Project Grant S10OD040074

A NEXT-GENERATION MASS SPECTROMETRY SYSTEM FOR ADVANCING QUANTITATIVE PROTEOME SCIENCE IN THE UPPER MIDWEST REGION - THE CENTER FOR METABOLOMICS AND PROTEOMICS (CMSP) REQUESTS FUNDING FOR A NEXT-GENERATION ORBITRAP ASTRAL MASS SPECTROMETRY (MS) SYSTEM. THIS INSTRUMENT WILL BE HOUSED IN THE CMSP CORE RESEARCH FACILITY, AN ACADEMIC RESEARCH SERVICES PROVIDER IN QUANTITATIVE MS-BASED PROTEOMICS TO DOZENS OF NIH-SUPPORTED RESEARCHERS AT THE UNIVERSITY OF MINNESOTA (UMN), AS WELL AS INVESTIGATORS FROM THE UPPER MIDWEST REGION AND INSTITUTIONS FROM ACROSS THE NATION. EXPERT PERSONNEL WITHIN THE WELL-SUPPORTED CMSP FACILITY WILL ENSURE THE ASTRAL MASS SPECTROMETER AND ACCOMPANYING ULTRA-HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (UHPLC) MODULE IS OPERATED AND MAINTAINED IN OPTIMUM CONDITION, AND ACCESSIBLE TO A LARGE COMMUNITY OF INVESTIGATORS RESEARCHING A WIDE VARIETY OF PRESSING ISSUES IN HUMAN HEALTH AND DISEASE. THE ASTRAL WILL REPLACE AN ORBITRAP FUSION TRIBRID INSTRUMENT, PURCHASED IN 2013, WHICH CURRENTLY IS THE ONLY CMSP PLATFORM FULLY DEDICATED TO DATA-INDEPENDENT ACQUISITION (DIA), WHICH IS QUICKLY BECOMING THE STANDARD FOR SENSITIVE AND ACCURATE QUANTITATIVE PROTEOMICS. UNFORTUNATELY, THE OUTDATED ORBITRAP FUSION SYSTEM LACKS PERFORMANCE CAPABILITIES THAT MEET THE NEEDS OF MOST INVESTIGATOR PROJECTS, WITH LIMITATIONS IN THROUGHPUT, SENSITIVITY AND DEPTH OF QUANTITATIVE RESULTS THAT ARE ACHIEVABLE. CONSEQUENTLY, MANY INVESTIGATORS SETTLE FOR TIME-CONSUMING AND MORE COSTLY APPROACHES TO MAXIMIZE DEPTH OF RESULTS, WHICH STILL FALL SHORT OF WHAT IS POSSIBLE WITH THE NEW ASTRAL MS SYSTEM. IN OTHER CASES, INVESTIGATORS CHOOSE NOT TO PURSUE OTHERWISE VALUABLE STUDIES USING QUANTITATIVE MS-BASED PROTEOMICS, DUE TO THE PROHIBITIVE TIME AND COST REQUIRED, AS WELL AS THE LIMITED SCOPE OF RESULTS ACHIEVABLE WITH CURRENT INSTRUMENTATION IN THE CMSP. THE NEW ASTRAL SYSTEM OFFERS A NEW WAY FORWARD. USING FAST RUN TIMES (30 MINUTES OR LESS) IT ACHIEVES PROTEOME-WIDE DEPTH DETECTION AND QUANTIFICATION IN COMPLEX CLINICALLY RELEVANT SAMPLES AND LOW-INPUT SAMPLES DERIVED FROM LIMITED AMOUNTS OF BIOLOGICAL MATERIAL. AS SUCH, THE ASTRAL WILL MEET THE REQUIREMENTS OF CMSP INVESTIGATORS AND THEIR NIH-SUPPORTED PROJECTS, WHICH FALL INTO THESE GENERAL APPLICATION AREAS: 1) HIGH-THROUGHPUT CLINICAL TRANSLATIONAL STUDIES OF LARGE SAMPLE COHORTS; 2) LOW-INPUT SAMPLES FROM MATERIAL-LIMITED SOURCES; 3) ROBUST COMPLEX MIXTURE QUANTIFICATION IN CLINICALLY RELEVANT SAMPLES. WE DESCRIBE 24 USER PROJECTS, PRIMARILY NIH-FUNDED, AND INCLUDING PROJECTS FROM EARLY CAREER FACULTY, WHICH WILL IMMEDIATELY BENEFIT FROM THE NEW ASTRAL SYSTEM, AS WE DEMONSTRATE FROM ANALYSIS OF REPRESENTATIVE SAMPLES USING THIS ADVANCED INSTRUMENTATION. BEYOND THESE IMMEDIATE IMPACTS, GIVEN CMSP'S REGIONAL AND NATIONAL REPUTATION, THE NEW ASTRAL SYSTEM WILL CATALYZE MANY MORE FUTURE PROJECTS FOR ADVANCING RESEARCH, OFFERING CAPABILITIES IN NEW AND EMERGING AREAS OF PROTEOME SCIENCE, INCLUDING DEEP PLASMA PROTEOMICS AND SINGLE CELL APPLICATIONS. THE UPSHOT OF THE ASTRAL SYSTEM HOUSED IN THE CMSP WILL BE NEW DISCOVERIES ACROSS A WIDE VARIETY OF RESEARCH AREAS AIMED AT IMPROVING HUMAN HEALTH AND MINIMIZING DEATH AND SUFFERING FROM DISEASE.