Approximately 60 core facilities and research centers on the UI campus are supported by the College of Medicine, the Office of the Vice President for Research and/or other center grants (P30s), program project grants (PPGs) and NIH R01 grants awarded to this University. These services and facilities enhance the overall research capabilities of the research community immeasurably by providing access to shared equipment and by maximizing the expertise of researchers in a variety of disciplines. A comprehensive list of core facilities, research centers, and research institutes is available on the Carver College of Medicine web site. These Core Facilities are supported in excess of $3 million annually, by the Office of the Vice President of Research and the Carver College of Medicine. The following is a partial list of the available core facilities, focused on those that are most pertinent to theme of this Center.
Iowa Institute of Human Genetics (IIHG) Genomics Cores and Services
Genomics Division: The Genomics Division provides a broad spectrum of services and resources that include Genome Sequencing (based on next generation sequencing approaches, i.e. NGS), DNA Sequencing (based on the Sanger approach), DNA Microarray, Oligonucleotide, Molecular Biology Computing, and Real-time qPCR services. This laboratory occupies a total of ~2450 square feet of space over six rooms. The director, administrative support, and Oligonucleotide Service occupy a total of ~425 square feet of office space over two rooms. A custom Laboratory Information Management System (LIMS) has been developed that facilitates sample management throughout the workflow. Users receive all information regarding their sample preparations along with their data. All data are backed up and archived. The service has processed samples using NGS technologies for a complete range of applications including: 1) whole genome sequence analysis, 2) RNAseq (quantification of transcripts, i.e., expression analysis), 3) single-cell RNAseq, 4) microRNA discovery and quantification, 5) resequencing, 6) ChIPseq, 7) custom target capture, 8) SNP (variant) detection and discovery studies, and ATACseq.
The IIHG Bioinformatics Division provides the expertise and equipment to carry out the analysis of complex data sets. In collaboration with investigators both on campus and off, the division studies a diverse set of biological questions. Their focus is to derive biological insights from large, complex data sets generated from large RT-PCR, microarray, and NGS experiments.
Comparative Pathology Laboratory (CPL)
The CPL is an animal research support laboratory in the Division of Comparative Pathology of the Department of Pathology in the Carver College of Medicine. The mission of this facility is to provide veterinary pathology services and support to scientists investigating animal models of disease. The CPL serves primarily research faculty within the UI, but also works with outside investigators. This Core also facilitates analysis of blood and urine chemistries for assessing disease in live animals, using both VetScan VS2 and Vitros 530 automated instruments. The Core provides services for the processing, embedding, sectioning, and tinctorial and immunohistochemical staining of tissues. Expertise in the handling of fresh, frozen, and fixed cells and tissues is the building block of the laboratory. The Comparative Pathology Core (Core-4) of this P30, directed by Dr. Katherine Gibson Corley, exists within the CPL.
Office of Animal Resources
The animal resource facilities at UI are extensive. Experimental animals are kept in nine buildings in three distinct geographic locations (East and West sectors of the Main Campus, and the remote Oakdale Campus); ~155,000 square feet are devoted to their care, housing, and related activities. The total cage days of vertebrate animals for the entire University during 2017 was ~9.9 million days. The unit has received full accreditation from the American Association for Accreditation for Laboratory Animal Care (AAALAC). There is a well-established and stringent review procedure for all applications involving animal research at this University, and it meets with the standards set forth by the American Physiological Society. The Medical Education and Research Facility and Bowen Science Building on the main campus, as well as the Transgenic Animal Facility on the Oakdale Campus, contain modern, rigorously-maintained BSL2-Level animal quarters staffed by highly trained technical support personnel. In addition, the UI College of Medicine/Hospitals and Clinics is among few medical centers in the United States that have an authorized program for utilizing hospital equipment to perform animal studies. Animal studies have been performed in the Ultrafast Computed Tomography (CT) Facility, the Nuclear Magnetic Resonance Imaging Facility and the Positron Emission Tomography Imaging Center. All aspects of the animal care program at UI are superb, and it has been an enormous asset to investigators performing research requiring experimental animals of various species.
Biomedical Research Store
Located on the second floor of the Eckstein Medical Research Building, the 2,500 square-foot Biomedical Research Store provides UI researchers easy procurement of common molecular and cell biology enzymes, reagents and kits. The molecular biology reagents include, but are not limited to, restriction and other DNA modifying enzymes, DNA and RNA purification kits, competent cells, quantitative (“real-time”) PCR chemistries and consumables, and nucleotides. Tissue-culture reagents include, but are not limited to, antibiotics/antimycotics, dissociation enzymes, growth factors, media, media supplements, salt solutions, serums, transfection reagents, and endotoxin-free water. Large-volume contracts enable the store to negotiate low prices, as well as to eliminate shipping and packaging fees. Products are available at walk-up windows located on the second floor of the Eckstein Medical Research Building. This service provides investigators with convenient and rapid access to small quantities of enzymes, in many cases eliminating the need for individual laboratories to maintain expensive inventories.
Small Animal Imaging Core
The Small Animal Imaging Core (SAIC) is a core facility of the Iowa Institute for Biomedical Imaging (IIBI) and the Holden Comprehensive Cancer Center (HCCC). The purpose of SAIC is to provide a comprehensive service for non-invasive anatomical and physiological imaging of small animals (mice, rats, ferrets, etc.) and other biological tissue samples. Core instrumentation consists of several imaging modalities that have been specifically purchased or modified for scanning small animals. Imaging services include microPET imaging, gamma camera scintigraphy, whole tissue biodistribution assays and autoradiography using positron emission tomography-computed tomography (PET/CT), and single-photon emission computed tomography (SPECT/CT). The SAIC staff assists investigators with defining which one or more of the imaging modalities are appropriate for their research needs. This assistance encompasses the choice of the most appropriate radiopharmaceutical and imaging methodology to capture the physiological process of interest. The Core works with investigators to develop a timetable for experiments, determines the numbers of animals required to demonstrate feasibility and/or significance, and assists the research team with the development of imaging sequences and image analysis schemes. The Core has the capability to serially image awake and anesthetized animals. The staff will also assist with collaborations between HCCC investigators and other experts across the UI campus to facilitate the investigation of new radiopharmaceuticals, contrast media, drugs, therapeutic interventions, or other specialized techniques that may be necessary for specific experiments. For PET imaging, the radiopharmaceuticals that are currently available are FDG ([18F]fluorodeoxyglucose), FLT ([18F]fluorothymidine), acetate ([11C]acetate), choline ([11C]choline) and others. FDG is routinely available on a daily basis. All other available PET radiotracers require schedule coordination with radiochemistry staff. If PET radiotracers other than those listed above are desired, Dr. Timothy Tewson is consulted on the potential availability and cost.
Flow Cytometry Facility
The 1,200 square-foot Flow Cytometry Facility is located in the Eckstein Medical Research Building (EMRB). The Facility has one magnetic-based and ten laser-based instruments whose major purpose is the identification and isolation of various cell populations, and the quantification of hormones and cytokines. The specific instruments in the Core include: Becton Dickinson Aria II, Becton Dickinson FACS DiVa, Becton Dickinson LSR II with 355nm, 488nm, and 633nm lasers, Becton Dickinson LSR II with 405nm, 488nm, 561nm, and 639nm lasers, Becton Dickinson LSR II (VA satellite lab) with 405nm, 488nm, and 633nm lasers, Becton Dickinson FACS Calibur, Becton Dickinson FACScan, BioRad BioPlex, Miltenyi autoMACS. The Facility provides scientific and technical personnel who are available for consultation in designing experimental protocols and training in the use of bench-top instruments and software programs for the interpretation and analysis of data. Cell preparation protocols and publication-quality output are available upon request. Data analysis using FlowJoTM, CellquestTM, and ModFITTM can also be performed offline at investigator laboratories or offices using the Facility's system of networked computers, which can be accessed via its dedicated file server. Data are archived on a separate server and stored for at least ten years. This core is used for hormone analysis in this grant.
Viral Vector Core
The overall objective of the Viral Vector Core is to support investigators in the use of gene transfer technologies. This Core utilizes molecular biology techniques to engineer and develop viral vectors based on multiple vector systems necessary for gene transfer in research experiments or pre-clinical studies. Core staff and investigators work together, allowing for cross-fertilization of ideas, technical advancements, and innovations in vector design. The Core brings investigators who are interested in developing and using viral and non-viral vectors for gene transfer together with specialists in the area of vector construction, by: 1) consulting with the Principal Investigator to plan and develop transfer vectors that fit individual project requirements, 2) assisting investigators with troubleshooting for existing projects, 3) designing and developing novel vectors, 4) developing novel methods of virus production such as the RapAd™ System for adenovirus production, 5) generating RNAi expression vectors, 6) constructing, amplifying, purifying, concentrating, and performing quality control on preparations of recombinant adenovirus, adeno-associated virus (AAV), Moloney murine retrovirus, lentivirus, recombinant vaccinia virus, and baculovirus; 7) helper-dependent Adenovirus (i.e., gutted with no viral genes), and 8) maintaining and distributing recombinant reporter viruses. The Vector Core is located in this facility.
Genome Editing Facility
The Mouse Genome Editing Facility provides centralized instrumentation and expertise for the generation, breeding and analysis of both transgenic and gene-targeted animals. The facility is comprised of four personnel trained in a variety of mouse embryo manipulations for producing genome-engineered mice. This includes transgenesis and CRISPR/Cas9 HDR approaches using pronuclear microinjection. Additional services include the design and validation of transgenic constructs and CRISPR/Cas9 reagents, screening of founder animals, genotyping of mouse colonies, and backcrossing of strains. The facility also provides services and storage for embryo and sperm cryopreservation, as well embryo and mouse re-derivation and in vitro fertilization of cryopreserved sperm. The facility evaluates and expands mouse embryonic stem cells, and injects them into blastocysts. It maintains all animals in strict specific pathogen free (SPF) barrier conditions and has three wet laboratories, a microscopy suite, a tissue culture room, and a molecular biology laboratory. The facility currently has a 100% founder success rate, with nearly 300 different constructs.
The Proteomics Facility, located on the third floor of Eckstein Medical Research Building, provides services and state-of-the-art instrumentation for discovery proteomics or more in-depth quantification studies. Services currently available in the Facility include: molecular weight determination of intact proteins and macromolecules, small molecule structural and quantitative analyses, protein identification following proteolysis in polyacrylamide gels or solution, applying MASCOT, SEQUEST or SpectrumMill search engines, as well as characterization of certain post-translational modifications. Equipment in the Facility includes a Bruker UltrafleXtreme MALDI TOF/TOF, a Thermo LTQ XL linear ion trap with electron transfer dissociation capabilities and an atmospheric MALDI source, an Agilent 6520 quadrupole time-of-flight (Q/TOF) with routine 10 ppm mass accuracy, an Agilent 6400 triple quadrupole (3Q) for tandem MS/MS scanning, especially multiple reaction monitoring. The Agilent instruments are interfaced to state-of-the-art, ChipCube platforms driven by Agilent 1200 nano- and capillary HPLC pumps. Matched Dionex 3000 RSLC two dimensional capillary systems are interfaced to an Proteineer II robotic fraction collector (for off-line separation prior to MALDI MS/MS) and the Linear Trap Quadrupole. The matched liquid chromatograms for ESI and MALDI are used to build accurate mass and retention time libraries for tissue archives. Associated equipment includes a Dionex ICS 3000 for glycoproteins or chromatofocusing, an automated digester, electrophoresis units, an OffGel Fractionator and an Eksigent 2D nanoLC to partition complex peptide mixtures using isoelectric focusing or strong cation exchange (SCX) chromatography.
The Bioengineering Facility maintains two units for the design of new equipment and the maintenance of research or other electronic equipment. The design unit offers custom electronic design and fabrication services. Capabilities include embedded micro-controllers, digital signal processing, custom programmable logic devices, computer interface, and high-performance analog amplification and signal conditioning. The maintenance section repairs electronic equipment and schedules regular maintenance inspections.
Central Microscopy Research Facility
The Central Microscopy Research Facility (CMRF) provides instrumentation and technical assistance to research programs involving the use of scanning and transmission electron microscopy, light microscopy and confocal microscopy, freeze fracture and x-ray microanalysis. The CMRF provides all solutions, supplies and training necessary for investigators involving microtomy, including specialized staining and embedding techniques, negative staining, metal coating, immuno-cytochemistry, morphometry and stereology, the preparation of material samples for both transmission and scanning electron microscopy, including x-ray microanalysis and other procedures. Basic equipment includes: Olympus BX-51 and Nikon Optiphot light microscopes equipped for brightfield, darkfield, and phase, Hitachi scanning electron microscopes, and JEOL and Hitachi transmission electron microscopes. The facility has a Bio-Rad Radiance 2100MP multiphoton/confocal microscope, a Bio-Rad MRC-1024 confocal microscope and several Zeiss 510 confocal microscopes. The facility has Kratos Axis Ultra X-Ray photoelectron spectroscopy system, VEECO/DI Multimode IV Scanning Probe microscope and Asylum Research atomic force microscope. The facility has a Xenogen IVIS 200 system that allows researchers to use real-time imaging to monitor and record cellular and genetic activity within a living organism. Additional equipment includes a Balzers HPM-101 high-pressure freezer, a Balzers 301 freeze fracture system, a Leica cryosubstitution unit, Reichert and Leica ultramicrotomes and a digital darkroom/image editing workstation. Microscopy courses and workshops by staff are regularly offered free of charge. The CMRF recently installed a Stimulated emission depletion (STED) microscope for ultra-high-resolution microscopy.
Protein and Crystallography Facility
The Protein and Crystallography Facility provides all support and infrastructure necessary for initiating and completing protein purification, biophysical characterization and structural studies. This includes three BioRad DuoFlow FPLCs for protein purification, a Wyatt NanoStar dynamic and static light scattering instrument for aggregation and protein size determination, a ForteBio Octet RED96 biolayer interferometry system for protein:protein and protein:DNA binding studies, a thermal shift assay workflow to identify protein stabilization conditions using a BioRad CFX96 qPCR instrument, a TTP LabTech Mosquito nano-volume robot for arraying multiple crystallization conditions, a Formulatrix RockImager2 for imaging crystal trays, and a TTP LabTech Dragonfly liquid-handling robot for preparation of custom solution arrays. Diffraction data can be collected locally using two R-AXIS IV++ systems mounted on rotating anode generators or by shipping to our 4.2.2 Molecular Biology Consortium beam line at the Advanced Light Source (Lawrence Berkeley National Laboratory), where data collection is performed remotely from Iowa. The facility also enables analysis by small-angle X-ray scattering (SAXS) in line with size exclusion chromatography (SEC) and multi-angle light scattering (MALS). Data are routinely collected in person from the 18-ID-D Bio-CAT beam line at the Advanced Photon Source (Argonne National Laboratory), or via a mail-in system from the 12.3.1 SIBYLS beam line at ALS. The facility is also set up with several workstations and an SBGrid Consortium membership, which provides updated versions of all necessary structural biology and molecular modeling software.
Electron Spin Resonance Facility
The Electron Spin Resonance Facility provides expertise and instrumentation to pursue research questions dealing with oxygen free radicals, singlet oxygen, nitric oxide, and the array of related oxidants and antioxidants that influence the overall redox environment of cells, tissues, and whole organisms. The facility houses two Bruker EMX ESR Spectrometers and an Varian E-4 ESR.
High Throughput Screening Facility
The University of Iowa High Throughput Screening Facility (UIHTS) provides a high-throughput platform that integrates robotics, detection systems, and chemical/biologic libraries to enable highly flexible screening services, project management, grant assistance, and assay/technology development for UI investigators. Instrumentation systems allow for scalable screening toward drug discovery and development, including the screening of large chemical/biologic libraries. This facility also enables molecular probe discovery for mechanism-of-action studies by screening focused and intellectually designed compound collections. The UIHTS is equipped to perform high-throughput screening in 96-, 384-, and 1536-well formats with plate reader detection (Perkin-Elmer EnVision), using absorbance, fluorescence, and luminescence (including advanced FRET and BRET techniques). UIHTS is also equipped to perform high-content screening (HCS, Perkin Elmer Operetta Confocal Imaging System) based on the detection and quantification of: phenotypic changes, i.e., cell differentiation, cell migration, neurite outgrowth, and target trafficking; changes in the fluorescence intensities of target proteins, including transcription factors; or signaling pathway activity. HTS and HCS systems are integrated with robotics systems for plate handling and assay execution and are suitable for small- or large-scale compound library screens that are fully automated. UIHTS holds both small-molecule drug libraries and biological libraries. Currently, the small-molecule libraries include: 1) a drug library that contains 1,018 FDA-approved compounds and is used primarily to identify drugs that can be repurposed; 2) a pathway- or target-selective collection (PTSC) containing 1,310 compounds for mechanism interrogation; 3) the Spectrum Library from MicroSource (MSSP), which contains 2,320 structurally diverse compounds, including marketed and experimental drugs as well as natural products (this is typically the starting point for pilot screens); 4) the ChemBridge Diverset, a collection of 50,000 small molecules that represent a wide swath of chemical space and are optimized to be “drug like” considering factors such as partition coefficient and Lipinski-like rules; 5) the Maybridge Ro3 Diversity Fragment Library, which contains 1,000 fragments that were carefully selected to optimize the balance between broad coverage of lead-like diversity space and the number of fragments; 6) the NIH NCI NExT collection of 83,536 small molecules, a general screening set that was designed to identify lead compounds for drug discovery projects and that is comprised of three non-separable subsets of the Legacy molecular library small molecule repository (MLSMR), 15 privileged scaffolds in two Diversity subsets. Biological libraries cover the cell collections of melanoma cell lines and breast cancer cell lines, and arrayed Kinome-wide CRISPR gRNA library from Integrated DNA Technologies.
University of Iowa Clinical and Translational Science
Approved by the Iowa Board of Regents in December 2006, the Institute for Clinical and Translational Science (ICTS) is the epicenter of clinical and translational science at UI and serves as the academic home for the clinical and translational research and training conducted here. It provides an area of great opportunity and future growth for clinical and translational researchers. The ICTS's unique overarching academic structure provides a multidisciplinary matrix for facilitating and supporting clinical and translational science throughout the UI colleges as well as the UI Hospitals and Clinics. ICTS functions include:
- Stimulating new interdisciplinary clinical research programs to consolidate and improve the UI research infrastructure.
- Training highly motivated clinical research scholars for innovative careers in patient-focused research.
- Providing a useful and integrated foundation for data and knowledge management capable of supporting the advancement of clinical and translational research on a grand scale.
- Provide engaging community programming driven by the principles of community-based participatory research.
- Strengthening the UI research infrastructure.