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Stanford Report, May 31, 2000

Seventeen projects receive Bio-X funds

Stanford Transgenic Facility: The Stanford transgenic facility provides state-of-the-art services for the construction of transgenic mice. Transgenic animal technology is crucial for the evaluation of the function of genes in the context of developing animals. It has emerged as a key component in biomedical research, in development of therapeutic strategies for human and animal diseases and in drug discovery. Funds provided will upgrade the facility to allow provision of new services involving embryonic stem cell manipulation and gene targeting for the creation of knock-out and knock-in mice.

Principal Investigator: Michael Cleary (Pathology)

Cognitive Neuroscience Facility: This facility will meet the needs of a diverse group of neuroscientists from numerous departments in the schools of Humanities and Sciences, Engineering, and Medicine. These investigators have been brought together in large part because of advances in technology (fMRI, MEG and EEG). The technology has stimulated research in a wide variety of areas (magnetic resonance physics, signal and image processing, bioengineering, biophysics), in addition to the work in cognitive neuroscience per se. The new equipment, which will primarily be housed at the Lucas Center, includes eye-tracking equipment, a computational imaging lab, an EEG lab, psychophysiological recording instruments, a magnetic resonance simulator, and Quantitative Somatosensory Testing equipment.

Principal Investigator: John Gabrieli (Psychology)

Stanford Synchrotron Radiation Laboratory: The aim of this funding is to significantly enhance a new campus-wide core facility for macromolecular crystallography. This will be achieved through procurement of the most advanced 3X3 CCD X-ray detector system currently available in the world, and implementing it on the newly constructed Stanford/Scripps/SSRL crystallography beam line at the Stanford Synchrotron Radiation Laboratory. Such an acquisition will provide greatly enhanced scientific capability and higher operational efficiency for Stanford researchers interested in solving X-ray crystal structures of macromolecules.

Principal Investigator: Keith Hodgson (Chemistry)

Electron Microscopy Facility: This facility is needed to meet Stanford's acute and rapidly growing demand for a state-of-the-art shared electron microscopy (EM) resource. Transmission EM provides a unique capability to visualize cellular structures that are below the resolution of light microscopy, as well as the ultrastructure of viruses, macromolecular complexes and individual molecules. Scanning EM allows the direct observation of surface properties, and is important in biology, materials science and microfabrication. EM facilities presently available are antiquated and completely inadequate to support current needs in research and training. This funding will facilitate the acquisition of a state-of-the-art transmission EM, scanning EM and associated sample preparation equipment.

Principal Investigator: Harley McAdams (Developmental Biology)

Cell Sciences Imaging Facility: This facility in the Beckman Center is being given funds for the capital purchase of a 2-photon laser scanning microscope to enhance and extend available technologies for using fluorescent markers to visualize cells and tissues.

Principal Investigator: Susan Palmieri (Director, Cell Sciences Imaging Facility)

Fluorescence Activated Cell Sorting (FACS) Core Facility: Biomedical research requires an ability to separate and describe unfolding events in complex surroundings. Since the mid-1980s, the Stanford Shared FACS Facility (SSFF) has provided a state-of-the-art flow cytometry facility for immune system studies, molecular biology research, pre-clinical research, HIV-1 studies and a host of other enterprising studies in a variety of fields. This proposal seeks to expand and upgrade the capabilities of the SSFF by adding a 9-color, 3-laser high speed cell sorter and a 6-color, 2-laser non-sorting analyzer, and upgrading the central data store, data management and data access system of the facility.

Principal Investigator: David Parks (Genetics)

Stanford Magnetic Resonance Laboratory: This core facility provides nuclear magnetic resonance (NMR) instrumentation and expertise to the Stanford research community for the study of molecular structure, especially macromolecular structure, in solution. The applications of NMR straddle the fields of chemistry, molecular biology, physics, engineering and computing. This grant will facilitate the acquisition of instruments that will establish the Stanford Magnetic Resonance Laboratory as one of the best such facilities in the world.

Principal Investigator: Joseph Puglisi (Structural Biology)

Tissue Bank: The goal of this new facility, to be developed in the Department of Pathology, is to create a Stanford resource for obtaining, classifying, storing, retrieving and experimenting with human and laboratory animal tissues. The research supported by such a facility would include state-of-the-art genetic, proteomic, biochemical, structural and bioengineering analysis of tissues.

Principal Investigator: Jan Matthijs van de Rijn (Pathology)

Mass Spectrometry Facility: The goal of this facility is to provide a critical expansion of the limited mass spectrometry facilities at Stanford, allowing broad-based, high-throughput proteomic and small molecule mass analysis for a wide range of applications in macromolecular chemistry, pharmacology and bioengineering. Mass spectrometry is becoming the most comprehensive and flexible tool for molecular characterization of small molecules and macromolecules including proteins. The acquisition of a Q-TOF mass spectrometer will allow both proteomic analysis and high throughput identification of small molecules. Coupling the development of this core to other modern instrumentation cores (including multiplate readers and a basic plate robot) is expected to allow a flexible facility for high-throughput mass analysis, possibly coupled with other assays.

Principal Investigator: Tom Wandless (Chemistry)

Microarray Facility: Tools for capturing the functional state of a collection of cells have advanced rapidly in the last decade. Prominent among these are a variety of DNA microarray technologies. In particular, complementary DNA microarrays have made it practical to quantify the expression of thousands of genes in parallel. This mode of analysis has been used to observe gene expression variation in a variety of human tumors and other tissue as well as a number of single-cell organisms and plants. The facility will provide Stanford researchers easy access to the most advanced functional genomic technologies at nominal cost. Researchers will be able to access the facility at a number of levels.

Principal Investigator: Michael Fero (Genetics)

Surface Plasmon Resonance Facility: This new facility will acquire a Biacore surface plasmon resonance instrument. This instrument detects and monitors binding between two or more biomolecules, in real time, without the use of molecular labels. It records in exquisite detail the kinetics of binding (i.e., rates of association and dissociation) between most biomolecules and macromolecules (small molecules, peptides, proteins, carbohydrates, RNA, DNA, lipids, vesicles and even whole cells) in aqueous solutions under physiological conditions. It also measures the strength of binding between biomolecules (i.e., affinity constants) and is often used to search for novel binding partners (i.e., to search for a unknown receptor for a known ligand). The instrument is fully automated and performs dozens of these extremely sensitive measurements in a very short amount of time (hours) and with minimal quantities of material; there is no other instrument available that provides this kind of data with such ease, speed and versatility.

Principal Investigator: Michael Rexach (Biological Sciences)

Small Animal Imaging Laboratory: The mission of the small animal imaging shared resource is to support the multidisciplinary research program in molecular and cellular imaging through application and advancement of technologies for in vivo biological assessment and imaging in animal models of human biology and disease. The imaging resource will provide Stanford scientists and engineers with a suite of imaging tools for in vivo analyses in living animal models and further the development of imaging technologies. Imaging strategies that link in vivo analyses to the high throughput ex vivo assays of DNA microarray technologies, advanced confocal and two-photon microscopy and ultra-flow cytometry will be advanced for an integrated set of high throughput in vivo and ex vivo analyses. The results from these combined imaging modalities will be used to define the complex relationships between molecular events, anatomy and function, in both animals and in humans.

Principal Investigator: Chris Contag (Pediatrics)

Biofilm Laboratory: The laboratory will combine engineering and biomedical approaches to study biofilms. The objectives of this biofilm laboratory are: a) to use state-of-the-art optical and genomic tools to elucidate the physiology, metabolism and genetic interactions of microbes in biofilms; b) to determine physical-chemical parameters of biofilms, such as density, packing, shear stress and chemical gradients; and c) to integrate both approaches into a comprehensive, quantitative view on biofilms with capabilities for development of rational conceptual models and numerical simulation of biofilm structure and function. A biofilm laboratory facility is crucial for ongoing biofilm research and will serve as a platform for a campus-wide research thrust on microbial biofilms.

Principal Investigator: Alfred Spormann (Civil and Environmental Engineering)

Product Realization Laboratory (PRL): The PRL is a teaching laboratory on campus that supports the design and fabrication of prototype devices. In the past, there has been almost no biomedical engineering activity in the lab and little activity from medicine or biology. The funds given will enhance the PRL to support a new range of medical and biological applications. The enhancements include the addition of capabilities to manufacture small-scale plastic and metal parts. This will leverage an existing core facility and provide a new resource for future biomedical applications and engineering education.

Principal Investigator: David Beach (Mechanical Engineering)

Supercomputer and Immersive Visualization Facility: Stanford is establishing a new interdisciplinary program in biocomputation. This program builds upon the world-class engineering, medicine and science departments located in close proximity to each other. Two critical and inextricable components of a world-class biocomputation center are supercomputing and advanced visualization. It is proposed to acquire a large parallel computer (256 processors) and six network-connected "Immersive Visualization Work-benches" for this facility. The computer will enable basic and clinical research efforts ranging from subcellular and cellular level computing to organ system level computing. The workbenches will provide unprecedented visualization capabilities in six locations and will be configured with haptic interfaces to enable human interactions with computer models in applications ranging from feeling forces exerted on single molecules to developing realistic patient models and environments for surgical training.

Principal Investigator: Charles Taylor (Surgery)

Parallel Computer Cluster for Computational Biosciences: The facility will involve the acquisition of a computer resource, comprising many hundreds of desktop processors linked together, for computationally intensive computational biology at Stanford. Applications include simulation of biomaterial aging, nanotube biosensors, protein folding and protein design.

Principal Investigator: Kyeongjae Cho (Mechanical Engineering)

Bioinformatics Facility: This existing resource at Stanford has successfully catered to the bioinformatics needs of more than 130 laboratories on campus from 37 different departments with a wide variety of hardware and software needs. It also provides educational opportunities to help researchers utilize the software effectively. The current funding allows expansion of this facility's capabilities into genomic and functional genomic data analysis, and enhancement of consulting services currently provided to assist Stanford researchers with customized needs.

Principal Investigator: Lee Kozar (System Software Developer/Molecular and Genetic Medicine) SR