Cores & Support Services
NIDDK internal lab and branch staff have access to the cores and support services below. Cores and support services offer cutting-edge technology and consultative services that aim to improve research quality and cost efficiency.
Current NIH staff can view additional services through the NIH Collaborative Research Exchange (CREx) (login required).
Advanced Light Microscopy and Image Analysis Core
Jeff Reece, M.S., Director
The importance of light microscopy to biomedical research is exemplified by the awarding of two Noble Prizes in the past decade to advances-- fluorescent proteins, and super-resolution - that are virtually subsets of fluorescence microscopy. The mission of the NIDDK Advanced Light Microscopy & Image Analysis Core (ALMIAC) is thus to provide NIDDK researchers and their collaborators with tools and training in the latest technologies and techniques associated with light microscopy (LM), particularly 3D fluorescence microscopy. The ALMIAC is an educator and enabler rather than a service provider, so that users can fully absorb and apply the concepts to their research projects, while gaining valuable hands-on experience. To fulfill its mission, the NIDDK ALMIAC provides these resources:
- Instrumentation and training to those NIDDK researchers that do not otherwise have easy access to both. Current microscopes include point-scanning confocal, total internal reflection florescence (TIRF), and ground state depletion (GSD) super-resolution. These are supplemented with a high-end image analysis workstation, and a network file server for long-term storage of images. Training is via scheduled one-on-one sessions.
- Support for NIDDK labs/branches that have/need LM equipment. Occasionally the expertise available in the ALMIAC is useful when making new imaging equipment purchases, and using the equipment after it arrives.
- Liaison to equipment outside NIDDK, when the ALMIAC or other NIDDK labs do not have the optimal equipment. Almost always when this situation arises, the equipment can be found at another Institute here on the Bethesda campus.
If you work at NIDDK and wish to use ALMIAC resources, please contact Jeff Reece.
Advanced Mass Spectrometry Core
The Advanced Mass Spectrometry Core assists the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) investigators with a wide range of mass spectrometry applications, including basic quality control, general problem solving during the development of complex experimental approaches, and discovery work. In each application, mass spectrometers are involved directly in obtaining important project answers.
Mass spectrometry detects molecules without specialized molecule-specific reagents. This makes it an unbeatable tool for rapid and tailored problem solving.
The types of analyses we perform are diverse and can include activities ranging from intact mass measurements of small molecules to proteins over 100kD. Peptide-centric experiments involving protein identification and isotope-aided, relative quantitative comparisons can be used to observe differences in protein abundance or a post-translational state between two or more samples containing hundreds or thousands of proteins. However, “off-menu” solutions to unique problems brought to us by principal investigators are among our most exciting puzzles, and such problems are especially sought. We use minimal cost recovery for the NIDDK to make analysis sustainable. Non-NIDDK federal projects with cost recovery, which is very competitive with outsourcing, are also possible. The first step of consideration for any analysis is to contact staff before samples are created.
The Biotechnology Core specializes in large-scale production and purification of biological materials from various sources to advance research in fields such as vaccine development, drug development, and structural biology. To achieve this goal, the laboratory integrates two main functions: (1) production of biologics, conducted in a multipurpose, state-of-the-art production facility, and (2) research and process development related to solving biological production issues by utilizing physiological, molecular biology, and technical approaches.
The lab has successfully solved a variety of production challenges. These include growing large amounts of different microorganisms, mammalian cells, and insect cells, and obtaining bulk and purified proteins from large amounts of media and biomass. Scientists achieved this by utilizing physiological, molecular biology, and technical approaches specific to each producer and product. Examples of molecule production for structural studies include the following: (1) toll-like receptor 3 by transiently infected insect cells, (2) G protein-coupled neurotensin receptor (NTS1) from recombinant E. coli and from stably transfected HEK 293 cells, and (3) capsular polysaccharides of Neisseria meningitidies from E. coli. Examples of production of molecules, microorganisms and cells for therapeutic and vaccine studies include cell wall and peptydoglycan from Bacillus anthracis, Shigella, and recombinant malaria transmission blocking vaccine Pfs 25h. The laboratory conducts research on modifying adhesion properties of mammalian cells (for virus production) and on improving the growth properties of recombinant E. coli strains (for recombinant protein production).
Clinical Laboratory Core
Mary Walter, Ph.D., Director
Scientists in the Clinical Laboratory Core collaborate with investigators from across the Clinical Research Program to provide sensitive, inexpensive, and reproducible analyses. We also develop new assays and support a wide range of clinical studies in the fields of endocrinology, hepatology, nephrology, and metabolism. These analyses include measurement of gut hormones, adipokines, oxidative stress markers, cytokines, and other biomarkers in biologic fluids that are related to diabetes, endocrine, and metabolic research. The Laboratory has added new hormone assays to reflect the current research trends, as well as the Luminex technology, which has greatly expanded our analytical capabilities. The Laboratory performs extensive validation of all assays before conducting routine sample analyses of clinical specimens. After assay validation, the Laboratory coordinates with clinical research investigators to establish a charge-back fee structure. This structure supports ongoing and routine specimen analyses, charging for the cost of supplies only. Additionally, the Laboratory works to reduce costs of assays by centralizing the purchase of common supplies used in specimen analyses and by taking advantage of bulk purchasing discounts. This approach yields savings that are passed along to the investigators utilizing the Laboratory’s services. Assays are uniquely tailored to meet the needs of the investigator, thus saving on sample volume and promoting cost efficiency in all cases.
The Clinical Laboratory Core also provides a service that allows for simple access to human sample acquisition, processing, tracking, and storage in accordance with current legislation. The acquisition process involves preparation of tubes for blood draw to achieve the lowest levels of degradation. Samples are processed within 1 hour of blood collection to ensure thermal preservation. The Laboratory recently purchased a new specimen-tracking database. This web-based tool is customizable and provides quick, reliable, and accurate accounting for clinical specimens stored with the Clinical Laboratory Core.
Clinical Mass Spectrometry Core
Peter J. Walter, Ph.D., Director
The mission of the NIDDK’s Clinical Mass Spectrometry Core (CMSC) is to collaborate with investigators from NIDDK and other institutes within NIH on quantitative mass spectrometry analyses. This includes the analysis of stable isotope tracer studies, doubly labeled water, drugs and drug metabolites, and small molecules by liquid chromatography–mass spectrometry (LC-MS), gas chromatography–mass spectrometry (GC-MS) and isotope ratio mass spectrometry (IRMS).
The CMSC was initially established to support all stable isotope applications in NIDDK’s clinical labs and to advise, develop, and validate novel stable isotope-labeled research assays in collaboration with ongoing clinical research projects. Our primary emphasis was on the clinical measurement of total energy expenditure (TEE) by doubly labeled water (DLW). TEE is the total energy a person or animal uses in a day for activities, including rest. TEE is an important calculation used in determining dietary and exercise needs. It has been used extensively in obesity research.
Currently, one of the main emphasis of the CMSC is the measurement of metabolic parameters using stable isotope tracers and non-labeled metabolic tracers. These include but are not limited to 6,6-D2-Glucose, D5-glycerol, and U-13C-palmitate.
Key to the CMSC is also the quantitative measurement of drugs, drug metabolites and other small molecules by high resolution-accurate mass LC-MS and by triple quadrupole LC-MS. Alternatively, and for the same purposes, the CMSC performs quantitative analysis by GC-MS.
Cryo-Electron Microscopy Core
Jenny E. Hinshaw, Ph.D., Director
Haifeng He, Ph.D., Technical Director
Bertram Canagarajah, Ph.D., Computational Director
The Cryo-Electron Microscopy (CRYOEM) core provides equipment and training in preparing and imaging negative stain and cryo-EM grids. The facility has two transmission electron microscopes, FEI Tecnai T12 and TF20 (equipped with a direct electron detector), which are optimized for negative stain, cryo-EM Single Particle and Tomography imaging. The scopes are in Building 8, room B2A20-24. The facility also has two EM grid plungers, carbon evaporator and glow discharge machines located in building 8, room 1A18.
Automated image acquisition is set up on both scope using the program SerialEM. The data is stored on LCBB, a server located in the Democracy NIDDK IT facility. There is minimal fee for service of the facility. Contact Haifeng He to discuss potential projects and to schedule time on the instruments.
The Genomics Core provides next-generation sequencing (NGS) on a fee-for-service basis to the NIH community, with priority for NIDDK users. Additional resources in support of this technology included consultation services, user-accessible instrumentation, bioinformatics infrastructure, and secure data management.
The facility offers next-generation (massively parallel) sequencing on the Illumina platform (HiSeq 2500 and MiSeq). Users provide libraries to the facility, and submit library information via the sample tracking website. Core personnel assess library quality, perform sequencing, assess data quality, and perform alignment. Data is returned to users by secure FTP. Front-end support includes assistance with experimental design and advice on library preparation. The facility houses a shared instrumentation laboratory and provides training for users. Instruments are available for sample shearing, automated chromatin immunoprecipitation, automated library construction, library quality assessment and purification, and real-time qPCR. Users also have access to integrated software packages for NGS data analysis. Additional bioinformatics support from Core personnel may be available on an ad hoc, collaborative basis.
NIH staff members are encouraged to contact Harold Smith or Chithra Keembiyehetty to discuss the application of facility services to their research programs, or to schedule a visit to the laboratory (located in Building 8, Room 1A11). The Genomics Core Facility was created in January 2003 to provide investigators with innovative, genome-scale technologies in gene expression and DNA sequencing.
For NIDDK Staff Only: Learn how to utilize the Core’s services.
Human Energy and Body Weight Regulation Core
Kong Y. Chen, Ph.D., Director
The Core collaborates with investigators from across the NIDDK, clinical research programs at the NIH, and other institutions by performing metabolic and physiological phenotyping measurements in healthy volunteers as they relate to obesity, physical activity, and energy metabolism, and in patients with metabolic disorders as they relate to specific metabolic dysregulations.
The Core supports the collection of highly sensitive, continuous measurements of whole-body energy metabolism. We use standard bedside indirect calorimetry measurements of resting energy expenditure and whole-room indirect calorimeters (metabolic chambers) over a 24-hour period. We measure sleep, post-prandial, resting, exercise, recovery, and spontaneous movement periods; substrate oxidation rates over 24 hours; physical activity during free living; heart rate and heart-rate variability; and skin and core body temperatures.
The Core also provides standardized measurements of cardio-respiratory fitness (maximum and submaximum tests performed using upright, recumbent, and treadmill) and body composition (collected using dual energy x-ray absorptiometry (DXA), air-displacement plethysmography (BodPod), bioelectrical impedance, and anthropometry). In addition, staff members advise and consult with clinical research teams to optimize measurement selection and protocol design. Finally, Core members coordinate and provide measurement services, perform routine equipment calibrations and maintenance, and manage related data.
Mouse Metabolism Core
Oksana Gavrilova, Ph.D., Director
Mouse models of obesity and diabetes contribute greatly to a better understanding of how environmental and genetic factors affect metabolism. The Mouse Metabolism Core Laboratory supports NIDDK’s intramural investigators by characterizing and analyzing phenotypes of metabolic disease in genetically modified mice.
We analyze the following: body composition (MRI and Echo Medical Systems), body temperature (Mini-Mitter telemetry), activity (Accuscan Open Field), feeding behavior (BioDAQ, Research Diets), energy expenditure (Oxymax CLAMS and Columbus Instruments), glucose metabolism (insulin tolerance, glucose tolerance, first phase insulin secretion tests, and euglycemic-hyperinsulinemic clamps), and lipid metabolism ( triglyceride clearance and production and fatty-acid oxidation in whole animals and in isolated muscle). We also assist in the isolation of pancreatic islets, perform transplantation of islets under the kidney capsule, and measure concentrations of major metabolites and hormones in mouse plasma.
The Biostatistics Program provides advice to extramural and intramural NIDDK staff on the design and feasibility of proposed research studies and the conduct of ongoing studies. Staff in the program:
- perform research on statistical methods,
- conduct educational seminars,
- attend Data and Safety Monitoring Board meetings for extramural project, and
- provide analytical services for intramural research projects.
Laboratory of Animal Sciences Section
Mark B. Foster St. Claire, D.V.M., Director
The Laboratory of Animal Science Section (LASS) provides support and guidance to the NIDDK’s intramural researchers for all phases of laboratory animal experimentation, including:
- advising staff members about practices for the proper housing, handling, care, and use of research animals to ensure compliance with guidelines issued by the HHS, the U.S. Department of Agriculture, and the Association for the Assessment and Accreditation of Laboratory Animal Care;
- managing animal care facilities in order to maximize the use of animals, animal room space, and animal care resources;
- implementing and coordinating animal disease monitoring, investigation, prevention, and treatment;
- providing guidance on animal-study proposal submission; and
- training animal care personnel.
The LASS is responsible for the housing and care of research animals and for enhancing their well-being. The LASS provides technical animal research services to researchers and surgical support. The section’s facilities and services are available to all NIDDK researchers who have been approved to conduct animal research by the Institutional Animal Care and Use Committee.
Metabolic Clinical Research Unit
The Metabolic Clinical Research Unit (MCRU) is a specialized unit located in the NIH Clinical Center. Since 2007, the MCRU has supported clinical research protocols across NIH institutes and collaborations with extramural investigators. Protocols focus on the regulation of human metabolism in healthy volunteers and patients with various metabolic conditions, including obesity, diabetes, liver diseases, rare genetic conditions, neurological disorders, and cancers.
Learn more about the MCRU.
Mouse CRISPR/Cas9 Genome Editing Facility
Richard Proia, Ph.D., Director
The facility supports NIDDK intramural researchers in their efforts to generate genetically modified mice through CRISPR/Cas9 technology.
The facility will superovulate donor mice, harvest single cell embryos and inject CRISPR reagents. Surviving embryos will be implanted into pseudopregnant females. Tail biopsies from the pups will be given to the investigator for genotyping to identify potential founder mice.
NIDDK Central Repository
The NIDDK Central Repository makes data and biospecimens from current and previously-funded NIDDK studies available to the broader scientific community. The Repository enables scientists not involved in the original study to test new hypotheses without any new data or biospecimen collection, and provides the opportunity to pool data across several studies to increase the power of statistical analyses. The NIDDK Central Repository has four major components.
- an archive of clinical data and documentation from NIDDK-sponsored studies
- a collection of biospecimens and an associated database that identifies specimens collected from ongoing and completed studies funded by NIDDK and links them to the associated phenotypic data
- a web portal that contains study-specific information within the Repository and accepts electronic requests for biospecimens and data
- a collection of genotyping data from GWAS and sequencing studies housed at the National Center for Biotechnology Information's (NCBI) database of Genotypes and Phenotypes (dbGaP)
Regulatory Support Program
The NIDDK Regulatory Support Program provides regulatory support for all NIDDK-sponsored trials that require a U.S. or Canadian regulatory application for the use of an investigational drug or device in a clinical trial. Specifically, regulatory consultation is provided to aid in the determination of the need for a regulatory application, protocol development, study drug issues, and other regulatory matters. Regulatory support staff work with the program officials and data coordinating centers (or intramural investigator) to
- initiate regulatory applications,
- maintain applications (e.g., annual reports, protocol amendments),
- assist with safety reporting to FDA and Health Canada, and
- ensure that the Institute is in compliance with any existing or new regulatory requirements.