AMRC Core Director: Jonathan Brestoff, MD, PhD
AMRC Associate Director: Clay Semenkovich, MD
AMRC Assistant Director: Rita Brookheart, PhD
AMRC Metabolic Imaging Sub-Core Director: Gary Patti, PhD
AMRC Lab Manager: Sangeeta Adak, PhD
Phone: 314-747-8282
Email: sadak@wustl.edu
Mission
Wet lab space (600 square feet) designated for the Animal Model Research Core (AMRC) is located on the 8th floor of the Southwest Tower Building and can be reached by most NORC members by a short 5 to 10 minute walk through adjoining hallways and a 2nd floor pedestrian link that connects major research buildings. Here, mouse and tissue phenotyping is conducted. In the Clinical Science Research Building, 1100 square feet is dedicated to whole body composition by MRI, indirect calorimetry by TSE Phenomaster/Labmaster System, and treadmill exercise studies. PET/CT and PET/MR are located on the 1st floor of the East Imaging Building. This facility is 2820 square feet and contains all the instrumentation required for substrate uptake and metabolism and exosome biodistribution, animal housing for radioactive material (RAM) decay, image-analysis stations for facility users, and animal physiological monitoring equipment.
Over the past several decades, advances in genetic engineering of rodent models have greatly facilitated the use of these tractable models to study nutrition, obesity, and related metabolic diseases. The use of mice and rats has advanced our understanding of pathogenic mechanisms and allowed for early-stage preclinical testing of potential therapeutic agents. However, sophisticated metabolic phenotyping can be technically challenging and require use of expensive instrumentation that is beyond the financial means of an individual investigator.
The Animal Model Research Core (AMRC) has an overall goal of enabling animal research related to nutrition and obesity and to provide mechanistic insight into human disease by provision of consultation, training, and sophisticated instrumentation and services for mouse phenotyping.
This goal is pursued through two specific aims:
Specific Aim 1: To provide NORC investigators with key phenotyping services needed for nutrition/obesity-related research in animal models, including:
- High-precision standardized biochemical assays in serum and tissues, including triglycerides, cholesterol, and free fatty acids
- Body composition analysis
- Spontaneous activity, food intake, energy expenditure and energy balance using indirect calorimetry
- Evaluation of exercise endurance and its effects on metabolism
- Mass-spectrometry analysis for plasma and tissue metabolomics and lipidomics and plasma proteomics
- Mass spectrometry analysis of biospecimens collected after metabolic tracer infusion or ingestion with metabolomic analysis of blood and tissue samples by to determine tracer enrichment in metabolic substrates and macromolecules
Specific Aim 2: To provide consultation in experimental design and optimal use of AMR Core services for specific research projects, and training in procedures, assays, and use of instrumentation for investigators or their staff, in a broad range of technologies that facilitate the testing of hypotheses relevant to nutrition and obesity.
These aims encompass detailed animal phenotypic characterization, technologies that employ automation and large batches, complex instrumentation, and service and training in the pursuit of transformational research outcomes to improve human health.
Equipment
Key instrumentation required for listed services includes:
- 1 Synergy 4 Multi-mode Micro Optical plate reader adapted for high throughput determination of serum chemistries
- 1 GE Healthcare Life Sciences ÄKTA go protein purification system, purchased with institutional funds to support the Core in January 2020. This device uses two size exclusion columns in series for the separation of mouse lipoproteins and other proteins
- Several types of centrifuges
- 2 ECHO MRI machine and associated instrumentation. These devices noninvasively provides quantitation of body composition
- 1 PIXImus small animal DEXA for body composition (preferred by some bone biologists for coincident longitudinal assessment of bone density)
- 1 TSE Phenomaster (high-throughput phenotyping platform for fully automated and synchronized metabolic, behavioral, and physiological monitoring – 8 animals can be monitored at one time)
- 1 TSE PhenoMaster NG (next generation high-throughput phenotyping platform for fully automated and synchronized metabolic, behavioral, and physiological monitoring). This instrument is housed in an environmental chamber allowing investigators to modulate environmental temperature and light cycles. 16 animals can be monitored at one time
- 1 Columbus Instruments CLAMS system (high-throughput phenotyping platform for fully automated and synchronized metabolic, behavioral, and physiological monitoring). This instrument is housed in an environmental chamber allowing investigators to modulate environmental temperature and light cycles. 16 animals can be monitored at one time
- 8 additional wire-bottomed metabolic cages that are compatible with the Phenomaster system for determination of food intake and collection of excreta
- Infrared thermal camera, FLIR ONE
- 1 motorized treadmill from Columbus Instruments (#1055-SRM-D64), six-lane with shock grid and auto-calibration. This instrument was purchased new in 2019
- 1 Columbus Instruments motorized treadmill (Exer-3/6 treadmill), six-lane without shock grid. This machine is appropriate for endurance training experiments requiring daily use
- The TSE PhenoMaster NG system also has a two-lane treadmill and cages each containing running wheels to allow assessment of respiratory rates and RER during exercise (treadmill or voluntary wheel running).
- 1 swim tank, holds up to 8 mice and generates light current to stimulate the desire to swim
- Thermo Scientific TSQ Altis
- Orbitrap ID-X Tribrid mass spectrometer
- Agilent QTOF 6540
- Agilent QTOF 6545
- Agilent QTOF 6546
- Agilent Revident
- 1 Leica CM 1850 Cryostat
- 1 Columbus Instruments NIBP-8 Non-Invasive (tail cuff) blood pressure monitor
- 6 PA-C10 transmitters and receivers for telemetry determination of blood pressure
- 6 TA10TA-F20 transmitters for core temperature determination
- 1 Perimed Periscan laser Doppler imaging system for measuring blood flow in living animals
- 1 high resolution digital camera attached to a microscope and integrated with a computerized image processing system
- A variety of microscopes
- A variety of infusion pumps
- Study design and training in mouse metabolic phenotyping methods
- Biochemical assays (plasma)
- Plasma triglycerides
- Plasma cholesterol
- Plasma glucose
- Plasma non-esterified fatty acids
- Plasma lipoproteins (VLDL, LDL, HDL)
- Biochemical assays (tissues)
- Tissue triglycerides
- Tissue cholesterol
- Tissue non-esterified fatty acids
- Body composition analyses
- Determination of lean and fat mass by EchoMRI
- Metabolic assessment and comprehensive phenotyping capabilities
- Indirect calorimetry and energy balance
- Food intake
- Spontaneous activity
- Urine and feces collection
- Physical activity measurements
- Determination of cold tolerance or ability to acclimate
- Evaluation of exercise endurance and metabolic effects of exercise training in animal models on motorized treadmills or exercise wheels (voluntary)
- Metabolomics and stable isotope tracing
- Untargeted metabolomics, lipidomics, and proteomics with bioinformatics analysis
- Consultation on the design and implementation of a stable isotope tracer studies that can be coupled to targeted metabolomics to assess metabolic flux
Please contact Sangeeta Adak for core pricing information: sadak@wustl.edu.
Please acknowledge the Washington University NORC, Nutrition Obesity Research Center, in your publications by: “Supported by NIH grant P30 DK056341 (Nutrition Obesity Research Center).”