENCES (GEOPATHS) ARE SUPPORTED ON THE VESSELS OF THE ACADEMIC RESEARCH FLEET. FINALLY, THERE ARE ADDITIONAL OUTREACH PROGRAMS, SUCH AS THE NSF-FUNDED STEMSEAS, UW GEODUC, AND THE ONR-SUPPORTED DINO-SIP PROGRAM WHICH SPECIFICALLY USE THE UW RESEARCH SHIPS TO PROVIDE EDUCATIONAL OPPORTUNITIES FOR NON-TRADITIONAL STEM STUDENTS; THESE PROGRAMS ARE DISCUSSED FURTHER IN THE BROADENING PARTICIPATION SECTION OF THE SUPPLEMENTAL DOCUMENTATION. THE UNIVERSITY OF WASHINGTON, WITH THE SUPPORT OF THE NATIONAL SCIENCE FOUNDATION AND WITH COORDINATION BY THE UNIVERSITY-NATIONAL OCEANOGRAPHIC LABORATORY SYSTEM, REMAINS DEDICATED TO, AND FOCUSED ON, FURTHERING OUR UNDERSTANDING OF THE WORLD OCEAN, THE LIVING AND NON-LIVING RESOURCES THEREIN, AND THEIR INTERACTIONS WITH THE APPROXIMATELY FIFTY PERCENT OF OUR CITIZENS WHO LIVE WITHIN FIFTY MILES OF THE SHORELINE. 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 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 NOT PLANNED FOR THIS AWARD.

WASHINGTON SEA GRANT PROGRAM PLAN FOR RENEWAL OF SEA GRANT COLLEGE SUPPORT 2018 - 2022

DISCOVER CENTER: CARDIOVASCULAR DISEASE AND TRAFFIC-RELATED AIR POLLUTION

UNIVERSITY OF WASHINGTON CENTER FOR NUCLEAR ORGANIZATION AND FUNCTION

RESPIRATORY RESEARCH TRAINING GRANT

HEALTH PROMOTION AND DISEASE PREVENTION RESEARCH CENTER

AIDS EDUCATION AND TRAINING CENTERS PROGRAM

GH15-1549, MALAWI: HUMAN RESOURCES FOR HEALTH (HRH) CAPACITY BUILDING IN MALAWI UNDER THE PRESIDENT'S EMERGENCY PLAN FOR AIDS RELIEF (PEPFAR)

THE PURPOSE OF THIS AGREEMENT IS TO FUND RESEARCH SUPPORTING THE DEFENSE ADVANCED RESEARCH PROJECTS AGENCY (DARPA) BIOLOGICAL TECHNOLOGIES OFFICES (BTO) HARNESSING ENZYMATIC ACTIVITY FOR BACTERIAL TOXINS (HEALR) PROGRAM.

UNIVERSITY OF WASHINGTON CENTER OF EXCELLENCE IN OPIOID ADDICTION RESEARCH

NATIONAL NETWORK OF SEXUALLY TRANSMITTED DISEASES CLINICAL PREVENTION TRAINING CENTERS (NNPTC). UNIVERSITY OF WASHINGTON STD PREVENTION TRAINING CENTER.

UNIVERSITY OF WASHINGTON ARBOVIRAL RESEARCH NETWORK (UWARN)

BUILDING SUSTAINABLE LABORATORY QUALITY SYSTEMS IN COTE ??D IVOIRE UNDER THE PRESIDENT??S EMERGENCY PLA

NUCLEAR THEORY

VACCINES FOR FENTANYL AND ITS DERIVATIVES: A STRATEGY TO REDUCE ILLICIT USE AND OVERDOSE - ABSTRACT. THIS UG3/UH3 PROJECT WILL DEVELOP VACCINES AGAINST FENTANYL AND FENTANYL-LIKE COMPOUNDS AS A STRATEGY TO REDUCE ILLICIT OPIOID USE AND THE INCIDENCE OF FATAL OVERDOSES. PROPOSED ACTIVITIES WILL INCLUDE LEAD VACCINE SELECTION AND OPTIMIZATION, MANUFACTURING OF GMP VACCINES, AND IND-ENABLING GLP TOXICOLOGY STUDIES. THE US HAS SEEN DRAMATIC INCREASES IN FATAL OVERDOSES DUE TO HEROIN, COUNTERFEIT PRESCRIPTION DRUGS, AND COCAINE ADULTERATED WITH FENTANYL OR FENTANYL-LIKE ANALOGS. CURRENT MEDICATIONS MAY NOT BE SUFFICIENT TO ADDRESS THE OPIOID OVERDOSE EPIDEMIC. AS A COMPLEMENTARY STRATEGY TO CURRENT MEDICATIONS, WE WILL DEVELOP VACCINES AGAINST FENTANYL AND FENTANYL-LIKE COMPOUNDS TO REDUCE THEIR ABUSE LIABILITY AND LETHALITY. OUR TEAM HAS ALREADY DEVELOPED VACCINES AGAINST HEROIN AND OXYCODONE THAT INDUCE ANTIBODIES EFFECTIVE IN REDUCING OPIOID DISTRIBUTION TO THE BRAIN, OPIOID-INDUCED BEHAVIORS, AND OPIOID-INDUCED RESPIRATORY DEPRESSION. VACCINES EFFECTIVELY AND SELECTIVELY TARGET THE INTENDED OPIOID BUT DO NOT INTERFERE WITH ENDOGENOUS OPIOIDS NOR WITH APPROVED PHARMACOTHERAPIES. OPIOID VACCINES OFFER A LONG-LASTING, SAFE AND COST-EFFECTIVE INTERVENTION COMPLEMENTARY TO MEDICATION ASSISTED TREATMENT (MAT). VACCINES MAY REDUCE OVERDOSES IN OPIOID USERS AS WELL AS PROTECT THOSE IN PROFESSIONS (E.G., LAW ENFORCEMENT, AIRPORT SECURITY, POSTAL WORKERS) AT RISK OF ACCIDENTAL EXPOSURE TO FENTANYL AND FENTANYL ANALOGS. OUR TEAM HAS IDENTIFIED A CANDIDATE FENTANYL VACCINE CONSISTING OF A FENTANYL-BASED HAPTEN (F0) CONJUGATED TO THE KEYHOLE LIMPET HEMOCYANIN (KLH) CARRIER PROTEIN, AND ADSORBED ONTO ALUM ADJUVANT. IMMUNIZATION WITH F0-KLH REDUCES FENTANYL DISTRIBUTION TO THE BRAIN, AND SELECTIVELY REDUCES FENTANYL-INDUCED ANTINOCICEPTION AND RESPIRATORY DEPRESSION IN RATS. WE WILL FURTHER OPTIMIZE THE LEAD F0-KLH BY TESTING ALTERNATIVE CARRIER PROTEINS. IN PARALLEL WE WILL DEVELOP OTHER CONJUGATE VACCINES CONTAINING A NEW SERIES OF HAPTENS (FN) TO TARGET CARFENTANIL, REMIFENTANIL, AND OTHER FENTANYL ANALOGS. DEVELOPMENT WILL BE STAGGERED ACROSS UG3/UH3 PHASES, AND WE EXPECT THAT THE FIRST LEAD F0-CARRIER CONJUGATE VACCINE WILL BE READY FOR IND FILING BY THE END OF YEAR 3. AIM1 FOCUSES ON OPTIMIZATION OF VACCINES CONTAINING THE LEAD F0 AND NEW FN HAPTENS CONJUGATED TO INDUSTRY-STANDARD CARRIER PROTEINS, INCLUDING TWO E. COLI-EXPRESSED CARRIERS OBTAINED FROM OUR INDUSTRY PARTNER FINABIOSOLUTIONS. LEADS ARE IDENTIFIED FOR EFFICACY IN INDUCING ANTIBODIES THAT WILL REDUCE FENTANYL (OR FENTANYL ANALOG) DISTRIBUTION TO THE BRAIN AS WELL AS REDUCING ANTINOCICEPTION, RESPIRATORY DEPRESSION AND LETHALITY IN RATS. AIM1 ALSO CHARACTERIZES ADDITIONAL IMMUNIZATION REGIMENS AND VACCINE EFFICACY IN FENTANYL SELF-ADMINISTRATION RAT MODELS. AS A CONTINGENCY PLAN, AIM2 TESTS WHETHER AIM1 LEADS CONTAINING F0 AND FN HAPTENS CAN BE CO-ADMINISTERED IN A MULTICOMPONENT VACCINE FORMULATION TO SIMULTANEOUSLY TARGET FENTANYL AND ITS ANALOGS. AIM3 FOCUSES ON MANUFACTURING OF GMP VACCINES AND EVALUATE THEIR SAFETY IN GLP PRE-CLINICAL TOXICOLOGY STUDIES THROUGH CMO AND CRO PARTNERS. AIM3 WILL THEN FILE AN IND FOR AT LEAST ONE VACCINE FORMULATION AGAINST FENTANYL AND/OR ITS ANALOGS.

INSTITUTE OF TRANSLATIONAL HEALTH SCIENCES

NORTHWEST GENOMICS CENTER

CLINICAL TRIALS NETWORK: PACIFIC NORTHWEST NODE

SURGICAL CARE AND OUTCOMES ASSESSMENT PROGRAM COMPARATIVE EFFECTIVENESS RESEARCH

HOST DEFENSE TRAINING IN ALLERGY AND INFECTIOUS DISEASES

MECHANISMS AND MARKERS OF PROSTATE CANCER METASTASES

NATURAL HAZARDS ENGINEERING RESEARCH INFRASTRUCTURE: NATURAL HAZARD AND DISASTER RECONNAISSANCE (RAPID) FACILITY 2021-2025

RESEARCH INFRASTRUCTURE: MID-SCALE RI-1 (M1:IP): CREATING AN OFFSHORE SUBDUCTION ZONE OBSERVATORY IN CASCADIA WITH THE OCEAN OBSERVATORIES INITIATIVE REGIONAL CABLED ARRAY -EARTH?S GREATEST GEOLOGICAL HAZARDS ARE CONCENTRATED IN ITS SUBDUCTION ZONES, THE PLACES WHERE TWO TECTONIC PLATES CONVERGE AND COLLIDE. ALL KNOWN EARTHQUAKES WITH MAGNITUDES ?8.8 HAVE TAKEN PLACE AT SUBDUCTION ZONES, AS HAVE THE MOST DEVASTATING TSUNAMIS. THE CASCADIA SUBDUCTION ZONE, SPANNING THE OFFSHORE COASTS FROM NORTHERN CALIFORNIA TO BRITISH COLUMBIA, HOSTS EARTHQUAKES UP TO MAGNITUDE 9 EVERY FEW HUNDRED YEARS, THE LAST OF WHICH WAS IN 1700. WHILE THERE ARE DENSE SEISMIC AND GEODETIC SENSOR NETWORKS TODAY ON LAND IN THE PACIFIC NORTHWEST, THE OFFSHORE REGION, WHERE ALMOST ALL THE LOCKED PLATE BOUNDARY AND EXPECTED EARTHQUAKE SLIP WILL OCCUR, IS LARGELY DEVOID OF SUCH INSTRUMENTS IN US WATERS. THIS PROJECT WILL TAKE ADVANTAGE OF THE EXISTING NSF-FUNDED REGIONAL CABLED OBSERVATORY THAT BRINGS POWER AND THE INTERNET INTO THE OCEANS ON THE MARGIN OFFSHORE NEWPORT, OREGON. INSTRUMENTS, INCLUDING SEISMIC SENSORS AND SEAFLOOR PRESSURE GAUGES, WILL BE ADDED TO THE CABLED INFRASTRUCTURE. REAL-TIME DATA STREAMING FROM THE RESULTING SUBDUCTION ZONE OBSERVATORY WILL HELP ANSWER FUNDAMENTAL QUESTIONS ABOUT HOW SUBDUCTION ZONE FAULTS WORK AND CAN BE USED TO ENHANCE EXISTING SYSTEMS FOR EARTHQUAKE AND TSUNAMI WARNING. A FUNDAMENTAL ?GRAND CHALLENGE? IN THE GEOSCIENCES TODAY IS TO IMPROVE UNDERSTANDING OF HOW SUBDUCTION ZONE PLATE INTERFACE FAULTS WORK. THIS REQUIRES SUSTAINED OFFSHORE OBSERVATIONS IN MULTIPLE SUBDUCTION ZONES WITH CONTRASTING PROPERTIES TO CHARACTERIZE HOW DEFORMATION IS PARTITIONED AMONG LARGE EARTHQUAKES, SLOW SLIP, AND ASEISMIC CREEP. THE CASCADIA SUBDUCTION ZONE IS A GLOBAL ENDMEMBER, OWING TO THE YOUNG AGE OF THE SUBDUCTING PLATE AND THICK SEDIMENT COVER. THE OCEAN OBSERVATORIES INITIATIVE REGIONAL CABLED ARRAY INCLUDES A SOUTHERN CABLE LOCATED ON THE SLOPE AND SHELF OF THE CASCADIA SUBDUCTION ZONE OFF NEWPORT, OREGON. THIS ARRAY HAS GREAT POTENTIAL FOR SUBDUCTION ZONE STUDIES BECAUSE IT IS IN AN IDEAL CENTRAL LOCATION IN CASCADIA WHERE THE GRADIENT IN MEGATHRUST COUPLING EXTENDS WELL OFFSHORE AND THERE ARE ONGOING CLUSTERS OF SEISMICITY AND LOW FREQUENCY EARTHQUAKES BENEATH THE SHELF. THIS PROJECT WILL ADD CABLED SEAFLOOR SCIENCE JUNCTION BOXES TO EACH OF THREE PRIMARY NODES ON THE CONTINENTAL SLOPE AND SHELF, NONE OF WHICH ARE PRESENTLY INSTRUMENTED FOR GEOPHYSICS. EACH JUNCTION BOX WILL HOST A SUITE OF GEOPHYSICAL SENSORS, COMPRISING A BURIED BROADBAND SEISMOMETER, A LOW-FREQUENCY HYDROPHONE, STRONG MOTION ACCELEROMETERS, CALIBRATED PRESSURE GAUGES AND A CURRENT METER, WITH ROOM FOR FUTURE EXPANSION. IN CONJUNCTION WITH NODES THAT ALREADY HAVE GEOPHYSICAL SENSORS, THIS WILL CREATE A WORLD CLASS OFFSHORE GEOPHYSICAL OBSERVATORY TO STUDY FAULT COUPLING AND DEFORMATION OF THE CASCADIA MEGATHRUST AND THE OVERLYING ACCRETIONARY PRISM ACROSS A ~100 KM SECTION OFFSHORE. THE OBSERVATORY CAN ADDRESS THE FOLLOWING QUESTIONS: (1) HOW DOES THE LOCKING OF THE CASCADIA MEGATHRUST TRANSITION BETWEEN THE DEFORMATION FRONT AND THE COASTLINE OFF CENTRAL OREGON? (2) IS THERE TRANSIENT SLIP BEHAVIOR ? SLOW SLIP, TREMOR, AND/OR VERY LOW FREQUENCY EARTHQUAKES ? OFFSHORE SPANNING THE LOCKED ZONE AND ITS DOWNDIP TRANSITION? (3) HOW ARE THE CLUSTERS OF SHALLOW EARTHQUAKES OFFSHORE LINKED TO THE MEGATHRUST? (4) WHAT IS THE BASELINE DEFORMATION RATE AND FAULT SLIP BEHAVIOR OF THE ACCRETIONARY PRISM? BECAUSE THE SUBMARINE CABLE STREAMS DATA TO SHORE AT THE SPEED OF LIGHT, THIS OBSERVATORY CAN PROVIDE THE NATION?S FIRST OFFSHORE REAL-TIME EARTHQUAKE AND TSUNAMI EARLY WARNING DETECTOR, ADDING TO AND COMPLEMENTING THE USGS?S SHAKEALERT EARTHQUAKE WARNING SYSTEM AND NOAA?S TSUNAMI BUOYS. IT CAN ALSO SUPPORT RESEARCH INTO NEW WARNING TECHNOLOGIES. BOTH UNDERGRADUATE SUMMER INTERNS AND GRADUATE STUDENTS WILL BE TRAINED ON CABLED GEOPHYSICAL OBSERVATORIES, INCLUDING AT-SEA EXPERIENTIAL LEARNING PROGRAMS PRIOR TO AND DURING INSTALLATION OF THE OBSERVATORY. A WORKSHOP WILL INTRODUCE EARLY CAREER RESEARCHERS TO THE SCIENTIFIC GOALS AND INFRASTRUCTURE, PROVIDE HANDS-ON EXPERIENCE WITH THE TOOLS FOR ACCESSING AND VISUALIZING THE DATA STREAMS, AND EXPLORE IDEAS FOR FUTURE ANALYSIS. BECAUSE THE SUBMARINE CABLE STREAMS DATA TO SHORE AT THE SPEED OF LIGHT, THIS OBSERVATORY CAN PROVIDE THE NATION?S FIRST OFFSHORE REAL-TIME EARTHQUAKE AND TSUNAMI EARLY WARNING DETECTOR, ADDING TO AND COMPLEMENTING THE USGS?S SHAKEALERT EARTHQUAKE WARNING SYSTEM AND NOAA?S TSUNAMI BUOYS. IT CAN ALSO SUPPORT RESEARCH INTO NEW WARNING TECHNOLOGIES. BOTH UNDERGRADUATE SUMMER INTERNS AND GRADUATE STUDENTS WILL BE TRAINED ON CABLED GEOPHYSICAL OBSERVATORIES, INCLUDING AT-SEA EXPERIENTIAL LEARNING PROGRAMS PRIOR TO AND DURING INSTALLATION OF THE OBSERVATORY. A WORKSHOP WILL INTRODUCE EARLY CAREER RESEARCHERS TO THE SCIENTIFIC GOALS AND INFRASTRUCTURE, PROVIDE HANDS-ON EXPERIENCE WITH THE TOOLS FOR ACCESSING AND VISUALIZING THE DATA STREAMS, AND EXPLORE IDEAS FOR FUTURE ANALYSIS. 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.

BIOSTATISTICS, EPIDEMIOLOGIC & BIOINFORMATIC TRAINING IN ENVIRONMENTAL HEALTH

CLINICAL SEQUENCING IN CANCER: CLINICAL ETHICAL AND TECHNOLOGICAL STUDIES

THE SUPPORT AND IMPROVEMENT OF SHAKEALERT 2021-2023: COLLABORATIVE RESEARCH WITH UNIV. OF CALIFORNIA AT BERKELEY, CALIFORNIA INSTITUTE OF TECHNOLOGY, UNIV. OF WASHINGTON, AND UNIV. OF OREGON, DATED 4/23/2021, REVISED 6/29/2021

GH11-1152, REDUCING NEW HIV INFEC IN BONJANALA PLATINUM , N.W. PROV OF S. AFRICA

UNIVERSITY OF WASHINGTON (UW) SEXUALLY TRANSMITTED INFECTIONS (STI) COOPERATIVE RESEARCH CENTER (CRC) - SYPHILIS VACCINE TO PROTECT AGAINST LOCAL AND DISSEMINATED T. PALLIDUM INFECTION

UW 4-DIMENSIONAL GENOMIC ORGANIZATION OF MAMMALIAN EMBRYOGENESIS CENTER

PRETERM EPO NEUROPROTECTION TRIAL (PENUT TRIAL) CCC

WSG OMNIBUS ABSTRACT PURPOSE THE GOAL OF WSGS FEDERALLY FUNDED ACTIVITIES IS TO HELP PEOPLE AND MARINE LIFE THRIVE BY SUPPLYING RESEARCH, TECHNICAL EXPERTISE AND EDUCATIONAL ACTIVITIES THAT SUPPORT THE RESPONSIBLE USE AND CONSERVATION OF WASHINGTONS OCEAN AND COASTAL ECOSYSTEMS. ACTIVITIES TO BE PERFORMED OUTREACH - WSG OUTREACH ACTIVITIES INCLUDE: ENGAGEMENT ACTIVITIES CONNECT WASHINGTONIANS TO RESEARCH, INFORMATION, AND PRACTICAL TOOLS FOR SUSTAINABLY USING, MANAGING, AND ENJOYING OCEAN AND COASTAL RESOURCES. TECHNICAL ASSISTANCE IS PROVIDED IN A BROAD RANGE OF TOPIC AREAS, INCLUDING AQUACULTURE, FISHERIES, WATER QUALITY, HABITAT RESTORATION, CITIZEN SCIENCE, INVASIVE SPECIES, COASTAL DEVELOPMENT AND MANAGEMENT, MARINE OPERATIONAL SAFETY, OIL SPILL PREVENTION AND HAZARD RESILIENCE. WSG COMMUNICATIONS KEEP THE PUBLIC UP TO DATE ON CURRENT RESEARCH AND SUPPORT MARINE USER NEEDS FOR THE LATEST NEWS ON RELEVANT ISSUES VIA THE WSG WEBSITE, SOCIAL MEDIA, COASTAL CAF RADIO PROGRAM, AND OTHER PUBLICATIONS AND MATERIALS SUPPORTING THE RANGE OF WSG ACTIVITIES. EDUCATION ACTIVITIES ENHANCE THE PUBLICS UNDERSTANDING AND STEWARDSHIP OF MARINE RESOURCES, SUPPORT EDUCATIONAL PROGRAMS FOR K-12 STUDENTS, INCLUDING AN ANNUAL SCIENCE CAMP AND A STATEWIDE OCEAN SCIENCES TOURNAMENT FOR HIGH SCHOOL STUDENTS. FELLOWSHIPS - WSG ALSO PRESENTS UNDERGRADUATE, GRADUATE AND POSTDOCTORAL STUDENTS WITH OPPORTUNITIES TO COMPETE FOR FELLOWSHIP PROGRAMS THAT EXPAND HORIZONS, ENHANCE FUTURE CAREERS AND SEEK TO BUILD PATHWAYS INTO MARINE SCIENCE AND POLICY CAREERS FOR INDIVIDUALS WHO ARE HISTORICALLY UNDERREPRESENTED IN THOSE FIELDS. RESEARCH - WSG FUNDED RESEARCH HELPS PEOPLE BETTER UNDERSTAND AND ADDRESS THE CHALLENGES FACING OUR OCEAN AND COASTS. WSG WILL SPONSOR RESEARCH PROJECTS THAT COMBINE SCIENTIFIC EXCELLENCE WITH A FOCUS ON SOLVING PROBLEMS FACED BY OCEAN USERS AND MANAGERS. EXPECTED OUTCOMES EXPECTED OUTCOMES ARE FULLY DESCRIBED IN THE WSG STRATEGIC PLAN IN THE CONTEXT OF FOUR FOCUS AREAS: ENVIRONMENTAL LITERACY AND WORKFORCE DEVELOPMENT: ENVIRONMENTAL EDUCATION IS ESSENTIAL TO BUILD SCIENTIFIC LITERACY AND APPRECIATION FOR MARINE RESOURCES AND ECOSYSTEMS. WAS OCEAN ECONOMY RELIES ON A WELL-TRAINED WORKFORCE CAPABLE OF DEALING WITH THE COMPLEXITY OF ITS MARINE SECTOR. RESILIENT COMMUNITIES AND ECONOMIES: RAPID COASTAL GROWTH HAS ADDED STRESS TO LOCAL COASTAL ECOSYSTEMS. STAKEHOLDERS NEED ACCURATE INFORMATION TO MAKE SCIENCE-BASED DECISIONS, PRESERVE COASTAL ECOSYSTEM SERVICES, AND IDENTIFY LOW-IMPACT DEVELOPMENT APPROACHES. HEALTHY COASTAL ECOSYSTEMS: WASHINGTON FACES MANY OBSTACLES TO MAINTAINING AND RESTORING HEALTHY COASTAL ECOSYSTEMS INCLUDING HEAVY INDUSTRY, HYDROELECTRIC DAMS, OVERHARVEST, DEGRADED WATER QUALITY, OCEAN ACIDIFICATION, AND INVASIVE SPECIES. THERE IS GROWING RECOGNITION OF THE NEED FOR ECOSYSTEM BASED MANAGEMENT THAT INTEGRATES ECOLOGICAL, SOCIAL, ECONOMIC AND INSTITUTIONAL PERSPECTIVES. SUSTAINABLE FISHERIES AND AQUACULTURE: SEAFOOD HARVESTING IS A VITAL PART OF CULTURE AND COMMERCE AND THE LIVES OF WASHINGTONS PEOPLE ARE INTERTWINED WITH ITS LIVING MARINE RESOURCES. FOR MANY INDIGENOUS PEOPLE THE CONNECTIONS TO SEAFOOD RUN EVEN DEEPER WITH TIES TO CULTURAL PRACTICES AND TRADITIONS THAT HAVE PERSISTED SINCE TIME IMMEMORIAL. IT IS ESSENTIAL THAT FISHERIES AND AQUACULTURE CONTINUE TO SUPPLY WHOLESOME SEAFOOD, JOBS AND ECONOMIC AND CULTURAL BENEFITS. INTENDED BENEFICIARIES THE INTENDED BENEFICIARIES OF SUPPORTED ACTIVITIES INCLUDE INTERNATIONAL, FEDERAL, TRIBAL, STATE AND LOCAL GOVERNMENTS; LOCAL COMMUNITIES; BUSINESSES; PEOPLE FROM ACADEMIA; K-12 STUDENTS; NONGOVERNMENTAL ORGANIZATIONS; AND ULTIMATELY, ALL PEOPLE WHO LIVE AND WORK IN WASHINGTON STATE. SUBRECIPIENT ACTIVITIES FEDERALLY FUNDED RESEARCH PROJECTS WILL BE LED BY UNIVERSITY OF WASHINGTON (UW) AND NON-UW SUBRECIPIENTS WHO WILL CONDUCT A MIX OF BASIC AND APPLIED RESEARCH AND EACH PROJECT WILL INCLUDE AN ENGAGEMENT PLAN ENSURING THE RESULTS OF

RESEARCH TRAINING IN HEMATOLOGY

CENTER FOR REPRODUCIBLE SYSTEMS FOR BIOMEDICAL MODELING

SEQUENCE AND ASSEMBLY OF SEGMENTAL DUPLICATIONS

INQUBATOR FOR QUANTUM SIMULATIONS OF QUANTUM SYSTEMS ( IQUS2 )

COSMIC: COMMONSENSE MACHINE INTELLIGENCE MACHINE COMMON SENSE (MCS)

COMPREHENSIVE BIOLOGY: EXPLOITING THE YEAST GENOME

SCALING UP VOLUNTARY MALE CIRCUMCISION TO PREVENT HIV TRANSMISSION IN ZIMBABWE

THE GENERATION 2 AXION DARK-MATTER EXPERIMENT

PHARMACOGENETICS IN RURAL AND UNDERSERVED POPULATIONS

THE GOAL OF NESSP WILL BE TO INSPIRE, EDUCATE AND RECRUIT THE NEXT GENERATION OF STEM STUDENTS THROUGH STANDARDS-BASED, MATHINFUSED NASA MATERIALS AN

BACK PAIN OUTCOMES USING LONGITUDINAL DATA (BOLD)

HIV TREATMENT FOR RESEARCH SUBJECTS OR BY RESEARCHERS IN KENYA

UW PRACTICE-BASED SUICIDE PREVENTION RESEARCH CENTER - IN HIS PROCLAMATION FOR NATIONAL MENTAL HEALTH AWARENESS MONTH 2021, PRESIDENT BIDEN EMPHASIZED “MY ADMINISTRATION IS COMMITTED TO ADVANCING SUICIDE PREVENTION BEST PRACTICES AND IMPROVING NON-PUNITIVE CRISIS RESPONSE.” THE UNIVERSITY OF WASHINGTON PRACTICE-BASED SUICIDE PREVENTION RESEARCH CENTER DIRECTLY ANSWERS THE PRESIDENT'S CALL TO ACTION IN OUTPATIENT MEDICAL SETTINGS THROUGH ENHANCING THERAPEUTIC ALLIANCE AND INCREASED SELF-EFFICACY OF ADOLESCENT AND YOUNG ADULT PATIENTS, THEIR PROVIDERS, AND THEIR FAMILIES TO MANAGE SUICIDE RISK. THE CENTER'S APPROACH TO IMPROVING OUTCOMES ACROSS THE SUICIDE CARE PATHWAY FROM IDENTIFICATION OF SUICIDE RISK THROUGH ASSESSMENT TO DECISION MAKING AND RISK MANAGEMENT, CRISIS RESPONSE, TREATMENT OF SUICIDALITY, AND LONG-TERM SURVEILLANCE AND FOLLOW-UP IS CONSISTENT WITH THE RECOMMENDATIONS OF THE JOINT COMMISSION, ZERO SUICIDE, NATIONAL ACTION ALLIANCE FOR SUICIDE PREVENTION, AND THE SURGEON GENERAL. THE CENTER, LED BY CLINICAL RESEARCHERS WHO TREAT SUICIDAL PATIENTS IN PARTNERSHIP WITH INFORMATICS RESEARCHERS AND OPERATIONAL EXPERTS, TAKES A STAKEHOLDER-BASED CO-DESIGN APPROACH INTEGRATING HUMAN CENTERED DESIGN (HCD) AND MULTI-PHASIC OPTIMIZATION (MOST) TO DEVELOP INTERVENTIONS FOR THE OUTPATIENT MEDICAL SETTING. THE CENTER REPRESENTS A UNIQUE PARTNERSHIP BETWEEN THE SCHOOL OF MEDICINE'S DEPARTMENTS OF PSYCHIATRY AND BEHAVIORAL SCIENCES, PEDIATRICS AND FAMILY MEDICINE WITH BIOINFORMATICS AND MEDICAL EDUCATION. THE CENTER ALSO BRIDGES UW'S MANY RESOURCES: THE CENTER FOR SUICIDE PREVENTION AND RECOVERY, THE INSTITUTE FOR TRANSLATIONAL HEALTH SCIENCES (THE UW CTSA) AND ITS RESEARCH INFORMATION TECHNOLOGY TEAM, AND THE AIMS CENTER (UW IMPLEMENTATION AND TRAINING CENTER FOR COLLABORATIVE CARE). THE ADMINISTRATIVE CORE WILL SERVE AS THE COMMUNICATION HUB BETWEEN CENTER CORES, OUR EXPERT AND THREE STAKEHOLDER ADVISORY BOARDS, THE R03 PILOT GRANT PROGRAM THROUGH WHICH OUR COLLABORATING SCHOLARS FROM OTHER DISCIPLINES WHO ARE NEW TO SUICIDE PREVENTION WILL RECEIVE MENTORING, TRAINING, AND EXPERIENCE. THE SIGNATURE PROJECT (R01) WILL COLLABORATE WITH PEDIATRIC MEDICAL SETTINGS TO OPTIMIZE TREATMENT AND MAXIMIZE REFERRALS TO A BRIEF OUTPATIENT CRISIS INTERVENTION AS AN ALTERNATIVE TO EMERGENCY DEPARTMENT REFERRAL. THE AMPERE R34 PROJECT WILL USE THE PRINCIPLES OF HCD TO CREATE A CLINICALLY ACTIONABLE PATHWAY FOR ECOLOGICAL MOMENTARY ASSESSMENT OF SUICIDE RISK THAT IS ACCEPTABLE AND USABLE FOR BOTH YOUNG ADULT PATIENTS AND THEIR PRIMARY CARE PROVIDERS. THE ISSP R34 PROJECT WILL ADAPT EXISTING TECHNOLOGY TO USE SAFETY PLAN DATA TO PROVIDE CLINICAL DECISION SUPPORT TO HEALTHCARE PROVIDERS IN PEDIATRIC MEDICAL SETTINGS. THE AM-COCM R34 PROJECT WILL ADAPT THE AESCHI MODEL – CORE PRINCIPLES OF CARE ADVOCATED BY SUICIDE EXPERTS – FOR COLLABORATIVE CARE FOR ADOLESCENTS AND YOUNG ADULTS IN PRIMARY CARE CLINICS. RESEARCH PROJECTS WILL WORK WITH THE METHODS CORE TO CREATE POINT-OF-CARE CLINICAL DECISION SUPPORT AND ELECTRONIC HEALTH RECORD INTEGRATION. THE METHODS CORE WILL PROVIDE RESEARCH INFRASTRUCTURE TO THE RESEARCH PROJECTS, INCLUDING COMMON DATA ELEMENTS AND A DATA REPOSITORY HARMONIZED WITH ELECTRONIC HEALTH RECORDS. THE CENTER WILL CONCLUDE WITH A NATIONAL POLICY BRIEFING ON CENTER FINDINGS TO MAXIMIZE DISSEMINATION.

MASSIVELY PARALLEL CHARACTERIZATION OF VARIANTS AND ELEMENTS IMPACTING TRANSCRIPTIONAL REGULATION IN DYNAMIC CELLULAR SYSTEMS - SUMMARY / ABSTRACT A MAJOR FRACTION OF HERITABILITY FOR COMMON DISEASES, AS WELL AS FOR THE PENETRANCE AND EXPRESSIVITY OF RARE DISEASES, PARTITIONS TO DISTAL REGULATORY ELEMENTS IN THE HUMAN GENOME, OVERWHELMINGLY CELL TYPE-SPECIFIC ENHANCERS. HOWEVER, A RATE-LIMITING CHALLENGE FOR THE FIELD HAS BEEN HOW TO IDENTIFY THE SPECIFIC VARIANTS, ELEMENTS AND REGULATED GENES THAT MEDIATE THESE EFFECTS ON DISEASE LIABILITY. TOWARDS THE OVERALL GOALS OF THE IMPACT OF GENOMIC VARIATION ON FUNCTION (IGVF) CONSORTIUM, WE PROPOSE TO TEST OVER ONE MILLION HUMAN REGULATORY ELEMENTS OR VARIANTS FOR THEIR FUNCTIONAL EFFECTS ON TRANSCRIPTIONAL REGULATION, AS WELL AS TO QUERY OVER 100,000 DISTAL REGULATORY ELEMENTS FOR THE GENE(S) THAT THEY REGULATE. A FIRST THEME OF OUR PROPOSAL IS THE DIVERSITY OF MULTIPLEX TECHNOLOGIES THAT WE WILL EMPLOY TO THESE ENDS, INCLUDING MASSIVELY PARALLEL REPORTER ASSAYS (MPRAS), CRISPRQTL, SATURATION GENOME EDITING, MULTIPLEX PRIME EDITING AND SINGLE CELL COMBINATORIAL INDEXING, MANY OF WHICH WE PIONEERED. A SECOND THEME IS A FOCUS ON DYNAMIC CELLULAR SYSTEMS THAT ENABLE A GIVEN LIBRARY OF VARIANTS AND/OR ELEMENTS TO BE TESTED ACROSS A BROAD RANGE OF CELL TYPES AND STATES WITHIN A SINGLE EXPERIMENT; THESE WILL INCLUDE ESC-DERIVED NEURONAL PROGENITORS, CARDIOMYOCYTES, EMBRYOID BODIES, GASTRULOIDS AND ORGANOIDS, AND IN SELECT CASES, MICE. A THIRD THEME INVOLVES LEVERAGING OUR EXPERIENCE (E.G. CADD, A WIDELY USED, GENOME-WIDE CATALOG OF VARIANT EFFECT PREDICTIONS) TO SUPPORT THE OVERARCHING GOALS OF IGVF. SPECIFICALLY, WE ENVISION USING FUNCTIONAL MEASUREMENTS GENERATED BY US AND OTHERS TO PRODUCE WELL-CALIBRATED PREDICTIONS OF ENHANCER ACTIVITY AND VARIANT EFFECTS THAT ARE CONTINUOUS ALONG THE BRANCHING TRAJECTORIES THAT COMPRISE HUMAN DEVELOPMENT. OUR SPECIFIC AIMS ARE AS FOLLOWS: (1) TO PERFORM MASSIVELY PARALLEL VALIDATION AND FUNCTIONAL CHARACTERIZATION OF CANDIDATE HUMAN ENHANCERS IN A BROAD RANGE OF CELL TYPE CONTEXTS. (2) TO PERFORM MASSIVELY PARALLEL CHARACTERIZATION OF HUMAN GENETIC VARIANTS WITH POTENTIAL ROLES IN HUMAN DISEASE. (3) TO CONTRIBUTE TO A COMPREHENSIVE VARIANT-ELEMENT-PHENOTYPE CATALOG WHILE TAKING A LEADERSHIP ROLE IN SYNERGISTIC INTERACTIONS WITHIN IGVF, IN THE DISSEMINATION OF METHODS, DATA AND PREDICTIONS, AND IN THE OVERARCHING GOALS OF THE CONSORTIUM.

COMPLETE TRIP - ITS4US DEPLOYMENT PROGRAM PHASES 2 & 3

CENTER FOR NATIVE POPULATION HEALTH DISPARITIES

APP FOR AAD 936-3090

INTERDISCIPLINARY LEADERSHIP TRAINING IN NEURODEVELOPMENTAL/RELATED DISABILITIES

THIS COOPERATIVE AGREEMENT SHALL BE PERFORMED IN ACCORDANCE WITH STATEMENT OF WORK, ENTITLED 'HAMMERBLADE: CONTINUOUS SYNTHESIS OF POLYMORPHIC HARDW

HABITABLE PLANETS AND EVOLUTION OF BIOLOGICAL COMPLEXITY

1/4-A GENOMIC APPROACH TO SCHIZOPHRENIA

1/3 GENOMICS OF SCHIZOPHRENIA IN THE SOUTH AFRICAN XHOSA - PROJECT DESCRIPTION THE GOAL OF THIS INTERNATIONAL COLLABORATIVE PROJECT, IN RESPONSE TO PAR-20-027, IS TO CHARACTERIZE THE GENETIC ARCHITECTURE OF SCHIZOPHRENIA IN THE XHOSA POPULATION OF SOUTH AFRICA. THE THREE PARTICIPATING SITES HAVE ALREADY SUCCESSFULLY ESTABLISHED THE INFRASTRUCTURE NECESSARY TO UNDERTAKE THE AIMS OF THIS PROPOSAL. THE THREE SITES ARE UNIVERSITY OF WASHINGTON, SEATTLE (MARY-CLAIRE KING, JACK MCCLELLAN, TOM WALSH, MPIS); COLUMBIA UNIVERSITY, NEW YORK (EZRA SUSSER, PI); AND UNIVERSITY OF CAPE TOWN, SOUTH AFRICA (DAN STEIN, PI). AFRICAN POPULATIONS HARBOR FAR MORE GENETIC VARIATION THAN OUT-OF-AFRICA POPULATIONS, FACILITATING DISCOVERY OF ASSOCIATIONS BETWEEN GENOTYPES AND PHENOTYPES. OUR INITIAL STUDY (GULSUNER AT AL., SCIENCE, 2020) WAS THE FIRST LARGE-SCALE GENETIC STUDY OF SCHIZOPHRENIA IN AN ANCESTRAL AFRICAN POPULATION. WE DISCOVERED THAT XHOSA INDIVIDUALS WITH SCHIZOPHRENIA (CASES) ARE ENRICHED FOR RARE DAMAGING MUTATIONS IN GENES INTOLERANT TO SUCH MUTATIONS. THE EFFECT WAS PARTICULARLY STRONG FOR DAMAGING MUTATIONS IN GENES INVOLVED IN SYNAPTIC FUNCTIONING. THESE RESULTS EXTEND UNDERSTANDING OF SCHIZOPHRENIA GENETICS, SPECIFICALLY SUPPORTING AN OLIGOGENIC SEVERE ALLELES MODEL AND A ROLE FOR RARE DAMAGING MUTATIONS IN GENES CRITICAL TO SYNAPTIC SIGNALING AND PLASTICITY. FOR THIS PROJECT, WE PROPOSE TO ENROLL AN ADDITIONAL 1250 CASES AND 1250 AGE- AND GENDER-MATCHED CONTROLS, ALL XHOSA-SPEAKING, BRINGING OUR TOTAL STUDY POPULATION TO 5425 PARTICIPANTS. WE WILL APPLY NEW GENOMIC TECHNOLOGY TO IDENTIFY PREVIOUSLY UNDETECTABLE CLASSES OF MUTATIONS LIKELY TO BE IMPLICATED IN SCHIZOPHRENIA. THE GENOMIC STRUCTURE OF XHOSA CASES AND CONTROLS WILL BE CHARACTERIZED USING WHOLE GENOME SEQUENCING (WGS), BOTH SHORT–READ ILLUMINA WGS TO IDENTIFY CONVENTIONAL CLASSES OF MUTATIONS AND (IN A SUBSET OF PARTICIPANTS WITH EXISTING CELL LINES) LONG-READ PACBIO WGS TO IDENTIFY STRUCTURAL VARIANTS OF ALL TYPES, MOBILE TRANSPOSABLE ELEMENTS, AND REPEAT EXPANSIONS. IN ADDITION, SAX V2, THE AFRICAN-VARIATION-ENRICHED SNP ARRAY DEVELOPED FOR THIS PROJECT BY AFFYMETRIX, WILL BE USED TO IDENTIFY COPY NUMBER VARIANTS (CNVS). AFRICA IS THE SINGLE MOST INFORMATIVE CONTINENT FOR UNDERSTANDING THE HUMAN GENOME AND HUMAN DISORDERS WITH WORLDWIDE IMPACT. AFRICAN POPULATIONS PROVIDE THE MOST COMPLETE HUMAN REFERENCE GENOMES FOR SCREENING CANDIDATE RISK ALLELES FOR ANY PHENOTYPE. THE WHOLE-GENOME SEQUENCING STRATEGIES USED IN THIS PROJECT ALLOW THE COMPARISON OF ALL CLASSES OF DAMAGING MUTATIONS BETWEEN CASES AND CONTROLS, INCLUDING THE DETECTION OF CASE-SPECIFIC COPY NUMBER VARIATION AND REPEAT EXPANSIONS, WHILE ALSO PROVIDING A RESOURCE FOR HUMAN GENOMICS RESEARCH WORLDWIDE.

TAS::57 3600::TAS AIR FORCE CENTER OF EXCELLENCE ON NATURE INSPIRED FLIGHT TECHNOLOGIES AND IDEAS

NN/LM REGION 6 RML AND NN/LM EVALUATION OFFICE (NEO)

NEW START COOPERATIVE AGREEMENT FOR IARPA TARGETED EVALUATION OF IONIZING RADIATION EXPOSURE-TEI-REX PROGRAM WITH UNIVERSITY OF WASHINGTON