Development of Next Generation Mass Spectrometric Instrumentation for Proteomics

Information

  • Research Project
  • 10240528
  • ApplicationId
    10240528
  • Core Project Number
    R01GM136654
  • Full Project Number
    5R01GM136654-03
  • Serial Number
    136654
  • FOA Number
    RFA-RM-18-009
  • Sub Project Id
  • Project Start Date
    9/1/2019 - 4 years ago
  • Project End Date
    8/31/2024 - 2 months from now
  • Program Officer Name
    LIU, CHRISTINA
  • Budget Start Date
    9/1/2021 - 2 years ago
  • Budget End Date
    8/31/2022 - a year ago
  • Fiscal Year
    2021
  • Support Year
    03
  • Suffix
  • Award Notice Date
    8/16/2021 - 2 years ago
Organizations

Development of Next Generation Mass Spectrometric Instrumentation for Proteomics

Project Summary/Abstract Currently, most mass spectrometric (MS) analyses for proteomics are performed in sequential mode, wherein various species in a sample are selected and interrogated one after another. As a consequence of the finite time needed to examine each species in turn, sequential mode MS suffers from inescapable limitations in sensitivity, speed and ability to analyze all ions, especially when the composition of the ion beam is complex and rapidly changing. These limitations have kept vast tracts of biology and biomedicine, including, for example, deep single cell proteome analysis, out of reach of the current MS technology. In the present proposal, we posit that sensitivity, speed and dynamic range can be vastly improved by performing MS in parallel (by analogy to Next Generation DNA Sequencing), thus overcoming the technical barriers inherent to current commercial mass spectrometers that operate largely in sequential mode. Here, we propose to develop new MS instrumentation to execute MS in a massively parallel manner, with two major objectives in mind: Objective 1. Increase the sensitivity, speed and depth of proteome analyses by up to and ultimately beyond 1000-fold. The current sequential MS approaches can be likened to sampling the Niagara Falls with a bucket, where the majority of the sample is wasted. Our proposed parallel MS technology is designed to eliminate this immense waste. Objective 2. Filter noise in real time to eliminate unwanted ion background prior to MS analysis, thereby maximizing the MS utilization of the sample ions of interest and the resulting signal-to- noise ratios, as well as providing increased dynamic range to measure very low abundance components in the presence of highly abundant components. Successful attainment of these objectives will allow deep, comprehensive, high throughput analyses of proteomes in cases where sample availability is limiting, where the components of interest elude detection due to their low abundance, or when single cell analysis is needed to address the biological or biomedical question at hand. Success in this endeavor will propel forward many areas of basic and applied biomedical research that require proteomic analyses in a manner analogous to the immense progress that has been made through development of Next Generation DNA Sequencing.

IC Name
NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
  • Activity
    R01
  • Administering IC
    GM
  • Application Type
    5
  • Direct Cost Amount
    420819
  • Indirect Cost Amount
    288299
  • Total Cost
    709118
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    310
  • Ed Inst. Type
    GRADUATE SCHOOLS
  • Funding ICs
    OD:709118\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    ROCKEFELLER UNIVERSITY
  • Organization Department
    INTERNAL MEDICINE/MEDICINE
  • Organization DUNS
    071037113
  • Organization City
    NEW YORK
  • Organization State
    NY
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    100656399
  • Organization District
    UNITED STATES