Biomedical Discussion Group

July 14, 2022

"Forgoing animal experiments: a case study in intervertebral disc regenerative medicine"

Dr. Catherine Le Visage, University of Nantes
Co-Director of Regenerative Medicine and Skeleton (RMeS)
Research Director INSERM (DR2) / Deputy Head Inserm U1229 (RMeS)
Keywords: Low back pain, Disc degenerative disease, Regenerative medicine, Stem cells, Progenitor cells, Biomaterials, chemokines, Growth factors, miRNA, Drug delivery systems, Hydrogel and joint microenvironment, cartilage and intervertebral disc regeneration.

January 25, 2022

"Biomedical Discussion Group: Prevalent chronic illness in Vascular Surgery and the unmet clinical needs"

Dr. Jackie Ho, MBBS, FRCS, FHKAM
Associate Professor (Surgery) Jackie Ho is a Senior Consultant Vascular and Endovascular Surgeon with the Department of Cardiac, Thoracic & Vascular Surgery in National University Health System NUHS. She is also the Director Endovascular Therapy of Vascular Surgery Division.
Keywords: hemodialysis access, limb salvage, peripheral arterial disease, hemodialysis revascularization, chronic wounds, diabetic foot ulcer prevention, angiogenesis and atherogenesis.

January 17, 2018
"Microscale tissue-on-chip technologies: watching biology in high-definition"
Dr. Christopher Moraes, Canada Research Chair in Advanced Cellular Microenvironments; Assistant Professor, Dept. of Chemical Engineering; Associate member, Dept. of Biomedical Engineering; Goodman Cancer Research Center, McGill University [POSTER]
Keywords: tissue, cellular microenvironment, microengineering technology, therapeutics, imaging, mechaniobiology, drug discovery, next generation screening platforms, biomaterials​

January 18, 2018
"Non-invasive fall detection using 3D Deep Convolutional Autoencoder"
Dr. Sheroz Khan, Post-doctoral researcher at the Intelligent Assistive Technology and Systems Lab, University of Toronto [POSTER]
Keywords: fall detection, non-invasive, machine learning, autoencoders, thermal cameras, depth cameras, aging, health informatics, assistive technologies

February 9, 2018
"Spontaneous brain activity and stimuli interaction Non-additive rest-stimulus interaction and mental functions"
Dr. Georg Northoff, MD, PhD, FRCPC Canada Research Chair in Mind, Brain Imaging and Neuroethics ELJB-CIHR Michael Smith Chair in Neurosci and Mental Health Research Unit Director The Royal’s Institute of Mental Health Research, University of Ottawa [POSTER]
Keywords: neuroethics, neuroscience, neuro-philosophy, brain computer interface, rest-stimulus interaction, imaging, consciousness, therapeutic tools for depression and schizophrenia

February 15, 2018
"Ballistocardiography - An Old Methodology in the New IoT Health Monitoring Space"
Dr. Abdul Qadir Javaid, Post-doctoral scholar in Intelligent Systems and Assistive Technology laboratory at University of Toronto and AGE-WELL [POSTER]
Keywords: Ballistocardiography, cardiology, zero-effort monitoring, internet of things, smart textile sensors, machine learning, biosignals

March 2,2018
"Microtechnologies for modelling and monitoring biomechanical cell and tissue systems"
Dr. Craig Simmons, Professor, Mechanical Engineering, University of Toronto Distinguished Professor of Mechanobiology [POSTER]
€‹Keywords: Biomedical engineering, Applied mechanics and design, cellular mechanobiology, cell, tissue and biomaterial micromechanics; design and application of microdevices that mimic complex physiological environments

March 6, 2018
"High-speed observation system designed for elucidating mechanisms of sonoporation" ​
Dr. Nobuki Kudo, Executive Trustee at the Japan Society of Ultrasonics in Medicine, Associate Professor, Biomedical Engineering, Hokkaido University [POSTER]
Keywords: Sonoporation, biomedical ultrasound, biomedical optics, medical systems, phase contrast, fluorescence techniques, phase contrast microscopy, cell membranes, bubble dynamics, cell adhesion

September 20, 2018
"A Positive Health Approach to Older People with Memory Problems and Their Family Caregivers"
Dr. Yvonne Yueh-Feng Lu, Associate Professor School of Nursing Indiana University [POSTER]
Keywords: caregivers, aptitude, cognitive dysfunction, nurse clinicians, social welfare, dementia

October 23, 2018
"Development of a dedicated head and neck positron emission tomography system"
Dr. Shiva Abbaszadeh, Assistant Professor, University of Illinois at Urbana-Champaign, Department of Nuclear, Plasma, and Radiological Engineering [POSTER]
Keywords: cancer, nuclear medicine, medical imaging technology, radiology, computational problem solving, tomography

December 3, 2018
"Interpretable and Collaborative Deep Learning for Low-level Computer Vision"
Dr. Xin Fan, Professor, Dalian University of Technology, and Dean, International School of DUT-RU Information Science & Engineering [POSTER]
Keywords: machine learning, deep learning, imaging, image processing and analysis, computational geometry

November 16, 2017
"In situ gelling and printable hydrogels for tissue engineering and diagnostics"
Dr. Todd Hoare, Department of Chemical Engineering, McMaster University [Poster ] [Registration]

Keywords: hydrogels, biosensors, biomaterials, tissue engineering, nano scaffolds, smart materials

September 29, 2017
"Endocrine regulation of phosphate homeostasis"
Dr. Mohammed S. Razzaque, MBBS, PhD, Department of Oral Health Policy & Epidemiology, Harvard School of Dental Medicine, Boston, Massachusetts, USA; Department of Pathology, Lake Erie College of Osteopathic Medicine, Erie, PA, USA. [Poster] [Registration]

Keywords: bone health, endocrine, phosphate toxicity, fibrogenesis, molecular and cell biology, renal, collagen, heath shock proteins, fibroblast growth factor, physiology, pathology

August 9, 2017
"Application of Human Factors to Quality Improvement and Patient Safety"
Dr. Patricia Trbovich, Academic Research Lead, UHN and Assistant Professor, U of T at University Health Network and University of Toronto [Poster] [Registration]

Keywords: human factors, healthcare systems, health informatics, health technology, patient safety, quality

March 16, 2017
"Technology and Older Adults: Assisting Activities in the Home. Overview of intelligent systems to support aging-in-place"
Emilie M. D. Jean-Baptiste, Ph.D., Postdoctoral Fellow, Dept. of Occupational Therapy / University of Toronto, Toronto Rehabilitation Institute [Poster] [Registration]

Keywords: dementia, aging, artificial intelligence, Markov Decision Processes, assistive devices

November 17, 2016
"Amyloid as a Biomarker of Alzheimer's Disease in the Retina"
Dr. Melanie Campbell, PhD, Professor Physics and Astronomy, University of Waterloo

Keywords: imaging, biomarker, Alzheimer's disease, amyloid deposits, retinas, non-invasive imaging, optical coherence tomography

August 18, 2016
"Image-based models of solid tumors behavior in diagnosis, treatment, prediction"
Dr. Madjid Soltani, Post Doctoral Fellow, Johns Hopkins University and Director, Computational Medicine Institute (CMI) at KNT University of Technology and Ministry of Health, Iran

Keywords: imaging, tumor image diagnostics, tumor treatment and progression, predictive modeling, therapy planning, mathematical modeling of tumor growth, transport phenomena to biological and physiological systems, drug delivery to solid tumors

April 14, 2016
"Nanostructured based Lab-on-chips for optical and electrical detection"
Dr. Sara Mahshid, Postdoc, Leslie Dan Faculty of Pharmacy, University of Toronto

Keywords: nanostructured electrodes, biomolecules, nanotubues, nanowire structures, dielectrophoretic, sample processing, optical and electrical detection, genetic diagnosis, sensitive pathogen detection.

November 19, 2015
Dr. Thomas Willett, Assistant Professor, Systems Design Engineering
University of Waterloo
"A tissue mechanist found in translation"

October 29, 2015
Dr. Alfred Yu, Associate Professor, Electrical and Computer Engineering
University of Waterloo
"Ultrasound imaging innovations for live monitoring of complex flow dynamics"

August 13, 2015
Dr. J. Herbert Waite, PhD, Professor of Biochemistry
Departments of Molecular Cell & Developmental Biology and Chemistry & Biochemistry, University of California, Santa Barbara (UCSB)
"Mussel Power: Defining the Essentials for Translation to Technology"

June 11, 2015
Wei Zhang and Boxin Zhao; Department of Chemical Engineering, Waterloo Institute for Nanotechnology, Centre for Bioengineering and Biotechnology, University of Waterloo
"Zebra Mussel-inspired Electrically Conductive Polymer Nanofiber"

May 27, 2015
Lisette van Gemert-Pijnen, PhD, Professor at the University of Twente in Persuasive Health Technology; Founder of the first Center for eHealth Research and Disease Management (www.ehealthresearchcenter.nl)

Olga Kulyk, PhD, Assistant Professor at the Persuasive Health Technology Lab, Center for eHealth, University of Twente, Enschede, The Netherlands
"Persuasive Health Technology to Improve Health and Wellbeing"

April 2, 2015
Dirk J. Duncker, PhD, Professor of Experimental Cardiology at Erasmus University, Netherlands
"Exercise Training in Adverse Cardiac Remodeling"

November 27, 2014
Shawn N. Whitehead, PhD, Assistant Professor, Depts. Anatomy and Cell Biology; Clinical Neurological Sciences
Western University
"Imaging Lipids in the Vulnerable Brain"

September 10, 2014
Dr. Yuan Fang, Regulatory Scientist, U.S. Food and Drug Administration (FDA)
"FDA’s role in regulating medical devices: premarket and scientific research programs"

October 25, 2013
Dr. Kaleem Siddiqi, Professor and William Dawson Scholar in the School of Computer Science, McGill University
"Heart Wall Myofibers are Arranged in Minimal Surfaces"

October 24, 2013
Dr. Jennifer Hunter, Assistant Professor, Departments of Ophthalmology, Biomedical Engineering and Center for Visual Science, University of Rochester
"Seeing cells in the living eye: Pushing the limits of high-resolution retinal imaging"

October 24, 2013
Dr. Soo-Ik Chang, Professor of Biochemistry, Chungbuk National University
"High-Throughput Analysis of Protein-Protein Interactions Using Droplet-based Microfluidics"

September 11, 2013
Dr. Douglas R. Seals, Department of Integrative Physiology, University of Colorado
"Translational studies of sodium nitrite supplementation to reverse arterial aging" AND “Healthy ways to delay vascular aging”

April 8, 2013
Dr. Brian Tighe, Aston Biomaterials Unit, Aston University, UK
"Hydration and lubrication - Two important challenges for biomaterials development"

Biomaterials science is producing increasingly sophisticated and successful approaches to bodily repair and regeneration with synthetic materials, much of which stems from the pioneering work of Otto Wichterle. Two generic areas that present challenges to this success are bodily hydration and lubrication processes. The ability to maintain and control hydration is important in many body sites - for example: dermal (skin and wounds), ocular (cornea and conjunctiva) and orthopaedic (connective tissue and intervertebral disc). Perhaps surprisingly, there is much commonality in the biochemical entities involved in maintaining hydration control in these very different tissues. Similarly, bodily lubrication mechanisms have many commonalities in the very diverse areas in which they operate. Although the fluids involved have different properties, the underlying compositions and behaviour show many similarities. Examples of this can be found in lung surfactant, synovial fluid and tears. The application of biomimetic principles to the development of both synthetic analogues of these fluids and clinically useful tissue substitutes, identifies the commonalities that underpin their function and enables a surprising degree of rationalisation in the design process involving biomaterials for various body sites.

March 21, 2013
Dr. Michael Rogers, Dept. of Food Science, Rutgers University, New Jersey
"Engineering self-assembled fibrillar networks using hydroxyalkanoic acids as a foundation for rational design of new architectures in molecular gels"

Behind the ability of certain molecules to spontaneously self-assemble into supramolecular aggregates lies an intricate balance between contrasting parameters including solubility and those that control epitaxial growth. Currently, researchers are faced with a lack of fundamental knowledge pertaining to the molecular characteristics and interactions required for self-assembly in organogels causing researchers to rely on serendipity rather than rational design to discover new classes of gelators. An organogel is a gel with the liquid phase being oil as opposed to a hydrogel, which is a gel that has a liquid phase of water. Low molecular weight organogelators (LMOG) form gels, which are small molecules that assemble into fibers, rods, liquid crystals, micelles or ribbons to immobilize oil. Finally, a self-assembled fibrillar network (SAFiN) is a specific type of LMOG that forms crystalline fibers that entrain liquid oil. One of the most simple and effective organogelators, 12-hydroxyoctadecanoic acid (12HOA), forms self-assembled fibrillar networks (SAFiNs) in a plethora of solvents at critical concentrations as low at 0.2%. These gels are thermal-reversible quasi-solid materials comprised mainly of organic liquids that undergo spontaneous formation into SAFiNs. Numerous practical applications of organogels are being investigated as they pertain to templating reactions, controlled drug release, and structuring edible oils. Here, we will present a series of projects aimed at understanding the contrasting parameters which drive the assembly into elongated aggregates associated with SAFiNs in an attempt to answer the basic question-what drives some molecules to form SAFiNs?

March 7, 2013
Dr. Rohit Karnik, Mechanical Engineering, Massachusetts Institute of Technology
"Nudging cells using molecular interactions: Direct separation and analysis of cells in continuous flow"

Separation and analysis of cells is important in biological research, clinical diagnostics, and therapeutics. However, multiple sample-processing steps present a challenge for the development of low-complexity devices for laboratory or point-of-care applications.

In this talk, I will discuss a new approach that can directly separate, enrich, or analyze cells with minimal or no sample processing requirements. We show that transient cell-surface adhesive molecular interactions can exert forces on the cells that can direct the trajectories of cells flowing through microfluidic devices. This mechanical effect of adhesive molecular interactions can be used to design label-free devices for single-step cell separation and analysis. We have developed two device geometries that use asymmetric molecular patterns or oblique ridges to separate cells that interact with the surface-bound molecules. This effect mimics cell rolling, a physiological phenomenon involved in cell trafficking where molecular bonds are continuously formed and broken as the cell rolls on a surface under the action of hydrodynamic forces. Using this approach, we demonstrate separation of cells with high purity and efficiency in parallel microchannel devices, and direct separation of neutrophils from blood with ultrahigh enrichment over red blood cells. The method can sensitively detect whether neutrophils in blood are activated. We extend this approach to controllably contact mesenchymal stem cells with receptor-coated surfaces to quantify cell adhesion behavior by visualization of their trajectories in a "cell adhesion cytometer". We show that the device can track changes in the cell phenotype, which alters the cell adhesion behavior and impacts how the cells flow in the device. Such devices have potential use for point-of-care diagnostics, isolation of cancer cells, and quality control of stem cells.

January 31, 2013
Dr. Claire Davies, Dept. of Mechanical Engineering, University of Auckland, New Zealand
"Increasing independence: Integrating perception, cognition and physical motor control into therapy strategies"

My primary research goal focuses on increasing independence of people with disabilities. Understanding perceptual, cognitive and physical control can support the development of assistive devices and therapies to best meet a patient's needs. The World Health Organisation has provided the International Classification of Function to better evaluate both functional and participation outcomes. Sensory perception includes vision, haptics and sound. For individuals with visual impairment, devices that capitalise on sound such as the AUDEO (Audification of Ultrasound for Detection of Environmental Obstacles) device are beneficial for avoiding environmental obstacles. For people with physical difficulties, orthoses, prostheses and assistive technology can be developed to minimise the effects. Cognitive issues such as dementia present a more difficult means to integrate engineering into therapy outcomes, but EEG can be used to measure emotive response to certain words and those words can be used in Reminiscence Therapy. Some neurological conditions including Hereditary Spastic Paraparesis and Cerebral Palsy affect all aspects of the motor control feedback loop. We capitalise on biomechanical system modeling to allow for tailored therapies, while also developing devices to provide these therapies.

This talk will discuss the importance of integrating clinical and engineering strategies into the design of assistive devices and the development of conservative therapies.

January 17, 2013
Dr. Filip Van Petegem, Dept. of Biochemistry and Molecular Biology, University of British Columbia
"When calcium signaling goes wrong: structure-function analysis of the Ryanodine Receptor in health and disease"

Ryanodine Receptors (RyRs) are large channels that release Ca2+ from the endoplasmic and sarcoplasmic reticulum. They are involved in numerous physiological events, but are primarily known for their role in muscle contraction. Hundreds of RyR disease mutations can cause cardiac and skeletal muscle disorders. This includes CPVT, a condition that gives rise to triggered cardiac arrhythmias and which often results in sudden cardiac death. Another disorder is malignant hyperthermia, whereby the body temperature can rise to a lethal level during anesthesia. Up to now, detailed descriptions of the mechanisms of the disease have been lacking. Here we focus on a region that seems to be of prime importance in RyR function: the amino-terminal disease hot spot. We built pseudo-atomic models of this hot spot in the closed and open state of the RyR. We found that channel opening coincides with a widening of a cytoplasmic vestibule formed by the N-terminal region. This results in a disruption of an interface that is the target for 20 disease mutations. We also solved crystal structures of several disease mutants that affect domain-domain interfaces. Mutations affecting intrasubunit ionic pairs alter relative domain orientations, and thus couple to surrounding interfaces. Buried disease mutations cause structural changes that also connect to the intersubunit contact area. These results suggest that the intersubunit contact region between N-terminal domains is a prime target for disease mutations, direct or indirect. These mutations weaken the interactions, resulting in facilitated opening of the channel and increased release of Ca2+. We present a model whereby both Ryanodine Receptors and Inositol-1,4,5-trisphosphate Receptors, another class of calcium release channels, are activated by altering domain arrangements in the N-terminal region.

November 15, 2012
Dr. Paul Spagnuolo, Assistant Professor, School of Pharmacy, University of Waterloo
"Exploring the anti-cancer treatment applications of nutraceuticals"

Nutraceuticals are biologically active compounds isolated from food and encompass a wide range of popular products such as dietary and herbal supplements. Cancer patients frequently consume these products without fully understanding their potential effects to disease pathophysiology and treatment efficacy. Our research focuses on defining the role of nutraceuticals in cancer chemotherapy with particular emphasis on the treatment of acute myeloid leukemia (AML), a malignant disease characterized by poor rates of survival and high rates of patient relapse. This presentation will highlight new preliminary research that has identified a nutraceutical, a lipid derived from avocados (termed ALA), as a potent and novel anti-leukemia drug with specific toxicity toward leukemia cells.

Further, we have demonstrated that ALA?s potential mechanism of leukemia cell death is through autophagy, which offers a new and exciting therapeutic strategy for the treatment of AML.

June 21, 2012
Dr. Eric Finot, University of Bourgogne, Dijon, France
"Selectivity and detection limit for protein sensing using localized and propagating surface plasmon"

April 18, 2012
Dr. Richard Epand, Department of Biochemistry & Biomedical Sciences, McMaster University
"Phosphatidylinositol Cycling and Acyl Chain Specificity"

April 11, 2012
Dr. Elise Stanley, Canada Research Chair, Department of Physiology, University of Toronto
"The calcium channel and transmitter release site at the presynaptic nerve terminal"

January 18, 2012
Dr. Howard Dobson, VP Research and Development, CanCog Technologies
"The Dog as a Natural Model of Alzheimer's Disease and Other Age Related Conditions"

November 30, 2011
Dr. Michael Patterson, Department of Medical Physics and Applied Radiation Sciences, McMaster University, Juravinski Cancer Centre
"Quantitative Optical Molecular Imaging in Small Animals"

September 28, 2011
Dr. Evgeny Pavlov, Department of Physiology & Biophysics, Dalhousie University
"Kinetics and molecular mechanisms of the mitochondrial calcium transport."

Mitochondrial calcium transport is critically important for regulation of multiple physiological processes occurring in mammalian cells as well as in cell response to pathological stress. Research in our laboratory in focused on studies of molecular mechanisms responsible for this transport. Specifically we are interested in understanding of the contributions of two biological polymers, inorganic polyphosphate (polyP) and poly-3-hydroxybutyrate (PHB), to this process. In my talk I will review the current state of the field with the focus on recent progress in determination of the molecular identities of mitochondrial calcium transporting systems. I will discuss remaining challenges and controversies, and will also present our own data which suggest that in mammalian mitochondria PHB mediates calcium uptake by the uniporter mechanism whereas polyP is critically important for induction of the calcium-dependent permeability transition pore.

September 21, 2011
Dr. Carolyn Ren, Department of Mechanical & Mechatronics Engineering, University of Waterloo
"Droplet-based Microfluidic Platforms - Enabling Technology for High Throughput Screening and Combinatorial Testing"

Microfluidics is multidisciplinary by nature having fundamental roots in physics, biochemistry and engineering. Microfluidic platforms have been widely applied for chemical, biological and biomedical assays benefiting from their small size which translates to reduced sample reagents, shortened analysis time and high throughput. Most microfluidic platforms are single phase based where either liquid or gas is the carrier fluid though liquid is used much more often. This type of platform suffers slow mixing due to laminar flow nature, low throughput, and contaminations between different liquid streams and between liquid and solid walls which cause low repeatability and reliability.

Droplet-based two-phase microfluidic platform is an excellent alternative which can address these disadvantages. In this type of platform, droplets are encapsulated by another different phase, therefore, contaminations between droplets and between droplets and channel walls are eliminated. In addition, droplets are rotating when transported through the channel network which provides three-dimensional mixing overcoming the slow mixing problem. Most importantly, the throughput of droplet-based microfluidic platforms is magnitude higher than single-phase microfluidic platforms because droplets can be generated at kHz with minimum (1-3 %) variance in their size or volume and each droplet can be treated as one individual reactor. Therefore potentially, droplet-based microfluidic platforms could have kHz throughput provided each droplet can be manipulated as desired.

Both gas-liquid and two immiscible liquids (water and oil) systems have been employed to make liquid droplets in microfluidic platforms.
In this talk, only the system employing two immiscible liquids to generate droplets is discussed. To successfully design and control droplet-based microfluidic platforms, several functions including droplet generation, droplet trafficking and droplet sorting must be understood, which will be the main focus of this talk.

May 11, 2011
Dr. Joanne Nash, Department of Cell & Systems Biology, University of Toronto at Scarborough
“Understanding cellular and molecular changes in synaptic dynamics in the parkinsonian striatum”

Changes in synaptic plasticity within the striatum play a major role in the generation of parkinsonian symptoms, and side effects of L-DOPA, such as dyskinesias. Re-organisation of molecules and proteins that control neurotransmission within striatal synapses probably underpins these abnormalities in synaptic plasticity. Determination of the key synaptic players responsible for driving such abnormalities will reveal novel therapeutic targets for the treatment of parkinsonian symptoms, and also dyskinesias. Using 6-OHDA-lesioned rodent models of Parkinson's disease and dyskinesia in combination with patch clamp electrophysiological recordings, biochemical techniques and genetic manipulation, we have found fundamental changes in synaptic function that may underpin the pathological abnormalities responsible for parkinsonian symptoms and L-DOPA-induced dyskinesias.

April 13, 2011
Dr. Catharine Winstanley, Department of Psychology, University of British Columbia
“Rats, risk and research: What can rats teach us about the neurobiological basis of impulsivity and gambling?”

Impulsivity can be broadly defined as acting or making decisions without appropriate forethought, thereby enhancing the potential for negative consequences. High levels of such impulsive behaviours are associated with psychiatric disorders such as bipolar disorder and ADHD, and impulsivity is increasingly recognised as a risk factor for drug addiction. Using animal models of drug self-administration, and tests of impulsive behaviour adapted from neuropsychology protocols, neuroscientists have shown that highly impulsive rats resemble human drug addicts in how they take cocaine. Furthermore, repeated self-administration of cocaine can likewise enhance impulsivity during withdrawal, suggesting that poor impulse control can contribute to both initial drug-seeking and subsequent relapse. Both neuroimaging and gene expression data highlight important roles for the orbitofrontal cortex and striatal dopamine signalling in these processes. Pathological gambling has recently been described as a behavioural addiction, and high impulsivity has also been observed in this clinical population. Building on the success of behavioural models of drug addiction and impulse control, researchers have begun to develop rodent analogues of gambling-related decision-making in order to investigate the extent to which behavioural and chemical addictions might overlap in terms of their brain circuitry and neurochemical control. Our own data so far suggests that rats' performance in gambling-like tasks resembles that of humans, even with respect to potential cognitive biases or "irrationality". Furthermore, different aspects of gambling-like behaviour can be modulated by serotonergic and dopaminergic drugs, paralleling some clinical findings. These rodent models of gambling processes may therefore provide useful data regarding the neurobiological basis of gambling and putative pharmacotherapies for problem gambling behaviour.

March 30, 2011
Dr. Jennifer Cobb, Department of Biochemistry and Molecular Biology, University of Calgary
“The MRX complex regulates cohesin during replication: In times of stress keep your sister close.”

The Mre11-Rad50-Xrs2 (MRX) complex is important for the maintenance of genomic integrity and is recruited to forks during pauses in replication. Cohesion between sister chromatids is coupled to fork progression and the cohesin complex holds replicated chromosomes together from their synthesis until the onset of anaphase. Upon performing ChIP-Chip analysis we show there is additional cohesin associated with forks when they stall, above levels detected in an unperturbed S phase, and this is dependent on the MRX complex. Moreover, we find the MRX complex is necessary for proper sister chromatid cohesion (SCC), and this function depends on the structural integrity and bridging capacity of Rad50. Taken together, our data suggests one critical role for the MRX complex in preserving chromosome integrity involves supporting the architecture of newly synthesized daughter strands during pauses in replication, preventing fork-associated damage.

February 16, 2011
Dr. Shana Kelley, Director, Division of Biomolecular Sciences, Faculty of Pharmacy, University of Toronto
“Nanostructure-enabled electronic diagnostic devices”

The analysis of panels of molecular biomarkers offers valuable diagnostic and prognostic information for clinical decision making. Robust, practical platforms that detect low levels of biomolecules (< 1000 copies) are urgently needed to advance medical care by diagnosing and predicting the progression of cancer and other disease states. Electrochemical methods providing low cost and direct biomarker read-out have attracted a great deal of attention for this application, but have, to date, failed to provide clinically-relevant sensitivity. We hypothesized that controlled nanostructuring of electrode surfaces could promote surface accessibility and enhance capture rate and efficiency to solve this long-standing problem, and recently showed that the nanoscale morphologies of electrode surfaces control their sensitivities. In addition, we have worked towards integrating nanomaterials-based electrodes into a chip-based platform to facilitate multiplexed analysis in a robust, practical format. Our efforts to use this platform to detect nucleic acid and protein biomarkers in clinical samples to develop tests for infectious disease diagnosis and oncological management will be featured in this lecture.

December 1, 2010
Dr. Joseph Tauskela, Institute for Biological Sciences, National Research Council of Canada
“A framework for pursuing neuroprotection in cerebral ischemia developed from a 'Stroke in a dish' model”

Neuroprotection clinical stroke trials have failed. Major issues remain to be resolved at the preclinical level: (i) timing ('time is brain'), efficacy and adverse effect issues have not been adequately addressed; (ii) lack of prioritization of targets in the neurotoxic signaling cascade induced by ischemia and; (iii) drug discovery programs fail to prioritize among an ever burgeoning number of neuroprotective candidates. Using a stroke-like model in neuron cultures, oxygen-glucose deprivation (OGD), a neuroprotective 'framework' has been developed. First, screening of agents which pre-emptively precondition neurons reveals convergence at a common neurotoxic target, which is to suppress cellular glutamate release during OGD. However, this glutamate release is not prevented during prolonged OGD, representing a 'ceiling' of neuroprotection. Second, administration of an anti-excitotoxic receptor antagonist drug cocktail immediately prior to glutamate release during prolonged OGD preserves neuroprotection. However, prolonging OGD even further results in a second ceiling of neuroprotection, which necessitates a more aggressive anti-excitotoxic drug cocktail. In summary, pre-emptive preconditioning 'buys time' before requiring acute 'rescue' with a drug cocktail. This framework addresses what is required for neuroprotection, but not what may be clinically possible. To gauge if the neuroprotective framework can be tolerated, investigations of spatiotemporal patterns of network activity and functional connectivity are in progress using neurons cultured on multi-electrode arrays.

October 27, 2010
Dr. Aaron Fenster, Robarts Research Institute
“Use of 3D Ultrasound for diagnosis and treatment of human diseases”

The last two decades have witnessed unprecedented developments of new imaging systems making use of 3D visualization. These new technologies have revolutionized diagnostic radiology, as they provide the clinician with information about the interior of the human body never before available. Ultrasound imaging is an important cost-effective technique used routinely in the management of a number of diseases. However, 2D viewing of 3D anatomy, using conventional ultrasound, limits our ability to quantify and visualize the anatomy and guide therapy, because multiple 2D images must be integrated mentally. This practice is inefficient, and leads to variability and incorrect diagnoses. Also, since the 2D ultrasound image represents a thin plane at an arbitrary angle in the body, reproduction of this plane at a later time is difficult.

Over the past 2 decades, investigators have addressed these limitations by developing 3D ultrasound techniques. In this paper we describe our developments of 3D ultrasound imaging instrumentation and techniques. In our approach the conventional ultrasound transducer is scanned electronically, mechanically or using a free-hand technique. The 2D images are digitized and then reconstructed in real-time into a 3D image, which can be viewed and manipulated interactively. We describe the use of 3D ultrasound for diagnosis, image-guided therapy and use in basic biomedical research. Examples will be given for imaging various organs, such as the prostate, carotid arteries, and breast, and for the use in 3D ultrasound-guided brachytherapy and cryosurgery. In addition, we describe 3D segmentation methods that can be used for quantitative analysis of disease progression and regression in humans as well as research animal models.

October 13, 2010
Dr. Kostadinka Bizheva, Department of Physics & Astronomy, University of Waterloo
“Non-invasive optical imaging of the structure and function of biological tissue with Optical Coherence Tomography”

Abnormal development of biological tissue, as well as the early stages of many diseases exhibit structural changes occurring on cellular level, alterations in the local blood flow, and complex changes in the cellular biochemistry. Both biological science and current medical practice call for development of novel, minimally invasive methods capable of detecting these changes. The novel technologies can be used to provide understanding of the origins and the time course of development of different pathologies, as well as to diagnose diseases at early stages when treatment is most effective and irreversible damage can be avoided or postponed. This presentation will introduce a relatively novel non-invasive optical imaging technique, ultrahigh resolution optical coherence tomography (UHROCT), that permits in-vivo cross-sectional visualization of tissue morphology in superficial depths of 1-2 mm in non-transparent biological tissue with micrometer scale resolution. The principles of image formation in UHROCT and the possibility of extracting functional information (spectroscopic and flow measurements) about the imaged object will be reviewed. Current applications of UHROCT in ophthalmology, dermatology, neuroscience and neurosurgery will be discussed.

December 2, 2009
Dr. Russ Tupling, Department of Kinesiology, University of Waterloo
“The Role of Sarcolipin in Thermogenesis, Diet-Induced Obesity and Glucose Intolerance”

Promoting inefficient metabolism in muscle represents a potential treatment for obesity. The long term objective of our research is to understand the factors involved in regulating Ca²⁺ transport efficiency by SERCA pumps and to determine if alterations in Ca²⁺ transport efficiency or the stoichiometry of SERCA pumps can affect metabolic rate and susceptibility to diet-induced obesity and type II diabetes. Skeletal muscle sarcoplasmic reticulum (SR) contains sarcolipin (SLN), a small protein molecule that regulates the activity of SERCA pumps but its physiological role is unclear. We have established through our research using Sln-null mice (SLNKO) that SLN uncouples ATP hydrolysis from Ca²⁺ transport by SERCA pumps thereby reducing their transport efficiency. After going over relevant background on SERCA pump energetics and regulation by SLN, I will present results from our recent high fat feeding experiments investigating whether Sln-null mice are more susceptible than wild type mice to diet-induced obesity and glucose intolerance.

November 4, 2009
Dr. Bo Cui, Department of Electrical and Computer Engineering, University of Waterloo
“Nanoimprint lithography/hot embossing and its application in tissue engineering and bio-sensing”

Similar to CD/DVD duplication process, nanoimprint lithography (NIL) is based on mechanical hot embossing principle onto thermoplastic polymers that become soft when heated. NIL is the choice for high throughput patterning of Nano-structures and devices, because other nano-lithographies like electron beam lithography are too slow for volume production. After an introduction to NIL and nanofabrication techniques, I will go over the following three applications of micro/nano-fabrication that I carried out at NRC -Industrial Materials Institute near Montreal before joining Waterloo last November.

1. Tissue Engineering - guided growth of corneal and cardiac cells. In tissue engineering, if tissue is to be repaired, the new cells must be aligned and positioned correctly. Such alignment can be achieved by culturing the cells on anisotropic topographic features such as a grating pattern.

2. Bio- and chemical sensor based on surface enhanced Raman scattering (SERS). SERS is the phenomena that Raman scattering is enhanced by a factor up to 10^14 when the molecules are adsorbed on a rough metal surface or nano-structured metal islands. SERS substrate fabricated by nano-lithography offers more reproducible performance than metal colloid agglomeration.

3. Bio-sensor based on surface plasmon resonance. Surface plasmon is an evanescent surface electromagnetic wave caused by collective and coherent free electron oscillation at a metal-dielectric interface. Since the resonance frequency is highly sensitive to the refractive index change on the metal surface, it can be employed to detect bio-binding events. By patterning the Au surface with nano-structures, we found an increase in sensitivity by 5 times. The fabrication of sensors based on extraordinary optical transmission through nano-hole array in a Au or Ag film will also be introduced.

October 7, 2009
Dr. Eric Jervis, Department of Chemical Engineering, University of Waterloo
“Research in the Laboratory for Single Cell BioEngineering”

My laboratory applies imaging, cell tracking, informatics, and microenvironment engineering to access and direct transgenerational changes in cell phenotype in culture. There are three ongoing research foci: (i) Long term stem cell imaging and tracking the Canadian NCE in stem cell research funds my laboratory as a core facility to provide cell biologist in the network access to long term live cell imaging facilities and expertise. Single cell analysis forms the basis of this program. Here, individual cells and their progeny can be imaged and tracked over time in culture for several hundred hours. This data set enables the identification of clonal expansion lineage trees and corresponding development of differentiated phenotype. A study on the development of a support niche in human embryonic cell cultures will be presented to illustrate the approach; (ii) Tissue and organ decellularization this program is aimed at formulating processes for the decellularization of cadaveric tissues and organs to provide biomaterials for cell therapy applications. A major challenge in tissue engineering is the provision of a support matrix for transplanted cells that enables immediate integration into the circulatory system following implant. Preliminary work on whole rat heart decellularization will be presented to highlight ongoing challenges with this objective; (iii) Drug delivery and characterization a major activity in my laboratory is analysis of the delivery of drugs to cells in culture. This research integrates mass transport and pharmacodynamics modeling with proteomic analysis of drug action on target stem and progenitor cells. We are currently combining long term live cell imaging, microfluidcs and DIGE proteomic analysis to examine the effects of candidate beta-cell stimulatory drugs on human islet derived progenitors in culture. Results from a recent study performed on culture expanded human islet outgrowth cultures will be presented.

June 3, 2009
Dr. Roderick Slavcev, School of Pharmacy, University of Waterloo
“Exploiting Phage and Phage-encoded Systems for the Design of Novel Therapeutics”

Bacteriophages total approximately 1031 and comprise the greatest repertoire of DNA on earth. As such, these entities contain a virtually limitless supply of extremely valuable information with application to antibacterial design and the exploitation of unique recombination and other genes and systems. In addition, some phages are capable of multivalent expression of peptides or proteins fused to structural capsid or tail components and are genetically easily manipulated, making them suitable for the design of a wide variety of protein and/or gene delivery therapeutics.
Our lab endeavours to take advantage of the tremendous pliability of specific phage to design a variety of new therapeutics that exploit the extended manipulation properties of caudoviridae (tailed) phages­in particular N15. N15 is a temperate phage that is virtually indistinguishable from that of and is thus likely suitable as a phage display vector. However, the genetic organization is vastly different and rather than integrating into the chromosome like its lambdoid cousins, N15 lysogenizes its E. coli host as a linear covalently closed (lcc) “dumbbell-shaped” plasmid. This DNA conformation is solely due to the activity of the phage-encoded TelN recombinase on a minimal 56 bp telRL target site and may provide many advantages over current vector systems. We are working toward the development of a simplified system for the in vivo production of TelN-telRL-mediated lcc miniplasmids that in combination with novel Gemini surfactant, targeted liposome technology (Wettig lab) may yield a highly safe and efficient lipoplexed miniplasmid gene delivery system.

April 1, 2009
Dr. Bruce Reed, Department of Biology, University of Waterloo
“Live Imaging Cell Death in the Drosophila embryo” (25 minutes)

Programmed cell death during animal development most often occurs by caspase dependent apoptosis. The programmed removal of entire tissues during development, however, frequently occurs with evidence of cellular autophagy. While autophagy is familiar as a survival response in stressed or starved cells, a growing body of evidence indicates that autophagy can also promote cell death. Using genetic and live imaging based approaches my lab is investigating the relationship between autophagy and apoptosis in the Drosophila embryo. I will present our model system and techniques for evaluating autophagy and apoptosis. Our results support the view that autophagy is a prerequisite for the activation of caspase-dependent apoptotic death during the elimination of an extra-embryonic tissue in the Drosophila embryo. The relevance of these results to human neurodegenerative disease will be discussed.

Dr. Vivian Choh, School of Optometry, University of Waterloo
“Cellular mechanisms mediating ocular functions and visual conditions” (25 minutes)

Myopia (near-sightedness) is the condition in which eyes are too long for their optics, resulting in distant objects focussing in front of the retina. In most young animals, eye growth is modulated to progressively reduce any refractive error. This process, called emmetropisation, has been exploited to experimentally induce myopia in an effort to determine the mechanisms regulating eye growth. Animal studies in which eyes have been disconnected from the brain show that compensation for visual cues still occurs as in normal eyes, indicating that eye growth is locally regulated, presumably by the retina. However, optic nerve section results in shorter than normal eyes, as well as loss of some cells in the retina. Thus, optic nerve section is used to probe how and which cells of the retina control eye growth in response to visual signals. Studies suggest that subcellular structural proteins within the lens might impart contractile activity to the lens. In addition, mechanical stress has been shown to induce biochemical activity within other cells, yet studies of the cellular changes that affect and are affected by a deforming (mechanically stressed) lens have been neglected. A physiological accommodation model, which allows direct measurement of the lens during nerve-stimulated focussing, is used to investigate how the subcellular structures of the lens are affected by naturally-induced mechanical stress and other growth-related changes to the eye.

March 4, 2009
Dr. Carolyn Ren, Department of Mechanical & Mechatronics Engineering, University of Waterloo
“Microfluidic-based Lab-on-a-Chip Development for Biological and Chemical Analysis” (25 minutes)

Lab-on-a-chip devices (microfluidic chips) have drawn a great deal of attention over the past decade due to their ever-increasing applications in biomedical diagnosis, chemical analysis, and pharmaceutics. Advantages of these devices, which are currently in use for clinical detection, DNA scanning and electrophoretic separation, include increased portability and resolution in addition to reduced cost and analysis time. Typically, a biochip is a thin glass or plastic plate with a network of micro- or nanochannels, sensors, electrodes and detection units integrated on it. The target analytes are transported through microchannels by electroosmotic driven flow and/or pressure driven flow. The development of Lab-on-a-chip devices is multidisciplinary by nature requiring a wide range of expertise from science and engineering. Contributions from engineering fields facilitate the device development and improve the performance of the devices.

The ultimate goal of my research is to develop integrated microfluidic-based Lab-on-a-Chip devices for chemical and biomedical analysis and diagnosis. Three major activities are being conducted at Waterloo Microfluidics Laboratory, which include design and optimization using numerical simulation tools, rapid prototyping using softlithography technology, and characterization using fluorescence-based visualization techniques. Each of these activities will be elaborated in this presentation together with examples of ongoing projects.