Facilities
We have a wide range of facilities at the Universit of Guelph that facilitate the high level of interdisciplinary research that takes place within BIG and at the University of Guelph.
Atomic Force Microscopy 
Atomic force microscopy (AFM) uses a micro-fabricated cantilever monitored by an optical lever system to allow three dimensional topographical and mechanical measurements of specimens in air or in liquid, on the nanometer scale. The AFM Facilities available to members of BIG are currently located in the Dutcher Lab in Room 103 of the MacNaughton Building, and comprise two atomic force microscopes: a Veeco (Digital Instrument) Dimension 3100 AFM, and an Asylum Research MFP-3D AFM. The Veeco instrument is equipped with a top-view optical video microscope and a motorized stage for easy sample manipulation and routine collection of topographic data. The Asylum instrument is set up on a Nikon Eclipse TE2000-U Inverted Research Microscope for simultaneous epifluorescence imaging of the sample, and has closed-loop scanning capabilities for extremely accurate tip positioning and force measurements. Both microscopes have a wide variety of applications in the physical study of polymer films and of bacterial cells. In 2006, through a CFI grant, these AFM systems will be upgraded to make them the best possible for this type of work.
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Biomechanics Facilities
The newly installed (July 2004) six camera VICON™ 460 motion analysis system used for characterizing human movement is located in an approximately 16 square meter small volume capture laboratory in the School of Engineering. The six Mcam2 cameras are attached to the walls along cylindrical bars at varying levels with permanent camera mounts to prevent lab personnel and subjects from tripping on cabling (Figure 1). Six Manfrotto tripods are available allowing the VICON system to be used in other locations. A VICON™ workstation can be used to collect signals synchronized using a 64 channel analog to digital conversion board from various analog inputs including: an eight channel Noraxon™ telemetered EMG system for monitoring skeletal muscle activity, strain gauges for monitoring joystick strain, load cells, and Biometrics™ goniometers for measuring joystick angles. The lab also contains a Microscribe™ 3D digitizer which is used for some VICON™ validation work as well as other animal and human  cadaveric studies.
Also available is an Instron 8872 Axial Servohydraulic Dynamic Testing System which is located in a secure Biohazard laboratory within the School of Engineering since it can be used for human cadaveric materials testing.
Funding to purchase the VICON™ and Instron 8872 Axial Servohydraulic Dynamic Testing systems was obtained from Canadian Foundation for Innovation New Opportunities and Ontario Innovation Trust grants. Funding to purchase the Noraxon telemetered EMG system was provided by NSERC.
To the right: subject sitting in mock-up of heavy equipment chair and joystick; circular markers are for monitoring the subject and joystick kinematics; green electrodes with wires coming off of subject are for monitoring muscle activity (EMG); wires coming off of joystick stem are to monitor strain in joystick.
The newest pieces of equipment in Dr. J.P. Dickey’s Joint Biomechanics Lab are two parallel robots. The word ‘parallel’ means that the robot’s mechanical links are arranged in parallel to each other, unlike the more common arm robots whose links are arranged in series. These robots were purchased from Parallel Robotics Systems Corporation within the Biomedical Science Department’s grant from the Canadian Foundation for Innovation (Dr. M.B. Hurtig from Clinical Studies was the co-investigator for this purchase).
The robots themselves look like large tables sitting on cylinders. However, the table’s ‘legs’ move about the large cylinder’s rim, causing the ‘table-top’, known as the end-effector, to translate and rotate in six degrees of freedom. One of the robots that is mounted vertically on the wall is currently being used in testing biological cadaveric joints; one bone of the joint is secured to the end-effector and the other is rigidly mounted to the frame surrounding the robot. Since most biological joints can move in six degrees of freedom or less, this robot is a huge stepping-stone in bringing the physiologic environment into lab-based investigations. The robotic system is currently being used to determine the load sharing between structures of the knee joint during physiologic loading. This line of research is evaluating the effects of osteoarthritis on knee joint function.
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Computational/Computing Facilities
Mathematics and Statistics Group
A variety of computer platforms are available to the members of the Biomathematics group, ranging from desktop workstations and PCs, to powerful parallel computers. The University of Guelph is an active member of SHARCNET (http://www.sharcnet.ca), a high performance computing consortium spanning 11 academic institutions in Southern Ontario. The software
available to BIG students includes: compilers and development tools, high-end visualization software, mathematical and scientific software (computer algebra systems, numerical software).
Physics and Chemistry
We have expertise on atomic resolution molecular dynamics on biological systems using CHARMM and GROMACS, symbolic manipulation and visualization software such as MAPLE and ab initio calculations on molecular structure using quantum chemistry programs such as GAUSSIAN. Furthermore, a variety of tools exist for in-house software development. Depending on the specific application, these calculations can be carried out on hardware ranging from the 1500 hundred CPU SHARCNET parallel supercluster (http://www.sharcnet.ca) to a 50 CPU minicluster available to members of our group to departmental desktop PC’s.
Computing and Information Science
The department has about 200 PC-type networked computers for use by graduate students. In addition, we have the Grid/parallel computer for high-intensity computation from SharcNet. The university also has a dedicated microarray facility.
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Confocal Microscopy
Dr. Marc Coppolino’s confocal microscope is now part of the College of Biological Sciences’ (CBS) Confocal and Imaging Facility. This facility supports the high resolution imaging of many different types of biological samples (living or fixed), and available for use by BIG faculty and graduate students. Dr. Coppolino’s microscope is a Leica SP2 system, inverted, with Argon and HeNe lasers, and is housed in the Advanced Analysis Centre on the first floor of the Science Complex. This instrument complements the facility’s other microscopes; a Leica SP2 upright system (with three lasers) and two standard epifluorescence microscopes, all of which are located in the basement of the Axelrod Building. These instruments will be moving to the Advanced Analysis Centre on completion of Phase 2 of the Science Complex. The facility will also be adding a new state-of-the-art multi-photon confocal microscope system by the end of 2005.
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DNA Sequencing Facility
Visit the DNA Sequencing Facility homepage
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Electron Microscopy 
The EM Facility available to members of BIG is part of the NSERC Guelph Regional Integrated Imaging Facility (GRIIF), originally established in 1982 by Dr. Terry Beveridge, with an award of an NSERC major installation grant. This is a national facility that offers the most advanced electron microscopy to users. Currently located in Room 1199 of the Thornbrough Building, the facility boasts three transmission electron (TEM) microscopes: a Philips CM10 TEM, a Philips EM400T TEM. The latter instrument is equipped with an energy dispersive X-ray spectrometer (EDS), and a Leo 912AB energy filter TEM capable of cryogenic work, electron energy loss spectroscopy (EELS), electron spectroscopic imaging (ESI), and selected area electron diffraction (SAED), capturing images digitally using a post-column slow-scan CCD camera. All of these instruments may be used for the visual examination of samples from the life sciences, geological or material sciences. In 2006, we will be obtaining a FEI G2 F2O field emission system that will be a dedicated cryo-TEM with single particle and tomographic capabilities.
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Fluorescence Spectroscopy
Steady-state and kinetic fluorescence
Time Resolved Fluorescence
Time-resolved fluorescence measurements are widely used in the study of protein structure and dynamics, since they often provide information that cannot be obtained by steady-state experiments. For example, static and dynamic quenching can only be distinguished by measurements of the lifetime of the fluorophore. Fluorescence resonance energy transfer (FRET), which is used to estimate inter-and intra-molecular distances between donor and acceptor fluorophores in proteins, is also best studied using time-resolved measurements of donor intensity decays. The presence of multiple decay components, each with a distinct lifetime, can provide valuable information on the different environments co-existing within the protein structure. Time dependent decay of fluorescence anisotropy is another very informative technique, especially in the context of membrane proteins and bilayers. Time-resolved fluorescence spectroscopy is a powerful technique that should be available to all researchers who use fluorescence as an experimental tool. The current lifetime instrument is a PTI LaserStrobe model GL3300 (Photon Technology International, South Brunswick, NJ) and the excitation source is a pulsed nitrogen laser, operating at 10 Hz and coupled with a dye laser.
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Fourier Transform Infrared (FTIR) Spectroscopy 
The time-resolved difference FTIR (Fourier-transform infrared) spectrometer allows researchers to follow biochemical transformations of proteins and lipids in real time. The power of difference infrared (vibrational) spectroscopy is that it provides specific information at the atomic level, enabling one to look at vibrations of individual actively changing bonds, against the background of the whole protein. Good examples of such experiments include determination of the protonation states of individual aspartate and glutamate residues at a catalytic or transport site, or following conformational changes of single amide bonds of a protein backbone. FTIR of proteins can be further enhanced by sophisticated band assignments using isotope labelling and site-specific mutagenesis. The instrument has additional features such as vacuum bench (lower noise), high time resolution (a few nanoseconds), and Raman spectrometer.
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Genomics and Microarray Facilities
Visit the Genomics and Microarray Facilities homepage 
Biomek 2000 liquid handling robot
CEQ8000 8-capillary Genetic Analysis System
Virtek Chipwriter Professional Arrayer for the preparation of custom slides
Agilent 2100 Bioanalyzer
Genepix 4000A scanner
Genetraffic data server for analysis of microarray results
Services
Array Services for custom array design and printing
Gene Expression Service (label, hybridize, scan and analyze)
Training and ongoing assistance in use of the Axon scanner
Training and ongoing assistance in use of Genetraffic and
SAM (Significance Analysis of Microarrays)
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MALDI-TOF Mass Spectrometer
Visit the MALDI-TOF Mass Spectroscopy homepage
Bruker Reflex III MALDI-TOF:
Ionization: Matrix assisted laser desorption/ionization, 337 nm Nitrogen laser
Detector: Time of flight, positive or negative ion analysis
Manufacturer: Bruker Daltonics
Types of macromolecules: protein digests, proteins, DNA, carbohydrates
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Nuclear Magnetic Resonance (NMR) Spectroscopy
Visit the NMR homepage 
Nuclear Magnetic Resonance (NMR) is a powerful technique for high resolution studies of structure and dynamics in proteins and nucleic acids. NMR facilities available to members of BIG are currently located in the NMR Centre in Room 305 of the MacNaughton Building. They comprise two state-of-the-art Bruker spectrometers. The first is a 500 MHz wide bore solid-state NMR spectrometer with 4 mm triple resonance probe capable of magic angle spinning (MAS) experiments at spinning frequencies up to 15 kHz. BIG members use it for membrane biophysics studies, and for protein structure determination. The second instrument is a 600 MHz narrow bore spectrometer capable of both solution and solids NMR experiments. The variety of solution probes available permit studies of large biomolecules with high sensitivity, using 3D NMR correlation experiments. A high-resolution MAS probe is available for studies of small quantities of solid or liquid samples. The 600 MHz spectrometer is equipped with high power amplifiers and 3.2 mm HCN triple resonance MAS probe for solid-state NMR studies. Its primary use is for structural studies of membrane proteins and insoluble peptide and protein aggregates.
In addition to these existing spectrometers, CFI funding has been obtained to purchase a new 800 MHz solid-state NMR spectrometer. It will be equipped with accessories enabling the most advanced applications of biological solid-state NMR. This instrument will be located in the Advanced Analysis Centre (AAC) of the Science Complex, and will be available to BIG faculty and graduate students.
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Protein Crystallography
X-ray Crystallography (three-dimensional structure of macromolecules)
Much of our knowledge of the architecture of molecules has been determined from studies of the diffraction of X-rays by crystals. This method was first used by W.L. Bragg in 1913. X-ray crystallography allows for the determination of the 3-D structure of both small and large molecules, which is fundamental to understanding how macromolecules such as proteins function. It also allows for the rational design of novel compounds and the interactions with proteins, as might occur in the development of new antibiotics. Crystal structures of proteins such as digestive enzymes, ribosomal proteins, bacterial virulence factors and toxins, hormones, and receptors are essential to understand important physiological processes and also to understand and treat diseases caused by microorganisms. Recent antiviral drugs against AIDS are enzyme inhibitors, and their design was based on the detailed protein-drug interactions provided by crystal structures of the enzymes with the drugs, based on structure-activity relationships. A study of the molecular details of proteins and protein-protein complexes are part of the strategy for the design of antibiotics and other drugs, and major pharmaceutical companies are presently using this approach to determine the structure of proteins with and without bound drug candidates. The new X-ray laboratory that was funded by the Canada Foundation for Innovation is housed in the Science Complex, and will provide University of Guelph researchers with the tools to prepare and test protein crystals for high-resolution structure determination.
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