esources: Core Facilities  
 

The Bioinformatics Program has labs and offices in the NMR Dockside Building. Computational and Oracle relational database management systems are served via a Sun Microsystems SunFire 4800 server with eight UltraSPARC III 900 MHz CPU and 16 GB of RAM running the Solaris 8 unix operatating system. We use Splus6 as our compute and statistics engine and Oracle 9i as our  RDBMS. Web content is served via Apache as is our locally written graphical user interface (GUI) to the RDBMS and the web-based analytical toolkit. For graphically and computationally intensive jobs, we have a Silicon Graphics Inc. (SGI) Octane2 Unix workstation having dual 400 MHz R12K processors with 5 GB RAM and a SGI Indigo2 R4400 Unix workstation with 1 GB RAM. Less intensive and secondary data processing is performed on our four Dell dual 1700 MHz CPU Windows2K workstations with 1GB RAM each. Each of the Unix and PC workstations can be used as a front-end for the Sunfire 4800 server.  
 

A strength is the ability to write custom analytical and display software to handle computationally intensive analyses and provide sophisticated graphical displays for our users. Director Dr. Bruce Luxon has 30 years’ experience writing scientific software and can direct our highly trained staff in the creation of virtually any software tool we may require. To facilitate lower order data processing and to enable UTMB’s bioMedical researchers to have more and better access to data analysis tools in their own labs, UTMB has an unlimited site license for Sporfire’s DecisionSite® software, a premium web-based microarray analysis and data mining suite that runs on Pcs. Spotfire allows graphical, 2 and 3D visualization of microarray data, statistical analysis, and a suite of data query devices.  
 

The Biomolecular Resource Facility (BRF), A. Kurosky, Director, is a UTMB-designated core facility providing research support targeted to the analysis of biomolecules, especially proteins and peptides. Originated in 1975, the facility has grown considerably to meet the analytical needs of UTMB investigators. The BRF is composed of 7 core laboratories whose services are briefly outlined below. A more complete description of BRF services can be found at www.utmb.edu/brf.  The BRF overarching philosophy is to provide, at reasonable cost, bioMedical researchers with a relevant menu of analytical services that will enhance their funded research projects and the quality of their publications. Importantly, the BRF puts considerable effort into obtaining major state-of-the-art instrumentation too expensive for individual investigators. Researchers are encouraged to interact closely with BRF personnel to obtain maximum benefit of services. User fees are minimal, compared with other institutions, largely due to support from several UTMB centers, e.g. NHLBI Proteomics Center, NIEHS Center, and the Sealy Center for Environmental Health and Medicine. The BRF occupies 6,200 square feet, distributed among 12 laboratories and 7 offices in the Basic Science Building.  The current scientific staff includes 18 individuals (9 PhD, 3 MS, 6 BS). 

 

Biosynthesis & Biomarker Core – Services include a) biosynthesis of recombinant proteins in bacteria or yeast cultures; b) protein purification and characterization; c) polyclonal antibody production, and d) SELDI biomarker analysis.

Mass Spectrometry Core - Services are a) MALDI – TOF/TOF MS/MS analysis; b) electrospray ionization MS/MS analysis, including liquid chromatography (LC/MS/MS); c) peptide mass fingerprint analysis; d) post-translational modification identifications, and e) stable isotope methods (e.g. iTRAQ and ¹⁸ O).

Peptide Synthesis Core - Offers a) FMOC automated solid phase synthesis; b) peptide purification, and c) peptide mass analysis

Protein Chemistry Core - Provides a) DNA sequencing; b) protein sequencing; c) amino acid analysis, and d) carbohydrate analysis.

Proteomics Bioinformatics Core – Provides a) nonlinear 2D gel analysis; b) Genologics LIMS for data/sample management and access, and c) database searching.

Separations Technology Core – Provides a) HPLC analysis; b) 1D and 2D gel electrophoreses; c) fluorescence gel staining and imaging, and d) robotic gel spot picking and processing for MS analysis. 
 

The Office of Biostatistics (OBIOS) provides statistical support services to all faculty, staff and students at UTMB, including producing power calculations, determining sample size, designing studies that minimize the effects of measurement and experimental error, and identifying appropriate methods for data collection summary and analysis. OBIOS uses the computer package SAS^®, a statistical application with extensive data management capabilities. The Computing Services Center maintains an IBM 3090 500J Mainframe computer. It supports 2 Telex 3420 tape drives and 12 3480 IBM cartridge drives. The CPU has 512 megabytes of memory and 200 giga bytes of direct access storage devices. The system supports MVS/ESA, the ROSOOE editor, SAS, VSAM/DBMS, IM/DBMS, and ADABAS/DBMS. The center has an SNA network and supports TCIP devices which support access to INTERNET and BITNET, and Ethernet.  
 

In collaboration with the Moody Medical Library, OBIOS also maintains a repository of public data files and their documentation, including U.S. Bureau of Census data and National Center for Health Statistics surveys. OBIOS also offers students assistance in the analysis of these data and other complex sample surveys.  
 

The Environmental Exposure Facility provides state-of-the-art capabilities for conducting exposures of experimental animals and in vitro models to gas phase environmental toxicants.  A service core of the UTMB Sealy Center for Environmental Health and Medicine, it supports all UTMB investigators and students on a fee-for-service basis.  In addition, the facility provides a foundation for inter-institution collaborative investigations.  The facility is housed in an 800 square foot, three-room suite. In addition to a room for exposure chambers, an animal housing room and a room for conducting in-vitro exposure of cells in culture make up the facility. Four 0.8 M³ stainless steel Hinnars-type exposure chambers are available for exposure of small laboratory animals to low concentrations of gas phase chemicals. The facility is equipped for studies using organic chemical vapors, ozone or nitrogen dioxide. The chambers receive filtered, air-conditioned, building air at a rate of 30 chamber changes per hour. Regulation of gas concentration is accomplished using mass flow controllers. Organic vapor concentrations are monitored by gas chromatography. Concentrations of ozone or nitrogen dioxide are determined by dedicated gas monitors. The suite is maintained under negative pressure relative to the surrounding building spaces to insure that any exchange of air is from the building into the facility, which also has safety interlocks that shut down gas and air flow in the event of a power interruption or if a smoke detector is triggered. The in vitro exposure facility uses similar equipment to deliver gases to small glass chambers placed on tilt tables in cell culture incubators. 
 

The Flow Cytometry Core Facility in the Department of Microbiology and Immunology aids and advises investigators in the application of flow cytometric techniques to their research. The facility contains three instruments that enable investigators to perform standard procedures in flow cytometry, from phenotypic/functional analysis of cells to cell sorting, and offer room to develop new techniques. The Becton-Dickinson FACS Aria is available for cell sorting. Two analytical flow cytometers (a Becton-Dickinson FACS Scan, and FACS Canto) are available for non-preparative work. These three instruments The FACS Scan is capable of up to three-color analysis. The FACS Canto can provide up to six-color analysis, and the FACS Aria is capable of nine-color analysis in its present configuration, in addition to cell sorting functionality. The core lab can assist with protocol development and implementation, as well as data analysis. The data from all of the core lab cytometers is available campus-wide over the university's broad-band network, such that investigators may analyze and store data in their own labs.  
 

The General Clinical Research Center (GCRC) is one of the first of approximately 80 centers in the nation currently supported by a grant from the National Center for Research Resources General Clinical Research Centers Program of the National Institutes of Health, and separately by the University of Texas Medical Branch.  A broad spectrum of biomedical research is conducted there by investigators funded by internal and external research grants. The GCRC inhabits recently renovated space on the fifth floor of John Sealy Hospital, easily accessible to investigators and research subjects.  The new GCRC has expanded inpatient and outpatient rooms, administrative offices, metabolic kitchen, sleep laboratory, core laboratory, special procedures, support rooms, a telemedicine room, expanded bioinformatics core offices, private dining and waiting rooms, and a large conference room for GCRC staff meetings and clinical research education.  
 

The Core Laboratory and Imaging Core in the GCRC facilitate processing and analysis of blood and tissue samples and assist with those aspects of experimental design that deal with acquiring laboratory data and their interpretation.  
 

The GCRC Imaging Core facilitates investigator's research that requires imaging and body composition measurements. Nutrition and metabolic studies often utilize DEXA for the determination of lean body mass and bone mineral density. A large number of current projects require multiple DEXA measures each for the determination of lean body mass in conjunction with nutritional and metabolic interventions. The simultaneous acquisition of lean body mass and bone mineral density further enhances the analytical value of DEXA.  
 

The total body gamma counter is a unique instrument that affords us the capability of determining lean body mass in populations with altered fluid compartmentalization. Currently the instrument is tuned to count the natural gamma emissions of 40K from the body, which we presently call the total body potassium counter (TBK).  This methodology is particularly useful in study populations where body fluid compartmentalization is altered by trauma or pharmacology. For example, burn injury results in a dramatic loss of intravascular fluid and tissue edema. Compartmental fluid balance is often not restored until the patient is near discharge; one of the shortcomings of DEXA in these situations is that abnormally increased extracellular water will distort the usual relationship between fat-free mass and cellular mass (some may be in the vascular space) is often erroneously measured as lean body mass. In this respect, TBK provides a rapid, reliable, and non-invasive method for quantifying lean body mass changes in these populations.  
 

Magnetic resonance imaging has been used by many GCRC investigators to determine muscle volume and fat changes associated with long-term interventions. Lower body imaging is employed to study leg muscle and fat changes associated with inactivity, the use of anabolic agents in aging, and pediatric and adult burn rehabilitation.  
 

Infectious Disease and Toxicology Optical Imaging Core (OIC) assists with high-resolution imaging and analysis of specimens, including those exposed to infectious agents and/or treated with toxic substances. Agents with infectivity can be accepted up to biosafety level 2, and fixed specimens lacking infectivity will be accepted for any infectious agent authorized on the UTMB campus. The OIC is equipped with a Zeiss LSM 510 UV META laser scanning confocal microscope, a large format fluorescence microscope (Zeiss Axiophot 2) with attached high-resolution digital camera and a SLM 4800S life-time spectrofluorometer. The confocal microscope includes: an Axiovert 200M microscope; dry, water-, and oil-immersion high-resolution objectives for fluorescence and Normarski differential interference contrast observation; Ar, dual HeNe, and UV lasers; fluorescence filter sets for DAPI, FITC, TRITC, INDO-1, and SNARF; a scanning module with visible and UV acousto optical tunable filters, two independent fluorescence channels (2 PMTs), a 32-PMT array; and a stage incubator. This instrument is equipped for high-resolution detection of cellular and infectious agent-specific proteins and in particular for monitoring changes in their volume distribution relative to changes in physiologic parameters. A high-speed computer (Dell 530 work station with dual 1.8 GHz xeon processors) work station with two monitors and software for physiology, scan and 3-D imaging supports the image analysis activities within the OIC.  
 

The Molecular Genomics Core Laboratory provides services, technical support and advice to UTMB investigators in the area of gene expression analysis. This core has provided gene expression analysis through the use of affymetrix gene chips since 2000 and currently accounts for approximately 30% of all affymetrix assay utilization in the State of Texas.  The Molecular Genomics Core utilizes the affymetrix data mining software in providing additional support for the analysis of gene chip data and works closely with the Bioinformatics Program in developing more advanced computational analyses. This core also offers investigators an opportunity to select specific genes of interest and to use in the design of their own, custom microarrays.   
 

The Parallel Synthesis and Medicinal Chemistry Facility (PSMCF) was established in September 2004 with support from the Department of Pharmacology and Toxicology and the Center for Molecular Design. The PSMCF serves a two-fold purpose: 1) to provide a parallel synthesis facility with expertise in the synthesis of a variety of defined small/large molecule libraries that are commercially unavailable and/or unaffordable; 2) to provide a high-throughput and reliable source of Biologically active compounds to be tested. Using in-house medicinal chemistry expertise to make the necessary compound modifications improves their drug-like properties. The core utilizes state-of-the-art instrumentation, as well as a plethora of synthetic protocols amenable to compound library generation. In some cases, however, development of novel protocols is needed. This will be done through the use of broadly existent in-house organic chemistry expertise. The PSMCF covers a wide range of organic chemistries, purification protocols and analyses, as well as internal technical support for issues relating to organic synthesis.  
 

Proteomics Core Facility is one of 10 national proteomics centers that the NIH/NHLBI established with $15.7M of support, allowing UTMB to institute a new proteomics program.  The center focuses on developing new proteomics technologies for investigating a number of processes, including cancer development and the influence of stroma on surrounding cancer.  The UTMB Proteomics Center functions in close collaboration with the UTMB Biomolecular Resource Facility.  
 

The Recombinant DNA Laboratory provides UTMB investigators with a variety of essential services and technical support in the area of recombinant DNA techniques.  Services include the production of plasmid and phage DNA, competent cells, transformation and screening for recombinant plasmids and DNA sequence analysis.  The Recombinant DNA Laboratory offers technical support in bacterial and baculovirus expression, site directed mutagenesis, construction of transgenic and null gene plasmids and various PCR based technologies.  
 

The Research Histopathology Core (RHC), established in 2001, provides analytical morphology related services to the research teams at UTMB. The facility is equipped with the latest available instrumentation and operated by highly skilled personnel, who can assist with antibody searching, experiment design, tissue preparation, data acquisition, digital photographing, and paper preparation or develop special protocols to fit researchers’ needs. One of the latest additions to the RHC is the Automated Comet System, a state-of-the-art robotic system optimized for automatic detection and measurement of cells using application-specific, computer-based, imaging-processing algorithms. It is a sensitive method to measure DNA damage in single cells at the strand break level, and virtually any eukaryotic cell can be used for analysis. The Comet Assay has been widely used for in vivo/in vitro, aging, radiation effects, drug treatment, antioxidants, biomonitoring and envirogenomics studies – aquatic biology (fish, oyster, shrimp), etc.  
 

Research Technology Support (RTS) provides specialized electronic hardware and interface for off-the-shelf devices, attaching all sorts of things to computers. The group also repairs and maintains laboratory equipment, such as centrifuges, incubators, physiological monitors, scales, microscopes, etc. RTS also provides preventive maintenance and Electrical safety inspections. Through the complete machine shop, with CNC capabilities, RTS also works with investigators to fabricate structures in Lexan, Plexiglas and standard and exotic metals for specialized research needs.  
 

Sealy Center for Cancer Cell Biology Cores

Transgenic Mouse Laboratory was established in 1983 to serve UTMB investigators interested in establishing human cancer xenograft lines and studying the effects of various agents on tumor growth in an in vivo model.  Because tumors generally maintain their histology and human karyotype and because human drug sensitivity or resistance are stable when tumors are transplanted to the nude mouse, the laboratory both enhances and promotes research related to human cancerous tissue.  In addition, it enables investigators to apply for grants and contracts related to human cancer research, many of which specifically require experimentation on nude mice.  The establishment of uncommon cancers can be facilitated by transplantation into the nude mouse.  Finally, various agents and drug delivery systems may be tested using this in vivo model.   
 

Specific objectives are to: assess specific therapies and drug delivery systems on the growth of different human cancers in nude mice; provide source materials for human tumors; use the T-cell-deficient nude mouse for immunological studies; provide an immunocompromised in vivo model; assess developmental growth and gene expression of normal tissues from other species; and facilitate the establishment of uncommon tumors resected from patients 
 

Many colorectal, gastric and pancreatic cancer xenograft lines have been established and are available for analysis and experimentation.  In addition, novel human endocrine cancers have been established that represent, in some instances, one-of-a-kind tumor models.  The majority of tumors are transplanted to the subcutaneous tissue of the back or flank.  This allows for ease of analysis and measurement.  Further, tumor models are available that involve implantation into the abdomen and mimic human metastatic cancers with metastasis to the liver or other organs.  Injection of test agents can be achieved by the oral, subcutaneous, intraperitoneal or intravenous routes.  Novel methods of drug delivery may be relatively easily assessed using nude mice.  
 

Real-Time PCR Core Facility offers a full complement of real-time PCR (polymerase chain reaction) services including primer and probe design and order, preparation of real-time PCR reactions, and data analyses for gene expression (DNA and RNA samples), as well as allelic discrimination. The PCR core facility has the following major equipment available: Applied Biosystems (ABI) PRISM 7000 sequence detector with a Dell Pentium III laptop computer; a Dell Pentium IV desktop computer installed with the ABI PRISM 7000 SDS (sequence detection system), PrimerExpress and file builder software.  
 

The UTMB Tumor Bank is housed in the Sealy Center for Cancer Cell Biology as part of our efforts to facilitate cancer research at UTMB. Collection of tumor tissues is a collaboration of the SCCB and the Division of Surgical Pathology. This bank contains >2,000 different specimens of various tumor-types, The Human Tumor Bank Core provides tissues for cancer-related research approved by the Institutional Review Board (IRB) and the Biological Safety Committee for using biohazard materials. In addition, this service promotes material-sharing and provides assistance on cancer tissue-related research.  
 

The Sealy Center for Structural Biology and Molecular Biophysics (SCSB) Cores aid scientists interested in elucidating the basic relationships between macromolecular sequence, structure and function, with a goal of leveraging this information into the understanding and treatment of disease.   The basic research within SCSB combines thermodynamic, kinetic and structural data about biomolecules and their complexes to understand important biomedical processes. The structural and dynamical basis for molecular recognition, signal transduction, protein folding and allosteric regulation is studied by x-ray crystallographic, nuclear magnetic resonance, and cryo-electron microscopic techniques, solution thermodynamics and advanced computational tools. 
 

The Computational Biology Core in SCSB provides state-of-the-art computational resources to researchers and to students who need extreme computing power. The power house of the Core is a 30 processor Linux cluster, which provides parallel-processing capabilities with total of 84 billion floating point operations per second, 40 GB of distributed memory and 1.6 TB of total storage space. The cluster also has centralized file-server capabilities and a tape library with 400 GB of storage space to archive and secure data. Peripheral devices include scanner, printers, color printers and tape drives. All computing resources are connected to the UTMB network, so other workstations on campus can easily access the resources of the Core. Scheduling is available online.  
 

The Cryo Electron Microscopy Core, on the first floor of the Medical Research Building, has brand-new laboratory space featuring a BSL-3 room for viral and pathogen work. The Laboratory has three JEOL cryo-electron microscopes, used for imaging of macromolecular complexes, cell organelles and other biological systems in their natural environment in vitrified state. The high-resolution JEM2200FS is located in the BSL-3 facility and permits structural imaging of pathogens. Unique to the core is the W. M. Keck Center for virus imaging with BSL-3 containment, the only cryoEM facility in the U.S. designed for high-resolution structural studies of wild type infectious agents. The JEM2100 is available for imaging of non-pathogenic targets. A lower resolution JEM1010 microscope is available for preliminary screening. Microscope scheduling is available online.  
 

The NMR Spectroscopy and Imaging Core in SCSB has three instruments for structural and biophysical studies that can be customized in a number of ways, including:  relaxation measurements, chemical shift perturbation, hydrogen exchange, and solution structure determination. The SCSB NMR instrumentation is housed in a dedicated two-story facility called the Dockside building. Instrumentation includes a Varian 800MHz (with a HCN CryoProbe), a 750MHz and an Inova 600 MHz NMR spectrometer. Both of the 800 and 750 MHz instruments are capable of HCN triple-resonance experiments with 2H decoupling. Scheduling is available online. 
 

The Solutions Biophysics Core in SCSB is equipped with a Beckman Analytical Ultracentrifuge XL-A to monitor the hydrodynamic properties of biomacromolecules and protein-protein interactions. In addition, the core has a MALDI-TOF Mass Spectrometer to monitor structures of biomacromolecules in solution.  Mass spectrometry is now used as a routine analytical assay of protein sequence and as a probe of structure. Mass spectrometry is the final test of protein sequence, and homogeneity after expression and purification. However, examination of the proteolytic products of a protein can reveal many things. A simple limited proteolysis may reveal domains or disordered regions. Attachment of specific proteolytic agents to a protein can reveal which elements are in proximity, and thereby provide specific structural information in the absence of NMR or crystal data.  Solution biophysics and thermodynamics techniques are used as primary research tools and to guide structural studies. 
 

The Membrane Protein Lab provides services through expertise and experience in membrane proteins, as well as water soluble proteins, via collaboration. Services include over expression of membrane proteins in heterogeneous systems (bacteria, yeast, invertebrate and vertebrate animal cells); isolation and purification of the over expressed proteins for structural and advanced functional studies; crystallization of membrane protein as well as water soluble proteins by lipidic cubic phase and other conventional methods; structure determination; screening of drugs against membrane protein targets; computational modeling of secondary structure of proteins; and atomic force microscopy, imaging & energetic of protein folding.  
 

X-ray Crystallography Core in the SCSB provides two x-ray area detector systems, each with an ultra-fine-focus high-brilliancy x-ray generator and focusing multilayer optics. The first area detector is a MacScience DIP2030H-VLM dual 30cm diameter Imaging Plate detector. This system is suitable for protein crystals of 30 to 400 Å cell dimensions, which diffract up to 1.3 Å resolution. The second detector is a Bruker SMART 2k CCD, which can reach up to 0.9 Å resolution. For enhanced data, there is a choice of sample cooling systems. Both systems are equipped with a Cryo Industries of America CRYOCOOLER. A 4 °C Cold Air refrigerated cooling system is available for samples which cannot be frozen, or do not require freezing.  Diffractometer scheduling is available online.  This SCSB Core also has a Crystallization Chemist on staff to help with difficult crystallization problems. 
 

The Synthetic Organic Chemistry Core provides an on-site, cost-efficient, full-service, chemical synthesis facility to synthesize defined DNA lesions, bioconjugates and small organic molecules that are unavailable or prohibitively expensive.  The SOCC is part of the NIEHS Center at UTMB and has been in operation since March 1998.  Since then it has synthesized more than 500 different organic synthesis products for a number of researchers and research cores on campus.  The SOCC has synthesized many modified nucleosides, metal chelators, steroid analogs, modified peptides, enzyme inhibitors, as well as hard to find organic analytical standards and reagents. The lab is a shared chemical synthesis facility open to researchers who need assistance with chemical syntheses, wish to use the lab’s resources, or need technical supervision and/or training of technicians on synthesis research projects.  The lab, located in the Basic Sciences Building, adjacent to the Truman Blocker Medical Research Building, houses equipment for multi-step organic chemical syntheses from mg to 100g scales, modified DNA syntheses, HPLC analyses and purification, photochemical reactions, flash chromatography, rotary evaporation, distillations, sublimations, titrations, temperature controlled and high pressure reactions.  
 

The Tissue Culture Core Facility is a division of the Department of Microbiology and Immunology. The core supports UTMB investigators in a time- and cost-efficient manner. The facility provides products for tissue culture, molecular biology, and immunology research from multiple vendors. Other services include heat in-activation of serum, mycoplasma detection and eradication, tissue culturing, and cryogenic preservation and repository of cells.  
 

The Transgenic Mouse Core Facility is designed for generation of transgenic and knockout mice, as well as knockout embryonic stem (ES) cell lines. The core also conducts cryopreservation of mouse lines, rederivation and maintenance of mouse lines generated by the core, and genotyping of mice. (See also Sealy Center for Cancer Cell Biology mouse core.) 
 

RESTRICTED CORES 
 

Galveston National Laboratory, scheduled to open in 2008, is a $167M structure ($110M from NIH/NIAID) housing BSL-2, BSL-3 and BSL-4 laboratories to study pathogens and develop countermeasures and diagnostics against them. This national laboratory will complement ongoing studies with national and international recognition in the Center for Biodefense and Emerging Infectious Diseases.  While the goal of this large enterprise is to address important issues related to emerging infectious diseases and the development of countermeasures to biological threats, it is anticipated that this laboratory will help with other initiatives on campus by developing improved diagnostic, therapeutic and vaccine countermeasures.  Much of this work will be translational in nature and will draw heavily on the genomics, proteomics and structural biology capabilities of the institution in the vaccine and new drug discovery process.  Therefore, the platform will be in place for the rapid development of new drugs and vaccines which will also assist other programs that are evaluating ways to translate discoveries into novel therapies for treatment. Laboratories will incorporate the most advanced technologies in biomedical research targeted to diagnostics, therapeutics and vaccine development, including a high-field animal MRI, confocal microscopy, high-resolution cryoelectron microscopy and novel robotic technologies, all in BSL-4 environments. UTMB is the only institution to be awarded both Regional Center of Excellence and National Biocontainment Laboratory grants.  
 

The Robert E. Shope, MD, Laboratory in the John Sealy Pavilion for Infectious Disease Research was the first full-sized biosafety level 4 (BSL4) facility on a university campus in the United States. The 2,000 square foot laboratory accommodates research on highly infectious, potentially lethal agents, such as the highly pathogenic hemorrhagic fever viruses. The full-body suited laboratory requires entrance and egress of personnel through a chemical shower. Equipment and samples move through double-door autoclaves, an air lock, and an immersion tank. A high intensity Cobalt-60 irradiator inactivates infectious samples for study at lower containment levels on certain types of assays, such as antibody testing and proteomics. All operating and safety protocols are in place and approved by the Institutional Biological Safety Committee, as is a training program. The laboratory, housed in a limited-access support building, is divided into two approximately equal parts. One half is equipped as a classical and molecular virology laboratory. This area has all the equipment needed for virological studies, including incubators, biosafety cabinets, centrifuges, balances, microscopes, and freezers. A small section houses centrifuges and a reference collection of BSL4 virus strains. The Shope laboratory will be physically connected to and part of the research efforts of the GNL.

    

The Emerging and High-Risk Pathogens Core (EhRP) oversees operations and management of the GNL BSL4 facilities and is responsible for organizing and setting priorities for all experimental work and procedures performed within the BSL4 facility.  That includes training personnel, managing infectious agent stocks, providing service and field activities related to BSL4 agents, and managing waste generated in BSL4. The work performed in the GNL BSL4 will significantly enhance national preparedness in developing countermeasures, such as vaccines, therapeutics and diagnostics, against high-risk pathogens by advancing our understanding of basic mechanisms of pathogen biology and pathogenesis. The EHRP Core will also is a host training and working site for U.S.-based and international scientists, technical personnel, and pre- and postdoctoral fellows who require practical laboratory experience or would like to pursue BSL4 research, but do not have facilities available.  
 

The Biological Safety Level 3 (BSL3) Core oversees operations and management of the BSL3 laboratories. These laboratories are capable of supporting basic-, GLP- and enhanced BSL3 research projects on bacterial, fungal, and viral agents classified as Category A, B, or C biological agents. Current research projects in the BSL3 core focus on the investigation of the interactions between host and pathogen; development of vaccines and therapeutics; diagnostics; and biodefense-related projects. A strength of the core is that it provides a functional laboratory site and scientific expertise for the training of scientists (both national and international), postdoctoral fellows, and graduate students seeking to work on select agents. This core interacts closely with other GNL cores, with the goal of understanding microbial pathogenesis and fostering the development of countermeasures against select agent pathogens. 
 

The Preclinical Studies Core provides research support services and training to sustain a highly skilled cadre of personnel with expertise in the development of animal models, host-pathogen relationships, and for testing vaccines, diagnostics, and therapeutics against live agent challenge in a GLP or GLP-like environment. The GNL is designed to offer maximum flexibility, incorporating BSL2/3/4 laboratories, with supporting animal research laboratories, necropsy room, and associated support space. However, we recognize the need to supplement or replace studies involving animals with alternative, scientifically valid approaches wherever possible, and to maximize the information gained from such studies. The decision to establish and utilize a highly efficient, Preclinical Studies Core facility was based on efforts to limit the number and variety of animal species. Technologies including surgically implanted telemetric devices, laparoscopic, endoscopic, and ultrasound guided tissue biopsies will be used to provide real time data with minimally invasive techniques. The Core Director, in consultation with the GNL Administration Core, will direct and prioritize all activities with the aim of assisting NIAID-funded biodefense investigators from institutions lacking appropriate biocontainment facilities, technology, or training. 
 

The GNL Insectary Services Core (GIS) is designed to enhance the capacity within the United States to rapidly evaluate the potential role of arthropods in the transmission of biological agents introduced into the US.  The mission of the GIS is “To facilitate research on vector-borne pathogens that are classified as being of national importance with respect to public health in the U.S.” An important goal of this core is to train personnel in research techniques using arthropod vectors under high and maximum biocontainment conditions.  A major activity will be the development of research SOPs and protocols, and the adaptation of specialized equipment for use with potentially infectious vectors under strict containment conditions. Basic and applied research and training, to expand the pool of scientific expertise, is conducted in the state-of-the-art GNL facilities. The readily accessible core is specifically designed, equipped, managed and operated to serve as a highly efficient national resource for the NIAID’s Biodefense Network, and other federally and non-federally supported biodefense and emerging infections research programs. In the event of a national bioterrorism or emerging disease emergency, the core will offer expert consultation to local, regional, state, and national entities involved in first response and biological incident management. The core director will direct and prioritize all activities with the aim of assisting NIAID-funded biodefense investigators from institutions lacking appropriate biocontainment facilities, technology or training for manipulating arthropod vectors. 
 

The Assay Development Core (ADC) provides the expertise and equipment needed to assist GNL researchers in translating basic science knowledge and discoveries into practical measures that will improve human health. One of the main functions of the ADC is to assist in developing in vitro assays that utilize new targets and technologies. As part of this support, the ADC will work to develop assays from the research bench top to a standardized, reproducible and validated format in which they will be suitable for use in medium to high throughput screening studies. The second major function is conducting high throughput screening studies using the assays that it develops.  Further, the ADC refines and validates established assays under both BSL2 and BSL3 containment conditions.  The core also has capacity to conduct small scale studies under BSL4 containment. In the short term, any small molecular compounds to be screened in this way likely will be obtained from available NIAID libraries. However, the ability to conduct in vitro screening studies above BSL2 containment, as well as to conduct these studies with select agent pathogens, will be an important resource to GNL, NIAID Biodefense Network scientists, and external entities. Thus, the ADC will work closely with the UTMB Center for Technology Development, and the GNL Administration Core to maximize the availability of new assays and screening capability to external entities. In fulfilling this function, the ADC is anticipated to function via fee-for service agreements and licensures that will partially offset future development and instrumentation costs.   
 

The Experimental Pathology Services Core (EP) functions as a critical component of the GNL’s research support services. It is staffed with trained and experienced experimental pathologists, histotechnologists, and specialized microscopists. They provide histology, advanced microscopy services, and flow cytometry support, offer diagnostic services to establish specific etiologies for human disease syndromes, and manage a small scientific store that offers tissue culture reagents and services. In addition, training will be offered to help GNL investigators acquire specific skills in various microscopy and flow cytometry techniques. Histology services are a key component because many immunohistochemical techniques require the skill and experience of trained technologists. The EP Core staff is able to advise investigators on sample preparation and troubleshoot staining methods. The core will insure consistent handling and processing of tissue specimens required for animal model development and for studying the pathogenesis of NIAID Category A-C agents. It employs strict quality control measures and practices consistent with CAP, CLIA, and GLP guidelines. The core also will establish a tissue diagnostics reference capability for the diagnosis of human disease that will be of great value in the response of the GNL to a biodefense emergency or outbreak of a novel naturally transmitted infectious disease. Users may request full technical services in electron microscopy (transmission and scanning) in order to obtain whatever photomicrographs and analyses they need for given specimens, or they can work independently on the EP Core's microscopes, specimen preparation equipment, and other facilities after appropriate training. The core also manages a Tissue Culture Core Facility satellite in the GNL that will offer cell culture services, including mycoplasma testing on a charge-back basis, will operate a scientific supply room for media, sera, and enzymes; and will provide dangerous goods shipping and receiving services. 
 

The Imaging Core provides services in two major areas: (1) whole animal imaging technologies in support of the biodefense and emerging infectious disease research mission of the GNL, and (2) advanced optical imaging technologies (especially multi-photon microscopy and laser-scanning confocal microscopy) to visualize microbial and viral components within tissue sections as well as in vivo, in living animals at BSL2/3/4 levels of biocontainment.  
 

The Aerobiology Core has the capability to aerosolize BSL3 and BSL4 pathogens (bacteria or viruses) to study their affects. The core focuses on the development of GLP or near-GLP compliant methodologies that will facilitate the validation of interventions and generate high quality data suitable for submission to regulatory agencies.  
 

The Regulatory Services Core (RSC) oversees and coordinates all functions within the Galveston National Laboratory (GNL) that require compliance with regulatory guidelines for the purpose of supporting product licensure. Initially, the vast majority of this effort will focus on implementation and maintenance of studies conducted in accordance with the FDA’s Good Laboratory Practices (GLP) guidelines outlined in the Code of Federal Regulations, Title 21, Part 58 (21 CFR Part 58).  The specific scope and requirements of such studies cannot be anticipated, although it is likely that these will involve validation of animal models for biodefense and emerging infectious disease agents, as well as pre-clinical testing of candidate vaccines and therapeutics, including testing under the FDA Animal Rule (21 CFR Parts 314 and 601).  Furthermore, these activities likely will occur at BSL3/ABSL3 and BSL4/ABSL4.  Hence, the potential scope of GLP research activities within the GNL is very wide and will require input and support from most, if not all, laboratory and supporting Cores.   
 

The Immunology Core facility provides immunological support services in conjunction with the UTMB Animal Resource Center for animal model development against emerging infectious diseases and diseases caused by Category A-C pathogens.  This core provides an array of support services that are unique and not currently available to GNL investigators through any other NIAID contracts or through commercial sources. 
 

The NIEHS Center Cell Biology Core (CBC), an established National Institute for Environmental Health Sciences (NIEHS) Center Service Core at UTMB, developed an infrastructure of core services for members of the NIEHS Center Research Cores. This core is dedicated to the development and delivery of state-of-the-art methods and technologies in cell biology to assist Center investigators in their mission. The wide range of diseases studied includes cancer, drug abuse, behavioral disorders, chronic inflammatory lung diseases, aging and age-associated diseases. Related research ranges from studies of molecules (damaged DNA, DNA repair proteins, transcription factors, drug metabolizing enzymes) and cells to those of whole animals and human populations. The core supports investigators from the Departments of Biochemistry and Molecular Biology, Pharmacology and Toxicology, Microbiology and Immunology, and the Sealy Center for Molecular Sciences. In addition to state-of-the-art equipment and methods, the key personnel of this core provide scientific and technical expertise that greatly benefits investigators in terms of experimental design, execution and interpretation. A particular strength of this core is to serve as an integrating umbrella to foster collaborative arrangements that cross departmental boundaries, and to facilitate productive interactions between basic and applied environmental sciences.  
 

Optical Imaging Laboratory has digital imaging systems that include confocal and wide-field optical microscopes: last generation Zeiss LSM 510 confocal microscope and spectral imager, capable of multicolor three dimensional fluorescence imaging for colocalization; fluorescence resonance energy transfer (FRET), and multispectral analysis of single cells or thick specimens. An advanced semiautomatic wide field imaging system is capable of quantitative time lapse studies combining multiple microscopy modes simultaneously. The upright wide field imaging system is equipped with color and monochrome digital CCD cameras, ideal for studies of fixed samples using color bright field, phase contrast, DIC and multicolor fluorescence. Image processing and analysis: The facility has 4 PC stations equipped with Metamorph and Image J imaging, and other graphical software. Fully assisted or independent operation: depending on user needs, we provide complete support for microscopy sessions as well as image processing and analysis; however we also allow more experienced users to perform their own experiments and observations. The lab is available 24 hours a day, 7 days a week. Online services are available via our website under “support and customization.” Training, supervision and consulting: We offer training on microscopy and digital imaging. Other equipment and services are available upon request. For example, we can install perfusion systems, temperature recording and control, micromanipulators and patch clamp recording setups.

Pepper Center Cores

The Metabolism Research Core supports and trains investigators in stable isotope methodologies for the measurement of metabolism in aging, and provides mass spectrometry analysis of amino acids, fatty acids, glucose and other metabolites, as specified for the Pepper Older Americans Independence Center (OAIC). Stable isotope tracers have become invaluable tools with which to investigate human metabolism. New kinetic models and analytical approaches developed in this lab investigate various aspects of glucose, fat and protein metabolism. The specific goal of this core laboratory is to make available mass spectrometry analysis for all projects involved with the Pepper Center and, more in general, in metabolism in aging. We will assist investigators in all aspects of tracer methodology necessary to use this approach to study metabolism in elderly individuals. We have all the equipment necessary to perform stable isotope enrichment measurements, including three quadruple gas chromatograph mass spectrometers with EI/CI/NCI interface and parallel FID, and a gas chromatography-combustion-isotope ratio mass spectrometer with a gas bench for IRMS analysis of breath and blood gasses. The staff has expertise in experimental design, performance and analysis of tracer studies, and in mathematical modeling. Furthermore, this core offers two courses through the Graduate School of Biomedical Sciences: one on Tracer Methodology (PMCH 6355) and one on Directed Studies in Metabolism (PMCH 6250). We also have an active research fellow program that includes one formal meeting per week and informal training. 
 

The Proteomics and Genomics Core Facility:

• Provides state-of-the-art experimental resources.
• Participates in the development of new procedures that will facilitate understanding of the molecular, genetic and Biochemical mechanisms of sarcopenia associated with aging.

The Recruitment and Measurement Core coordinates recruitment of subjects for studies by UTMB investigators affiliated with the UTMB Pepper Older Americans Independence Center (OAIC). Difficulty in accessing older subjects is a major barrier for clinical investigators who wish to study the elderly. Thus, this Core aggressively markets to other clinical investigators at UTMB the availability of older volunteers for clinical investigations, in addition to its primary goal of recruiting for the OAIC investigators. The Core also trains investigators in methods of recruiting older subjects for clinical research, particularly older minorities.

 
 

The Subject Recruitment and Retention Core:

• Assists OAIC investigators in the identification, planning and implementation of recruitment strategies;
• Provides a source of well-described older adults who meet the inclusion criteria of intervention development studies and pilot investigations;
• Facilitates the recruitment of minority subjects for clinical research by expanding existing subject recruitment sources;
• Assists in the development of new research and training activities related to conducting research in aging; and
• Provides information and education programs related to the recruitment and participation of human subjects in clinical research to multiple groups including investigators and potential subjects.

 
 

The Subject Recruitment and Retention Core involves the integration and coordination of three sources of older adult subjects: The Health of the Public Project, a population-based survey of older adults (> 75 years) in Galveston County; the Volunteer Registry supported by the Sealy Center on Aging at the University of Texas Medical Branch; and Community-based older adults including the Sealy Center on Aging Consortium of Nursing Homes. 
 

The Research and Career Development Core (RDC) provides career development training, supports pilot research projects, and coordinates use of the research cores by other investigators who are not receiving direct support from the Pepper Older Americans Independence Center (OAIC). The RDC has two potential targets: junior faculty and trainees in clinical and basic science disciplines relevant to aging; and established investigators with expertise highly relevant to aging research but not currently studying aging.  
 

The RDC takes different approaches to these two groups. For junior faculty, the RDC coordinates structured didactic training with the provision of appropriate mentoring. Junior faculty are assigned both research mentors and career mentors, the one to focus on the specific goals of the research project and the other to assist with defining overall career goals. Mentors are selected from among senior faculty in aging research. A major theme of the training program is linked to mechanistically driven research to evaluation of clinical outcomes. RDC activities involving more established faculty concentrate on providing opportunities and support for interdisciplinary collaboration, drawing investigators from other disciplines into ongoing studies of the OAIC.

 
The RDC supports investigators in a wide spectrum of clinical and basic science disciplines. We feel strongly that it is important to train individuals in different medical and surgical subspecialties to address research issues in their disciplines directly relevant to aging. UTMB has a strong tradition of rigorous academic research in surgery and the surgical specialties. Obviously, the overall research focus of this OAIC, developing interventions to preserve or improve muscle function, is of great relevance to surgeons and to intensive care physicians, such as anthesiologists. Similarly, there is need for a cadre of investigators in cardiology, oncology, nephrology, and other medical subspecialties to be addressing unique research questions relevant to the elderly within each of their disciplines.  
 
 

(last revised August 25, 2008)