# Development of an Integrated Intermediary Metabolomics and Metabolic Flux Core

> **NIH NIH S10** · YALE UNIVERSITY · 2022 · $366,335

## Abstract

Project Summary
This proposal seeks funding for a Liquid Chromatography (LC), Differential Mobility Spectroscopy (DMS),
Quadrupole Time of Flight (LC-DMS-QToF) SCIEX 6600 mass spectrometer (AB Sciex LLC, Framingham, MA)
to build an integrated system describing the metabolic traffic in cells, plasma and tissues. The essential
endogenous biochemicals of life are confined to enzymatically delineated metabolic pathways shared across
most species. The collective flow of nutrient substrates into synthetic or catabolic pathways that best describes
key functions, transformations, differentiations, adaptations, or disease processes of a cell, tissue, or organism.
The challenge then is interpreting the flow form concentration data, since the concentration of a metabolite may
have little to do with its flow through a metabolic pathway. The lack of robust high-throughput analytical
techniques to assess the flow of metabolic traffic through these pathways is a major limitation to improving our
understanding of cellular and organismal physiology.
 Yale lacks a dedicated metabolomics core. The acquisition of the LC-DMS-QToF integrated system will
provide a core with: 1) a dedicated intermediary metabolomics platform on the KEGG metabolic map (CoMBI)
that through integrated omics can be reinforced by orthogonal transcriptomics, proteomics, phosphoproteomics
or genomics data sets, 2) an expansion of Mass Isotopomeric MultiOrdinate Flux Analysis (MIMOSA) developed
by my laboratory to quantitatively measure intracellular fluxes through sequential position-specific label transfer
of stable isotopes, and 3) an in vivo inter-tissue metabolic flux analysis designed for genetic screens of
metabolism. The combination of DMS with the high resolution and speed of ToF and mass fragmentation
minimize isobaric interference which otherwise plague stable isotope studies. We have had the opportunity of
having the requested instrument consigned to our laboratory at Yale through an academic/industry technology
alliance with SCIEX as a way to generate preliminary proof-of-principle data and establish our pipelines. A
bioinformatic alliance with Elucidata has developed a customized, open-sourced, cloud-based platform with an
intuitive user interface to support our unique computational demands. The instrument operates in our existing
Islet, Oxygen consumption, Mass Isotopomer flux Core analytical core (IOMIC) through chargebacks and with
institutional support at cost under an established, university-approved Internal Service Provider (ISP) account.
This unique and transformative platform will integrate the tens of 1000s of mass spectroscopic features, correct
for natural abundance, and track positional movement of mass labels through cells to generate a high resolution
“Google maps” of metabolism where the rate and direction of metabolic flow are quantified with demonstrated
application to microbiology, plants, fruit flies, cell culture, cancer and human tissue. These capabilities ar...

## Key facts

- **NIH application ID:** 10419697
- **Project number:** 1S10OD030370-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Richard G Kibbey
- **Activity code:** S10 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $366,335
- **Award type:** 1
- **Project period:** 2022-09-16 → 2023-09-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10419697

## Citation

> US National Institutes of Health, RePORTER application 10419697, Development of an Integrated Intermediary Metabolomics and Metabolic Flux Core (1S10OD030370-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10419697. Licensed CC0.

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