is_active:

Yes

budget_end:

07/01/2026

date_added:

08/02/2025

agency_code:

NIH

fiscal_year:

2025

project_num:

1S10OD038273-01

award_amount:

$1,980,309.00

budget_start:

08/01/2025

org_name:

YALE UNIVERSITY

org_state:

CT

org_country:

UNITED STATES

org_zipcode:

065208327

primary_duns:

043207562

abstract_text:

7. Project Summary/Abstract Funding is requested for the purchase of the current state-of-the-art Orbitrap Astral mass spectrometer system. The Orbitrap Astral is the newest hybrid (quadrupole/Orbitrap/Astral) MS platform in its class with a novel Astral mass analyzer capable of fragment ion scanning above 200 Hz at a resolution of 80,000 at m/z 524, a leading-edge Orbitrap mass analyzer which enables scan speeds of up to 40 Hz at resolution up to 480,000 at 200 m/z, and sub-part-per-million mass accuracy. The ability to parallelize precursor/fragment ion detection in the two mass analyzers along with the ultrafast scan rates offered by this cutting-edge instrument enable >5-fold more MS/MS scans/second as compared to the best mass spectrometers currently housed in the Keck MS & Proteomics Resource, enabling incredibly deep coverage from single-shot proteomics experiments. The Orbitrap Astral MS will be coupled to a Vanquish Neo UHPLC system that has excellent peak separation efficiency and reproducibility, and the proposed MS system will have all the necessary hardware and software needed for rapid identification, profiling, and quantitative proteomics workflows. Based on the manufacturer’s data, we expect this instrument will be able to identify over 9,000 proteins in a 15-minute LC gradient or 12,000 proteins in a 60-minute gradient for complex mammalian extracts. This unprecedented depth of coverage over short gradients would enormously improve the Resource’s sample throughput for biomarker discovery, helping to minimize the current 3+ week sample backlog and ensuring that the Resource has the state-of-the-art mass spectrometry capabilities to accommodate additional investigators who would benefit from these advanced technologies. Addition of the Orbitrap Astral will also substantially increase sensitivity for the identification of low-level proteins and their post translational modifications and allow the Resource to push the envelope of single-cell proteomics. The advances incorporated into this instrument make it the ideal platform to support the LFQ, DIA, and PTM workflows that have become highly-requested services by the 142+ Yale and non-Yale investigators submitting >7,668 samples to the MS & Proteomics Resource in FY23 and FY24 to date. This application is supported by 28 investigators encompassing 8+ different disciplinary research fields and 40+ different projects, and the proposed eight Major users of the Orbitrap Astral MS include members of four NIH and National Centers at Yale (the Yale/NIDA Neuroproteomics Center, the Yale Cancer Center, the Yale Alzheimer’s Disease Research Center, and the Interstitial Lung Disease Center of Excellence). The strengths of this proposal are manifold and include continued very strong institutional support not only in the initial committed investment (with >$227K committed towards service maintenance costs), but also in long-term assurances to cover any deficit that may occur for the Keck MS & Proteomics Resource; the sustained, balanced operational budget of the Resource; and the continued usage of and productive collaboration with the Resource by hundreds of NIH-funded investigators annually.

project_title:

Orbitrap Astral to support investigator proteomics research in a Core facility.

contact_pi_name:

LAM, TUKIET T

total_cost:

$1,980,309.00

is_active:

No

budget_end:

09/18/2019

date_added:

09/22/2018

agency_code:

NIH

fiscal_year:

2018

project_num:

1S10OD023651-01A1

award_amount:

$572,240.00

budget_start:

09/19/2018

org_name:

YALE UNIVERSITY

org_state:

CT

org_country:

UNITED STATES

org_zipcode:

065208327

primary_duns:

043207562

abstract_text:

7. Project Summary/Abstract Funding is requested toward the purchase of a Thermo Scientific Q-Exactive High Field Mass Spectrometer (Q-Exactive HF MS) system which would provide a uniquely high performance mass spectrometer for the MS & Proteomics Resource within the Keck Laboratory at Yale University. The Q-Exactive HF is one of the newest benchtop quadrupole-Orbitrap MS platforms in its class with a leading edge ultra-high- field Orbitrap analyzer which enables scan speed up to 18 Hz, resolution up to 240,000, and sub-parts-per- million mass accuracy, as well as superior ion transmission and isolation characteristics with its Advanced Active Beam Guide (AABG) design. These advanced features make the new HF platform twice as fast and 5 to 10-fold more sensitive than its predecessor, the Q-Exactive Plus. Our demo of the requested QE-HF mass spectrometer show an improvement of up to 42% in number of peptides ID, and greater than 23% improvements in the number of proteins ID from a complex brain proteome source compared to QE-Plus. This will enable investigators to reach deeper into the human and other complex proteomes than is currently possible. The advances incorporated into the Q-Exactive HF also make it the ideal platform to support the LFQ and PTM technologies that have become highly requested services by the 300+ Yale and 200+ non-Yale users and investigators at 85 institutions who have utilized the MS & Proteomics Resource over the last two years. The demand for these technologies supported by Q-Exactive Plus has increased so rapidly that there is a constant 3+ weeks backlog for data collection even though the instrument has been running at maximum capacity (>95% Accessible User Time, AUT). Addition of the requested Q-Exactive HF to this Resource would reduce this backlog, preventing unnecessary delays to biomedical research advancement, as well as ensure that the Resource has the capability to benefit even more investigators who would like to use the technologies for their biomedical research. This application is supported by 25 investigators and their collaborators encompassing more than 14 different disciplinary research fields at Yale and 4 other institutions including Mt. Sinai School of Medicine, Tufts University, University of Connecticut Health Center, and Medical University of South Carolina who propose to carry out >40 biomedical research projects with strong proteomics components that depend upon the requested instrumentation. The proposed Major users of the Q-Exactive HF MS include PI of four NIH and National Centers (i.e. VA-Yale National Center for PTSD, Yale/NIDA Neuroproteomics Center, Mount Sinai Conte Center on Epigenetic Mechanisms of Depression, and Yale Alzheimer's Disease Research Center). The strengths of this proposal are manifold and include continuing strong institutional support (e.g. providing >18% in cost sharing in this proposal to purchase the necessary liquid chromatography component); sustained balanced operational budget of the Resource; and the continued usage of and collaboration with the Resource by hundreds of NIH-funded investigators annually.

project_title:

High Resolution Tandem Mass Spectrometer to Meet Growing Demand for Proteomics at Yale

contact_pi_name:

LAM, TUKIET T

total_cost:

$572,240.00

is_active:

No

budget_end:

02/29/2016

date_added:

03/07/2015

agency_code:

NIH

fiscal_year:

2015

project_num:

1S10OD019967-01

award_amount:

$135,183.00

budget_start:

03/01/2015

org_name:

YALE UNIVERSITY

org_state:

CT

org_country:

UNITED STATES

org_zipcode:

065208327

primary_duns:

043207562

abstract_text:

 DESCRIPTION (provided by applicant): The Yale Keck MS and Proteomics Resource has developed and integrated a high throughput metabolomics workflow that utilizes the robustness of a high flow Ultra-Pressure Liquid Chromatography (UPLC) system in an emerging mass spectrometry based model. This model is for validating and quantifying metabolites and small molecules which provide a prospective classification and confirmation of bio-molecular markers from large clinical cohorts. As evident by the current instrument usage (based on the number of samples injected), our metabolomics workflow was immediately recognized by researchers at Yale and other institutions as an important biotechnological tool to efficiently and cost effectivey process their large study cohorts. Due to our development of these protocols utilizing a demo UPLC system, we are requesting funding to purchase a permanent ACQUITY UPLC H-Class system to be coupled to our existing 4000 QTRAP mass spectrometer which is the platform the metabolomics workflow was developed on. If funded, the permanent UPLC system would provide continued access with 83% instrument usage by the 7 Major NIH-funded users who supported this application, along with 11 Minor users utilizing the remaining >17% of the requested UPLC system. These investigators from Yale, 4 nearby (Harvard, Columbia University Medical Center, U.Conn Medical Center, and New York Medical College) and 2 other US (U. of Colorado at Denver and U. of Mississippi Medical Center) Institutions propose to use our Targeted metabolomics service to advance diverse biomedical research on: Diabetes, Obesity, Pulmonary Sarcoidosis, Corneal Antiangiogensis, Alcohol metabolism, Tissue injury, Melanoma, Neuronal Ceroid Lipofuscinosis, Autism, Lyme disease, Insulin resistance in Pregnancy, and Aging. The requested UPLC system will also enable our developed metabolomics workflow to be made available to the 218 investigators from 81 institutions and companies who used the services provided by the Yale Keck MS and Proteomics Resource in 2013. Progress in this metabolomics workflow will advance knowledge of how best to understand, prevent, prognose, and treat human diseases. The requested UPLC system and the associated metabolomics workflow would be unique at Yale University, and would be available to other interested investigators due to its placement in a core resource facility that accepts samples from across the U.S. and (when needed to keep its instrumentation operating at capacity) from around the world. Thus, the UPLC system would significantly contribute to biomedical research at Yale University and beyond.

project_title:

An Ultra-Performance Liquid Chromatography System to Support Metabolomics at Yale University

contact_pi_name:

LAM, TUKIET T

total_cost:

$135,183.00