Project Grant DP2GM149548
- This Project Grant award of $306,700 from the National Institute of General Medical Sciences (NIGMS), under the Biomedical Research and Research Training program (CFDA 93.859), aims to develop a novel, scalable, and cost-effective spatial biology platform for protein profiling. The platform will enable sub-cellular resolution analysis of protein presence and abundance using proprietary barcoded tags and an isothermal workflow. The key goals of the project are to: 1) demonstrate a semi-ordered...
- This Project Grant award of $453,750 from the National Institute of General Medical Sciences (NIGMS), under the Biomedical Research and Research Training program (CFDA 93.859), will fund research to develop advanced mass spectrometry-based proteomics technologies. The goal is to improve the depth, throughput, and accuracy of proteome-wide protein abundance, post-translational modification, and cysteine profiling. The research will leverage state-of-the-art mass spectrometry instrumentation to...
- This Project Grant award from the National Institute of General Medical Sciences (NIGMS), under the Biomedical Research and Research Training program (CFDA 93.859), supports the development of engineered enzymes that can be activated to perform targeted modifications of cellular proteins. The $1,602,000 award to the Dana-Farber Cancer Institute, Inc. (DFCI) will fund research to design and apply novel autoinhibited enzymes that can toggle between inactive and active conformations in response...
- This Project Grant award from the National Institute of General Medical Sciences (NIGMS), under the Biomedical Research and Research Training program (CFDA 93.859), provides $202,274 to develop an easy-to-use computer program for predicting the structure and degrading efficiency of proteolysis targeting chimeras (PROTACs). PROTACs are heterobifunctional molecules that induce the degradation of target proteins by recruiting them to E3 ubiquitin ligases. The awarded project aims to implement a...
- This Project Grant award from the National Institute of General Medical Sciences (NIGMS), under the Biomedical Research and Research Training program (CFDA 93.859), provides $350,000 in funding to Electronic Biosciences, Inc. to develop and demonstrate a novel enzyme-based, single-molecule protein sequencing system. The proposed technology aims to leverage enzymatic processing and advanced bioinformatics to achieve high accuracy and throughput in sequencing proteins, including those with...
- This federal Project Grant award of $335,712.00, awarded by the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859), supports the development of advanced imaging tools and data analysis techniques for studying protein interactions and organizations in cells at high spatiotemporal resolution. The key products and services to be delivered under this five-year project include: 1) Developing a high-resolution two-color...
- This $531,227 CAREER award from the National Science Foundation's (NSF) Engineering program to the University of California, Irvine (UC Irvine) aims to develop a new "OptOGel Proteomics" technique for high-resolution analysis of subcellular protein localization and function. The project will focus initial validation on mapping the nuclear lamina, a cellular structure implicated in cancer and aging. The research seeks to overcome limitations of current spatial proteomics tools by...
- The National Center for Translational and Developmental Proteomics (NCTDP) was awarded a $1,761,867 Project Grant from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859). The goal of this 5-year award is to optimize and disseminate cutting-edge methods for proteoform discovery and measurement to the scientific community. The NCTDP will achieve this through three technology optimization projects to prepare the...
- This Project Grant award of $449,726.00 from the National Cancer Institute (CFDA 93.396 - Cancer Biology Research) to the University of Illinois aims to develop innovative tools for rapidly mapping dynamic changes in protein interactions within living cells. The goal is to enable the facile analysis of protein interaction changes occurring within one minute or less, which will significantly improve the sensitivity and temporal resolution of existing approaches. The project will explore three...
- This $2,527,500 project grant awarded by the National Institutes of Health (CFDA 93.859 Biomedical Research and Research Training program) to President and Fellows of Harvard College (Harvard Medical School) supports cutting-edge research in quantitative proteomics. The project aims to advance sample multiplexing technologies for mass spectrometry-based proteome analysis, which will enable higher throughput and more comprehensive profiling of protein expression, modifications, and function....
POST-TRANSLATIONAL MODIFICATION PROTEOMICS IN 4D: CHEMOENZYMATIC TOOLS TO MAP THE DYNAMIC SPATIAL ORGANIZATION OF EUKARYOTIC SIGNALING PATHWAYS - PROJECT SUMMARY/ABSTRACT SPATIAL ORGANIZATION AND TEMPORAL DYNAMICS ARE INHERENT PROPERTIES OF EUKARYOTIC CELL SIGNALING PATHWAYS. DYNAMIC CHANGES IN THE SUBCELLULAR LOCALIZATION OF PROTEINS ARE PROGRAMMED BY POST-TRANSLATIONAL MODIFICATIONS (PTMS), SUCH AS PHOSPHORYLATION AND PROTEOLYSIS, WHICH OCCUR IN RESPONSE TO BIOLOGICAL STIMULI. EUKARYOTIC SIGNALING PATHWAYS RELY ON THE INTRODUCTION OF PTMS TO SPECIFIC PROTEINS TO RAPIDLY CHANGE PROTEIN FUNCTION AND LOCALIZATION, ENABLING CELLS TO RESPOND TO CHANGING INTERNAL OR ENVIRONMENTAL CONDITIONS. HOWEVER, DESPITE THE IMPORTANCE OF SPATIAL ORGANIZATION AND TEMPORAL DYNAMICS IN BIOLOGICAL SIGNALING, CURRENT TECHNOLOGIES ARE UNABLE TO PROVIDE A SYSTEMS-LEVEL EXPERIMENTAL MAPPING OF THE DYNAMIC SUBCELLULAR LOCALIZATION OF POST-TRANSLATIONALLY MODIFIED PROTEINS. TO MEET THIS CHALLENGE, WE PROPOSE TO DEVELOP NEW METHODS FOR PTM PROTEOMICS WITH SUBCELLULAR SPATIAL AND TEMPORAL RESOLUTION BY ENGINEERING GENETICALLY TARGETABLE, PTM-SELECTIVE PROXIMITY LABELING ENZYMES. THESE ENZYMES WILL TAG POST-TRANSLATIONALLY MODIFIED PROTEINS IN SPECIFIC SUBCELLULAR LOCATIONS, ENABLING THEIR ENRICHMENT AND ANALYSIS WITH MASS SPECTROMETRY-BASED PROTEOMICS EXPERIMENTS FOR MAPPING PTMS WITH SPATIAL AND TEMPORAL RESOLUTION. WE WILL INITIALLY FOCUS ON TWO PERVASIVE PTMS, PROTEOLYSIS AND PHOSPHORYLATION, BOTH OF WHICH PLAY CRITICAL ROLES IN NUMEROUS BIOLOGICAL SIGNALING PATHWAYS RELEVANT TO HUMAN HEALTH AND DISEASE. WE WILL APPLY PROTEIN ENGINEERING APPROACHES TO DEVELOP THREE DISTINCT CLASSES OF ENZYMES FOR SPATIOTEMPORALLY RESOLVED CAPTURE OF PROTEOLYTIC NEO-C TERMINI, PHOSPHOSERINE/PHOSPHOTHREONINE, AND PHOSPHOTYROSINE, RESPECTIVELY. WE WILL DEPLOY THESE TOOLS TO DISSECT THE SPATIOTEMPORAL DYNAMICS OF PROTEOLYSIS DURING APOPTOSIS; PHOSPHORYLATION DURING GROWTH FACTOR SIGNALING; AND CROSSTALK BETWEEN PROTEOLYSIS AND PHOSPHORYLATION DURING THE CELLULAR DECISION BETWEEN LIFE AND DEATH. THE BIOLOGICAL PATHWAYS AND STATES THAT CAN BE PROBED WITH THE TOOLS THAT WE WILL DEVELOP ARE NEARLY LIMITLESS, ENSURING THAT THEY WILL HAVE A BROAD AND TRANSFORMATIVE IMPACT ACROSS THE BIOMEDICAL SCIENCES. COMPLETION OF THE PROPOSED WORK WILL TRANSFORM OUR UNDERSTANDING OF HOW CELLULAR SIGNALING UNFOLDS ACROSS SPACE AND TIME AND HAS THE POTENTIAL TO REVEAL NEW PARADIGMS FOR THERAPEUTIC INTERVENTION IN PTM-BASED SIGNALING PATHWAYS.
Mod # | Description | ReasonForModification | Federal Obligation | Date |
|---|---|---|---|---|
| Not listed | $885.4k | 8/7/25 | ||
| Not listed | $1.4m | 8/24/22 | ||
| Not listed | $1.4m | 8/24/22 |