Metabolic Phenotyping Core

Human based nutrition and obesity research studies are generating data at an unparalleled pace. These data permit investigators to generate many disease-related hypotheses; however the sophisticated infrastructure needed to create disease-relevant models and the detailed metabolic technologies necessary to test these hypotheses lie outside the expertise of many individual research groups. Recent published works of core Co-Directors Alex Soukas and Robert Gerszten in Cell (PMID: 30929899) and the New England Journal of Medicine (PMID: 33289972) exemplify the translational work supported by this Core.

 

The goals of the Metabolic Phenotyping Core are to provide users with access to 1) expert consultative services on setting up studies in nutrition and metabolism, 2) high-quality model creation and sophisticated in silico data analysis and hypothesis generation and 3) state-of-the-art metabolic phenotyping.

Our ServicesOur Team

Core Services

Consultation:

  • Assistance with selecting appropriate methods to translate concept into hypothesis-testing research

  • Guidance on study design and methods to incorporate available Core techniques into grants and protocols

  • Use of in silico analyses to go from gene or genes to hypothesis to creation of a physiologically-relevant model.

  • Sophisticated Phe-WAS studies that permit association of gene variants, serum proteins, or serum metabolites across thousands of experimental paradigms permit an innumerable number of testable hypotheses to be arrived at by the core’s expert informaticians.

    Model Generation

    We can facilitate any of the following:

    • siRNA gene knockdown

    • shRNA lentiviral gene knockdown

    • Lentiviral gene overexpression

    • CRISPR based gene editing

    In any of the following cell types:

    • Primary hepatocyte cell culture

    • Immortalized cell culture

    • iPS-derived hepatocyte/adipocyte and fibroblast-derived adipocyte differentiation

    • User-provided iPS, primary, or immortalized cells

    Metabolic Phenotyping

    • Metabolomics for lipophilic or aqueous metabolites in candidate-based or unbiased discovery mode

    • GC-MS fatty acid profiling

    • mRNA and protein sample preparation

    • Targeted metabolic gene expression

    • Biochemical insulin signaling assays

    • Hepatocyte glucose output

    • Adipocyte glucose uptake

    • Seahorse mitochondrial assays

    • Murine body composition analysis (EchoMRI-100H)

    • Murine energy expenditure and behavioral analysis (Sable Promethion)

    Equipment

    Click for the full list of equipment

    • Echo-MRI 100H
    • Sable Promethion 16-cage indirect calorimetry apparatus in environmental chambers
    • XF24 and XF96 Seahourse Analyzers

    • Nikon SMZ800 dissecting microscopes

    • Nikon SMZ1500 dissecting microscope equipped with a UV light source for fluorescence microscopy with a mounted Canon Vixia HF M52 HD video camera

    • Zeiss Axioobserver A1 inverted microscope with micromanipulators for microinjection

    • MT Infors incubator for growth

    • 6-channel Clark electrode apparatus for oximetry and energy consumption measurements

    • Thermo Forma 3110 CO2 water jacketed tissue culture incubators

    • Zeiss inverted fluorescent microscope

    • Thermo RT1 refrigerated centrifuge outfitted with aerosol-resistant buckets.

    • High-throughput screening infrastructure capable of conducting fully automated measurement of morphological and fluorescently detected cellular phenotypes. (Fluorescence Leica DM6000 upright microscope with a motorized Prior 96-well stage, automated filter turret, automated objective head, high-speed, cooled CCD camera, automated image acquisition and analysis software (MetaMorph) and server-level workstation with RAID data storage)

    • Agilent 1260/6120 LC-MS system outfitted with a diode array detector, a Supelco 24-channel vacuum solid phase chromatography station for lipid class separation and an Agilent 6890 gas chromatograph mass spectrometer (GC/MS) equipped with a Supelcowax-10 column for detailed fatty acid analysis.

    • Ultra-high performance Thermo LC-MS/MS instruments

    • Triple quadrupole LC-MS/MS systems (AB/Sciex 5500, Waters Xevo-TQS, Thermo TSQ Quantiva)

    • Agilent Bravo robots, 2 of which have AssayMap heads for column work

    • Thermo Kingfisher 96 robot

    • Perkin Elmer Janus Automated Workstation.

    Tuesday June 8th, 2pm-5pm

     

    Dr. Soukas holds office hours on a quarterly basis for questions related to the services offered above. Zoom details can be requested via this inquiry form. 

    Interested in utilizing our services or equipment for a current or upcoming project? Fill out the inquiry form below.

    Core Leadership

    Alexander Soukas, MD, PhD

    Alexander Soukas, MD, PhD

    Co-Director of Metabolic Phenotyping Core
    Associate Professor of Medicine
    Massachusetts General Hospital, Center for Human Genetic Research
    CPZN6224, 185 Cambridge St.
    Boston, MA  02114
    asoukas@mgh.harvard.edu

    Robert Gerszten, MD

    Robert Gerszten, MD

    Co-Director of Metabolic Phenotyping Core
    Herman Dana Professor of Medicine
    Beth Israel Deaconess Medical Center
    330 Brookline Ave.
    Boston, MA  02215
    Phone: 617-661-7000
    rgerszten@bidmc.harvard.edu

    CENTER MEMBERS ARE REMINDED TO ACKNOWLEDGE THE NORCH GRANT CONTRIBUTION IN THEIR PUBLICATIONS (P30DK040561)