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Research

Research Cores/Resources

The Research Cores and Research Resources provide access to state-of-the art, specialized equipment and related expertise to support the research activities of investigators throughout the University of Notre Dame and beyond. Such facilities also enhance the education of undergraduate students, graduate students, and postdoctoral fellows. By expanding the base of sponsored research and providing a strong research infrastructure, these cores and resources promote collaborative research among investigators within the institution and with other scientists throughout the country.

The list below represents the current offerings from several colleges on the Notre Dame campus. We hope to expand the list and provide more University-wide facilities to enhance research collaboration opportunities.

Research Cores (Re-Charge Centers)

The research cores listed here are all available for use by University investigators (and in some cases, external customers). Use of these cores should be coordinated through the contact person listed with each core description.

Bioinformatics Core

The Bioinformatics Core at the University of Notre Dame provides consulting, access, and assistance for common genomics/bioinformatics analyses. Most of our current consulting portfolio centers on data produced by our sister Genomics Core, including traditional and “next-gen” sequencing applications, microarray analysis, phylogenetics, and other genomics-focused informatics. The core also provides access to significant storage and computing resources for its users. Individuals in need of these or customized solutions to their bioinformatics needs should contact Scott Emrich (574-631-0353; semrich@nd.edu) for more information, or visit nd.edu/~biocmp/core.

The Center for Nuclear Magnetic Resonance Spectroscopy

The Center for Nuclear Magnetic Resonance (NMR) Spectroscopy at the University of Notre Dame supports new and ongoing research in chemistry, chemical engineering, biochemistry, molecular biology, and related fields. Our instrumentation enables us to perform state-of-the-art multinuclear, multidimensional, high-resolution NMR experiments at various field strengths and temperatures to determine the molecular structures and dynamics of a wide range of compounds (e.g., proteins, nucleic acids, carbohydrates, synthetic polymers, natural products, lipids, and macrocyclic polyethers).

For more information on the Center for NMR Spectroscopy, please contact Jaroslav Zajicek, Ph.D., at 574-631-9111 or jzajicek@nd.edu.

Center for Zebrafish Research

The Center for Zebrafish Research (CZR) at the University of Notre Dame is housed in approximately 3,000 square feet in the Galvin Life Science building. The CZR consists of eight double-sided racks and 38 single-sided racks that allow for a flexible arrangement of tanks from 1.5 to 8 liters in size. Racks are maintained on multiple, independent life-support systems to minimize a catastrophic event to the entire system. A separate room houses the zebrafish nursery. The approximate total capacity of the CZR is 120,000 adult zebrafish (one of the largest systems in the Midwest).

The CZR provides several services including the generation of ENU-induced mutants and screening of mutant phenotypes, the introduction of morpholinos into embryos and some adult tissues to assay for loss-of-function phenotypes of specific target proteins, and microinjection of DNA constructs and subsequent analysis of transgenic lines.

For more information, contact David Hyde, Ph.D., at 574-631-8054 or dhyde@nd.edu.

The Freimann Life Science Center

The Freimann Life Science Center (FLSC) at the University of Notre Dame is a state-of-the-art animal research facility with 30,000 square feet of flexible use space. The FLSC is fully accredited and registered, and has a highly trained, certified, professional staff available to assist with surgical and other technical procedures.

The FLSC has individually ventilated caging for rodents and the capability for housing non-human primates It is home to the Lobund-Wistar rat model of metastasizing prostate cancer.

For more information on the FLSC, contact Dr. Mark Suckow at 574-631-6085 or suckow.1@nd.edu

Genomics Core

The Genomics Core has an ABI 3730 sequencer for generating DNA sequence reads using the classical Sanger method. A Roche 454 Genome Sequencer system has recently been purchased and will be available as service in spring 2009.

The facility operates three microarray platforms for analysis of transcripts from various tissue types and gDNA genetyping and comparative genome hybridization. These include the Affymetrix GeneChip system, "print your own array," and the Nimblgen Hybridization system and the Gene Pix scanner.

Real time quantitative pcr (TaqMan) technology is available in the facility for q-pcr and a range of DNA and RNA-based quantification experiments.

The Genomics Core at the University of Notre Dame can accommodate a range of sequencing and expression analyses. Please contact the faculty director, Dr. John Tan, at 574-631-1902 or Tan.14@nd.edu for more information.

Mass Spectrometry and Proteomics Facility

The University of Notre Dame Mass Spectrometry (MS) Facility provides instrumentation and expertise for the analyses of compounds ranging from small organic molecules to large biomolecules with applications in the areas of metabolomics, proteomics, and lipidomics. In early 2009, an expanded and upgraded facility will relocate to newly renovated space in Stepan Hall of Chemistry and Biochemistry.

Available instruments include a Bruker Autoflex III MALDI-TOF-TOF, Bruker MicrO-TOF II time-of-flight (TOF), Bruker MicrO-TOF QII quadrupole time-of-flight (Q-TOF), Micromass QuattroLC triple quadrupole, and JEOL AX505HA and GCMate magnetic sector mass spectrometers. A Bruker HCT Ultra ion trap equipped with electron transfer dissociation and interfaced with a Dionex Ultimate 3000 2DLC system will be available in mid-2009. These instruments include ionization methods such as EI, CI, FAB, ESI, nanoESI, and MALDI. Analyses include low resolution MS and MS/MS, high resolution MS and MS/MS, and accurate mass measurements. Hyphenated techniques include GC/MS, LC/MS, and LC/MS/MS via capillary GC, HPLC, capillary HPLC, and ultrahigh pressure LC systems. Proteomics applications (post-translational modifications, peptide mass fingerprinting, in-gel, and in-solution protein digests), metabolomics studies (LC/MS and LC/MS/MS), and imaging MS (TLC separations and tissue sections) experiments via MALDI-TOF and MALDI-TOF-TOF are also possible.

For more information on the MS Facility, please contact William Boggess, Ph.D., at 574-631-4027 or wboggess@nd.edu, or visit the website at nd.edu/~massspec.

The Notre Dame Integrated Imaging Facility

The Notre Dame Integrated Imaging Facility (NDIIF) is a new state-of-the-art research core that houses and integrates three areas of Notre Dame imaging expertise: electron microscopy, optical microscopy, and small animal imaging.

In addition, the NDIIF supports an interactive network of research groups, who are connected by their interest in imaging technology, and allow them to cross-fertilize ideas and form interdisciplinary collaborations. The NDIIF makes available an integrated suite of sophisticated microscopes and imaging stations that enable the expert users to attack the most complex modern research problems and, equally important, the resident professional staff (technicians and research specialists) to guide non-expert users and allow them to conduct experiments that were previously beyond their limits. Below is a list of capabilities and contacts for early 2009. To see updates, please visit nd.edu/~ndiif.

Electron Microscopy:
  • Field Emission Scanning Electron Microscope
  • Dual Source Focused Ion Beam
  • Transmission Electron Microscope (end of 2009)

Contact Alexander Mukasyan, Ph.D., research professor, at 574-631-9825 or amoukasi@nd.edu.

Optical Microscopy
  • Deconvolution Optical Microscope
  • Spinning Disk Confocal Microscope with TIRF
  • Laser Scanning Confocal Microscope
  • Two-Photon Laser Scanning Confocal Microscope (End of 2009)

Contact Dr. Richard Sorrentino at 574-631-1627, or at Sorrentino.5@nd.edu.

Animal Imaging:
  • Optical Animal Imaging, Fluorescence, Bioluminescence
  • Planar X-Ray Imaging
  • Micro-CT X-Ray Animal Imaging Station

Contact W. Matthew Leevy, Ph.D., research assistant professor, at 574-631-1683 or mleevy@nd.edu.

X-Ray Diffraction Facility

The X-Ray Diffraction (XRD) Facility at the University of Notre Dame provides for X-Ray structural studies of small (ca. 2kDa) molecules. XRD has the capability to examine a wide range of molecules from “light atom” biologically relevant to metal-complexed compounds that can be readily analyzed using nondestructive techniques.

Applications of these techniques include molecular and atomic identification (can differentiate atom types), molecular interactions (solid state), electrostatic interactions, and Van der Waals interactions. XRD provides an accurate starting point for molecular simulation (computational) studies and stereochemical analysis is essential for understanding bioactive molecules.

The facility houses three instruments: two of which produce molybdenum wavelength radiation, and one of which produces copper radiation. Copper radiation is ideal for stereochemical analysis of light atom structures. All of the instruments utilize area detector format readout and allow for a high-throughput of samples.

For more information on the XRD Facility, please contact Allen Oliver, Ph.D., at 574-631-5935 or aoliver2@nd.edu.

Research Resources

The research resources listed here are all available in the Keck Center for Transgene Research. Use of these resources should be coordinated through the assistant director, Mary Prorok, Ph.D., who can be reached at 574-631-9120 or mprorok@nd.edu

Analytical Ultracentrifuge (Beckman XL-I)

The reversible self-association of proteins, lipids, carbohydrates, and nucleic acids is a frequently encountered phenomenon in the biological realm, but the characterization of such events can be difficult. Using analytical ultracentrifugation (AUC), the sedimentation equilibrium behavior of such biomolecules can be examined to address the existence of dimeric and/or higher order multimers in a variety of solution conditions. This methodology draws on the fact that the equilibrium distribution of an analyte in a centrifugal field is related to its buoyant molecular weight. In our instrument, the gradient of analyte can be assessed by either absorbance optics (200–800 nm) or interferometry. Any biomolecule of mass greater than 200 Da can be examined by this method. AUC can also be performed in sedimentation velocity mode. In this case, the speed at which an analyte sediments in a centrifugal field can provide an estimate of the, size, shape, and homogeneity of the species. Sedimentation is particularly useful for determining if a change in the conformation of the macromolecule (as reflected by a change in its hydrodynamic volume) attends ligand binding.

Cell Culture Core

Gene-altered mice are a valuable resource. Cell cultures obtained from these altered mice may be invaluable in many studies. The Cell Culture Core of the Keck Center has mastered techniques to isolate pure populations of a variety of primary cell cultures. Among the cell types that can be isolated are mouse aortic and colonic endothelial cells, and splenic and bone marrow dendritic cells. These cells can be obtained from wild-type and/or gene-altered mice.

Circular Dichroism (CD) Spectrometer (Aviv 202 SF)

CD spectroscopy exploits the chiral nature of biological macromolecules and is grounded in the precept that chiral species interact differently with left- and right-circularly polarized light. The method is most frequently applied for assessing the secondary structure of proteins and peptides. A simple wavelength scan of a solution of the protein or peptide in the far ultraviolet range (195–≠240 nm), followed by software-assisted deconvolution of the resultant spectrum, can provide an estimate of the fractional conformer content, including alpha-helix, beta-sheet, beta-turn, and random coil contributions. The sample compartment can access temperatures ranging from 5 °C to 95 °C, a feature that can be used to generate melting curves at select wavelengths. The instrument is also equipped with a stopped-flow mixing module that can permit investigation of protein folding events that occur on timescales of 5 ms or longer.

Fermentation

The Keck Center has two BioFlo 3000 benchtop bioreactors for conducting yeast fermentation. Yeast expression systems offer unique capabilities for protein production. Large quantities of protein can be produced in a very simple media.

The simplicity of the media, having one carbon and one nitrogen source, allows for total labeling of the protein with stable isotopes. This is especially useful for NMR and other protein characterization studies.

Laser Capture Microdissection (LCM)

LCM allows for the isolation and purification of single-cell tissue populations. A laser is focused through a microscope to capture specific areas of tissue, specific organs, or specific cells. The tissue samples can then be used for RNA preparations for gene analysis or other analyses. An Arcturus PixCell II system and a Veritas system are in place.

The Keck Center has used this technique to capture normal, adenoma, and carcinoma samples from the same murine subject. This method has provided very pure populations of cells for analysis.

Mouse Strains with Altered Hemostatic Genes

The Keck Center has the largest repository of mice with alterations of hemostatic genes in the world (see attached list). Keck Center personnel are well versed in the varying phenotypes of these mice and are willing to work with other investigators who may find these gene-altered mice valuable for their research. Some mice in the inventory may be freely shared; others may require permissions from other investigators.

Veterinary Ultrasound

Mice are anesthetized using isoflurane, and imaged using ultrasound technology by VisualSonics (Vevo 770). Contrast agents can also be utilized for increased visualization of specific organs and other structures.

The Keck Center has successfully used ultrasound to visualize tumor growth, neovascularization, monitor pregnancy, assess atherosclerotic plaque build-up, etc. in murine models.

Veterinary Endoscope

Mice are anesthetized using isoflurane, and the Storz endoscope is inserted for visualization of the intestinal track. Various tips are available for use on the endoscope, which allow for injecting various reagents, measuring tissue mass, tissue collection, and polyp removal.

The Keck Center has used this instrument for counting the number of masses, polyp removal and subsequent tissue analyses, and overall intestinal health observations.

Whole Animal Lung Resistance

Lung hyper-responsiveness can be measured using the plethysmograph (Buxco). Whole body chambers allow the mice to move about freely. An aerosol delivery system introduces irritants for challenge conditions.

The Keck Center has used this equipment to study asthma/lung inflammation in wild-type and gene-altered mice.