University Of Washington

FY26 RDT AND E ACOUSTIC SYSTEMS TD 5101026APL/UW FY2020 - FY2025 REQUIREMENTS IN SUPPORT OF CLIN 0001UNIVERSITY AFFILIATED RESEARCH CENTER (UARC) EFFORT IN ACCORDANCE WITH SECTION C.

MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA) - TASK AREA A

LUNG TRANSPLANTATION SERVICES FOR PUGET SOUND HEALTH CARE SYSTEMS 5-YEAR BASE PLUSE ONE 1-YEAR OPTION

ENGINEERING SERVICES

THE UNIVERSITY OF WASHINGTON CRYO-EM GROUP (UW-CRYOEM), UNDER THE DIRECTION OF DAVID VEESLER, PH.D., WILL PERFORM THE FOLLOWING WORK TO SUPPORT THE BASIC PROJECT REQUIREMENT. UW-CRYOEM WILL BE RESPONSIBLE FOR SOLVING CRYOEM STRUCTURES DURING THIS CONTRACT YEAR (SEPT 1, 2024 THROUGH AUG 31, 2025). UW-CRYOEM MAY ALSO MANAGE (SHEPHERD) AND WILL SUPPORT OTHER SPECIAL STUDIES AS NEEDED. A. STRUCTURE DETERMINATION OF PROTEINS OR PROTEIN COMPLEXES BY CRYOEM: UW-CRYOEM (DR. VEESLER) WILL DETERMINE THE STRUCTURE OF PROTEIN OR PROTEIN COMPLEXES USING CRYOEM AS A PART OF THIS SUBCONTRACT. THESE TARGET(S) WILL ORIGINATE FROM NIAID CATEGORY A-C INFECTIOUS DISEASE ORGANISMS, AS WELL AS EMERGING AND RE-EMERGING DISEASE AND ONCE APPROVED BY NIAID WILL ENTER THE SSGCID PIPELINE FOR TRACKING THE UW-CRYOEM WORK. THE TARGETS SELECTED WILL BE IMPACTFUL AND MAY BE MANAGED AS HIGH VALUE TARGET (HVT), COMMUNITY REQUEST PROJECT (CRP), HIGHEST IMPACT PROJECT (HIP) AND OTHER SPECIAL STUDIES WITHIN THE SSGCID PIPELINE. PROTEINS FROM VIRAL AND/OR EUKARYOTIC TARGETS WILL BE EXPRESSED IN BACULOVIRUS-INFECTED INSECT CELLS OR MAMMALIAN CELLS (HEK), WHILE BACTERIAL TARGETS (IF SELECTED FOR CRYOEM) WILL BE EXPRESSED IN E. COLI. THE MOLECULAR WEIGHT AND STOICHIOMETRY OF THE PURIFIED PROTEINS WILL BE CONFIRMED USING ANALYTICAL SEC COUPLED WITH MULTI-ANGLE LIGHT SCATTERING (SEC-MALS). THE HOMOGENEITY AND STRUCTURAL STABILITY OF THE PURIFIED PROTEINS WILL ALSO BE ASSESSED BY HIGH-THROUGHPUT NEGATIVE STAIN ELECTRON MICROSCOPY USING AN AUTOMATED DATA COLLECTION AND PROCESSING PIPELINE. PROMISING SAMPLES WILL BE FURTHER EVALUATED BY COMPUTING LOW-RESOLUTION THREE-DIMENSIONAL RECONSTRUCTIONS THAT DEMONSTRATE THE COMPOSITIONAL AND CONFORMATIONAL HETEROGENEITY OF EACH SAMPLE. THIS INFORMATION CAN ALSO BE USED TO GUIDE FURTHER CONSTRUCT SELECTION AND OPTIMIZATION OF THE EXPRESSION AND PURIFICATION CONDITIONS (IF NECESSARY). SAMPLES WILL BE VITRIFIED WITH AN FEI VITROBOT DEVICE TO PLUNGE-FREEZE GRIDS IN LIQUID ETHANE UNDER CAREFULLY CONTROLLED CONDITIONS. THE CRYOEM EXPERIMENTS WILL BE CARRIED OUT ON A TITAN KRIOS ELECTRON MICROSCOPE, EQUIPPED WITH A GATAN GIF ENERGY FILTER AND A K2 SUMMIT DIRECT ELECTRON DETECTOR. AUTOMATED DATA ACQUISITION AND PROCESSING ALLOWS A STREAMLINING OF ALL THE STEPS INVOLVED IN STRUCTURE DETERMINATION BY CRYOEM AT NEAR-ATOMIC RESOLUTION. THE LEGINON DATA COLLECTION SOFTWARE RUNS CONTINUOUSLY; ENABLING AUTOMATED TARGETING AND IMAGE ACQUISITION. LEGINON IS INTEGRATED WITH APPION, A DATA PROCESSING PIPELINE THAT CONNECTS DATA ACQUISITION TO PROCESSING ON A LOCAL CLUSTER, PROVIDING A RELATIONAL DATABASE OF ALL MICROGRAPHS TO EXPEDITE SUBSEQUENT PROCESSING. APPION AUTOMATES MANY IMAGE PROCESSING TASKS AND CREATES A SMOOTH WORKFLOW THAT ALLOWS REAL-TIME ASSESSMENT OF DATA QUALITY DURING ACQUISITION AND PREVENTS ERRORS BY TRACKING ALL THE DETAILS RELATED TO IMAGE ACQUISITION AND PROCESSING. B. PANDEMIC PREPAREDNESS AND RAPID RESPONSE TO OUTBREAKS/EPIDEMIC/PANDEMICS: UW-CRYOEM WILL LEAD A STUDY ON THE COMPUTATIONAL DESIGN OF STABILIZED NIPAH VIRUS ATTACHMENT AND FUSION GLYCOPROTEINS. C. QUALITY CONTROL, DATA COLLECTION AND REPORTING: UW-CRYOEM WILL ESTABLISH AND CONDUCT QUALITY CONTROL PROCEDURES AS NECESSARY TO ENSURE THE PRODUCTION OF HIGH-QUALITY DATA. UW-CRYOEM WILL ENSURE THAT THE STATUS OF ALL WORK PERFORMED FOR SSGCID IS UPDATED IN A TIMELY FASHION, THROUGH THE CENTRAL TARGET TRACKING DATABASE (CTTDB), TRACKING SPREADSHEETS AND/OR ANY OTHER TRACKING SYSTEM REQUIRED BY THE PROJECT. DR. VEESLER AND/OR STAFF FROM UW-CRYOEM WILL PARTICIPATE IN SSGCID PROJECT MEETINGS AND NIAID-REQUIRED MEETINGS AS REQUIRED TO ENSURE THE SUCCESS OF THE PROJECT. DR. VEESLER AND/OR STAFF FOMR UW-CRYOEM WILL CONTRIBUTE TO QUARTERLY AND SEMI-ANNUAL PROGRESS REPORTS AND ANY OTHER NIAID REQUIRED REPORTS AS NEEDED AND IN A TIMELY FASHION AND WILL CONDUCT THE PROJECT WORK WITH THE AIM OF PRODUCING IMPACTFUL PUBLICATIONS. TAKEN TOGETHER IN PARTS A AND B ABOVE, TE

THE UNIVERSITY OF WASHINGTON CRYO-EM GROUP (UW-CRYOEM), UNDER THE DIRECTION OF DAVID VEESLER, PH.D., WILL PERFORM THE FOLLOWING WORK TO SUPPORT THE BASIC PROJECT REQUIREMENT. UW-CRYOEM WILL BE RESPONSIBLE FOR SOLVING CRYOEM STRUCTURES DURING THIS CONTRACT YEAR (SEPT 1, 2025 THROUGH AUG 31, 2026). UW-CRYOEM WILL ALSO MANAGE (SHEPHERD) A PANDEMIC PREPAREDNESS PROJECT AND WILL SUPPORT OTHER SPECIAL STUDIES AS NEEDED. A. STRUCTURE DETERMINATION OF PROTEINS OR PROTEIN COMPLEXES BY CRYOEM: UW-CRYOEM (DR. VEESLER) WILL DETERMINE THE STRUCTURE OF PROTEIN OR PROTEIN COMPLEXES USING CRYOEM AS A PART OF THIS SUBCONTRACT. THESE TARGET(S) WILL ORIGINATE FROM NIAID CATEGORY A-C INFECTIOUS DISEASE ORGANISMS, AS WELL AS EMERGING AND RE-EMERGING DISEASE AND ONCE APPROVED BY NIAID WILL ENTER THE SSGCID PIPELINE FOR TRACKING THE UW-CRYOEM WORK. THE TARGETS SELECTED WILL BE IMPACTFUL AND MAY BE MANAGED AS HIGH VALUE TARGET (HVT), COMMUNITY REQUEST PROJECT (CRP), HIGHEST IMPACT PROJECT (HIP) AND OTHER SPECIAL STUDIES WITHIN THE SSGCID PIPELINE. PROTEINS FROM VIRAL AND/OR EUKARYOTIC TARGETS WILL BE EXPRESSED IN BACULOVIRUS-INFECTED INSECT CELLS OR MAMMALIAN CELLS (HEK), WHILE BACTERIAL TARGETS (IF SELECTED FOR CRYOEM) WILL BE EXPRESSED IN E. COLI. THE MOLECULAR WEIGHT AND STOICHIOMETRY OF THE PURIFIED PROTEINS WILL BE CONFIRMED USING ANALYTICAL SEC COUPLED WITH MULTI-ANGLE LIGHT SCATTERING (SEC-MALS). THE HOMOGENEITY AND STRUCTURAL STABILITY OF THE PURIFIED PROTEINS WILL ALSO BE ASSESSED BY HIGH-THROUGHPUT NEGATIVE STAIN ELECTRON MICROSCOPY USING AN AUTOMATED DATA COLLECTION AND PROCESSING PIPELINE. PROMISING SAMPLES WILL BE FURTHER EVALUATED BY COMPUTING LOW-RESOLUTION THREE-DIMENSIONAL RECONSTRUCTIONS THAT DEMONSTRATE THE COMPOSITIONAL AND CONFORMATIONAL HETEROGENEITY OF EACH SAMPLE. THIS INFORMATION CAN ALSO BE USED TO GUIDE FURTHER CONSTRUCT SELECTION AND OPTIMIZATION OF THE EXPRESSION AND PURIFICATION CONDITIONS (IF NECESSARY). SAMPLES WILL BE VITRIFIED WITH AN FEI VITROBOT DEVICE TO PLUNGE-FREEZE GRIDS IN LIQUID ETHANE UNDER CAREFULLY CONTROLLED CONDITIONS. THE CRYOEM EXPERIMENTS WILL BE CARRIED OUT ON A TITAN KRIOS ELECTRON MICROSCOPE, EQUIPPED WITH A GATAN GIF ENERGY FILTER AND A K2 SUMMIT DIRECT ELECTRON DETECTOR. AUTOMATED DATA ACQUISITION AND PROCESSING ALLOWS A STREAMLINING OF ALL THE STEPS INVOLVED IN STRUCTURE DETERMINATION BY CRYOEM AT NEAR-ATOMIC RESOLUTION. THE LEGINON DATA COLLECTION SOFTWARE RUNS CONTINUOUSLY; ENABLING AUTOMATED TARGETING AND IMAGE ACQUISITION. LEGINON IS INTEGRATED WITH APPION, A DATA PROCESSING PIPELINE THAT CONNECTS DATA ACQUISITION TO PROCESSING ON A LOCAL CLUSTER, PROVIDING A RELATIONAL DATABASE OF ALL MICROGRAPHS TO EXPEDITE SUBSEQUENT PROCESSING. APPION AUTOMATES MANY IMAGE PROCESSING TASKS AND CREATES A SMOOTH WORKFLOW THAT ALLOWS REAL-TIME ASSESSMENT OF DATA QUALITY DURING ACQUISITION AND PREVENTS ERRORS BY TRACKING ALL THE DETAILS RELATED TO IMAGE ACQUISITION AND PROCESSING. B. PANDEMIC PREPAREDNESS AND RAPID RESPONSE TO OUTBREAKS/EPIDEMIC/PANDEMICS: UW-CRYOEM WILL LEAD A STUDY ENTITLED “MARBURG VIRUS GLYCOPROTEIN CHARACTERIZATION FOR ANTIGEN DESIGN.” C. QUALITY CONTROL, DATA COLLECTION AND REPORTING: UW-CRYOEM WILL ESTABLISH AND CONDUCT QUALITY CONTROL PROCEDURES AS NECESSARY TO ENSURE THE PRODUCTION OF HIGH-QUALITY DATA. UW-CRYOEM WILL ENSURE THAT THE STATUS OF ALL WORK PERFORMED FOR SSGCID IS UPDATED IN A TIMELY FASHION, THROUGH THE CENTRAL TARGET TRACKING DATABASE (CTTDB), TRACKING SPREADSHEETS AND/OR ANY OTHER TRACKING SYSTEM REQUIRED BY THE PROJECT. DR. VEESLER AND/OR STAFF FROM UW-CRYOEM WILL PARTICIPATE IN SSGCID PROJECT MEETINGS AND NIAID-REQUIRED MEETINGS AS REQUIRED TO ENSURE THE SUCCESS OF THE PROJECT. DR. VEESLER AND/OR STAFF FOMR UW-CRYOEM WILL CONTRIBUTE TO QUARTERLY AND SEMI-ANNUAL PROGRESS REPORTS AND ANY OTHER NIAID REQUIRED REPORTS AS NEEDED AND IN A TIMELY FASHION AND WILL CONDUCT THE PROJECT WORK WITH THE AIM OF PRODUCING IMPACTFUL PUBLICATIONS. TAKEN TOGETHER IN PARTS A AND B ABOVE

A NEW NETWORK OF HOUSEHOLD TRANSMISSION STUDIES FOR VACCINE EFFECTIVENESS EVALUATIONS

THE PROPOSED STUDIES WILL FOCUS ON DEVELOPMENT OF AN ADJUVANTED VACCINE FORMULATION TARGETING FENTANYL, FENTANYL ANALOGS, HEROIN, HEROIN ANALOGS, OR MIXTURES OF HEROIN/FENTANYL THROUGH EITHER SINGLE-VALENT OR MULTI-VALENT VACCINE STRATEGIES. THESE VACCINES WILL BE INITIALLY SCREENED IN MICE FOR IMMUNOGENICITY, AND THEN TESTED FOR EFFICACY IN REDUCING OPIOID DISTRIBUTION TO THE BRAIN, AND FOR REDUCING OPIOID-INDUCED ANTINOCICEPTION, RESPIRATORY DEPRESSION AND BRADYCARDIA IN RATS AND MINIATURE PIGS (MINI-PIGS). ALL STUDIES INVOLVING MICE AND RATS WILL BE CONDUCTED IN THE LABORATORY OF DR. PRAVETONI LOCATED IN EITHER THE DEPARTMENT OF PSYCHIATRY & BEHAVIORAL SCIENCES AT THE UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE, OR AT HIS FORMER AFFILIATION THE DEPARTMENT OF PHARMACOLOGY AT THE UNIVERSITY OF MINNESOTA MEDICAL SCHOOL. DR. PRAVETONI WILL SUPERVISE STUDIES INVOLVING MINI-PIGS, WHICH WILL BE CONDUCTED AT THE UNIVERSITY OF MINNESOTA COLLEGE OF VETERINARY MEDICINE AND SUPERVISED BY DR. ALONSO GUEDES, DVM, PHD. BOTH THE UNIVERSITY OF WASHINGTON AND UNIVERSITY OF MINNESOTA HAVE AAALAC-ACCREDITED FACILITIES AND COMPLY TO THE GUIDELINES OF THEIR RESPECTIVE INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE (IACUC). DR. PRAVETONI WILL BE RESPONSIBLE FOR ANIMAL STUDIES AND IACUC COMPLIANCE AT ALL SITES. DR. PRAVETONI€„¢S TEAM WILL ALSO MANAGE CDMO ACTIVITIES AT CAMBREX AND GBI TO MANUFACTURE GMP GRADE MATERIALS.

"UNDER THE LEADERSHIP OF CO-PI DR. CHU, THE UNIVERSITY OF WASHINGTON (UW) STUDY TEAM WILL EXECUTE THIS STUDY IN COLLABORATION WITH PRIME RECIPIENT AND CO-PI DR. NALEWAY€„¢S TEAM AT THE KAISER PERMANENTE CENTER FOR HEALTH RESEARCH (KPCHR). ESTABLISH A COMMON PROTOCOL IN COLLABORATION WITH KPCHR, CDC AND OTHER SITES (IF RELEVANT), ESTABLISH A COMMON PROTOCOL FOR THIS PROSPECTIVE COHORT STUDY. THE COMMON PROTOCOL WILL DESCRIBE REQUIRED ELEMENTS FOR STUDY ENROLLMENT, DATA/SPECIMEN COLLECTION, INCLUDING DATA COLLECTION TOOLS, AND LABORATORY TESTING. OBTAIN INSTITUTIONAL REVIEW BOARD APPROVAL OBTAIN INSTITUTIONAL REVIEW BOARD (IRB) APPROVAL FOR ALL STUDY ACTIVITIES BEFORE INITIATING CONTACT WITH POTENTIAL PARTICIPANTS. THE KPNW IRB WILL SERVE AS THE SINGLE IRB OF RECORD FOR THE STUDY. THE IRB REVIEW WILL INCLUDE REVIEW OF ALL PARTICIPANT-FACING STUDY MATERIALS INCLUDING ENROLLMENT MATERIALS AND INFORMED CONSENT AND HIPAA AUTHORIZATION. IRB APPROVAL WILL BE RENEWED ANNUALLY AND WILL BE MODIFIED AS NECESSARY FOR CHANGING STUDY CONDITIONS. THE UW STUDY TEAM WILL FOLLOW AGREED-UPON PROCEDURES FOR SUBSEQUENT STUDY MODIFICATION TO THE IRB. THE UW STUDY TEAM WILL TRACK ALL STUDY DEVIATIONS AND ADVERSE EVENTS FOR THEIR SITE. DEVIATIONS AND ADVERSE EVENTS WILL BE REPORTED TO KPCHR ANNUALLY PRIOR TO CONTINUING REVIEW OR IMMEDIATELY IF THE UW PI DETERMINES THEY MEET PROMPT REPORTING REQUIREMENTS. THE UW TEAM WILL DOCUMENT PI DETERMINATION OF WHETHER DEVIATIONS OR EVENTS ARE SUBJECT TO PROMPT REPORTING REQUIREMENTS ACCORDING TO KP IRB POLICIES"

DEVELOPMENT OF NOVEL STING PATHWAY AGONISTS AS VACCINE ADJUVANTS

"IVY 5 - SURVEILLANCE OF ACUTELY ILL ADULTS WITH RESPIRATORY VIRUSES, INCLUDING SARS-COV-2 "