Undergraduate Research Program

2012-13 WRF Fellows

Evan Boyle - Microbiology & Biochemistry

Evan Boyle examining microscope slideLong fascinated by the often subtle distinction between healthy and diseased conditions, I joined the Gelb Lab in the summer following my freshman year, where I genotyped multiple transgenic mouse lines and expressed recombinant enzymes in E. coli and Sf9 cells to study the role of secreted phospholipases A2 in asthma and other conditions. Being exposed to the immensity of what remains unknown in the field of biomedical research motivated me to explore the emergent technologies of genomic profiling, which led me to the lab of Jay Shendure in the fall of my junior year.

My time in the Shendure Lab has been unimaginably instructive thanks to the remarkable dedication and industriousness of its lab members. Recent advances in information technology and microfluidics have enabled the pursuit of new research questions that would have been deemed inconceivable only ten years prior. In the Shendure Lab, the depth and complexity of the data sets being generated on a daily basis have convinced me that solving the hitherto intractable mysteries that have plagued the field of medicine will require leveraging the increasingly sophisticated computational tools being developed at the UW and other universities worldwide — and I am determined to do my part.

My time spent on undergraduate research has been an invaluable experience, allowing me to meet many extraordinary people here at the UW and fuelling my desire to pursue graduate school; for this reason, I deeply appreciate the support of the Washington Research Foundation.

Mentor: Jay Shendure, Genome Sciences

Project Title: Methods & Algorithms Development for Rapid, Ultra-Low-Cost, Targeted DNA Sequencing

Abstract: New theories accounting for the unexplained heritability of complex diseases posit the existence of rare alleles of large effect size that have escaped detection by genome-wide association studies. Unfortunately, whole genome sequencing remains prohibitively expensive to be used for routine rare variant detection due to the large sample sizes and volume of sequencing necessary to achieve statistical significance. Previous work has shown success overcoming this hurdle through the use of Molecular Inversion Probe technology to test candidate genes in a highly targeted manner, which allows the genotyping of hundreds of individuals for a fraction of the cost. However, the same studies demonstrate that variation in Molecular Inversion Probe capture efficiency leads to severe non-uniformity across interrogated sites, which ultimately manifests in the form of incomplete data sets. To ameliorate this non-uniformity, we seek to validate a new probe selection methodology derived from analysis of a new molecular inversion probe sequencing run targeting random, unbiased regions of the genome. By building a statistical model derived from large, independent capture reactions, we will identify new features of molecular inversion probes that correlate with capture efficiency. Incorporating these features into the probe design will improve in silico predictions of molecular inversion probe capture efficiencies and by extension achieve more acceptable levels of uniformity across targeted sites.

Rahul Brito - Bioengineering

Rahul Brito in labEver since I came to the University of Washington, I knew I wanted to contribute to the battle against infectious diseases in the developing world. I have been researching in Professor Eric Klavins’ Synthetic Biology/Self Organizing Systems laboratory since fall quarter of my sophomore year, and now have the opportunity to do just that, as my project is to build a prototype, ultra-sensitive detector in E. coli that could one day revolutionize the way we diagnose disease in low-resource settings. This project allows me to apply the genome engineering skills I have developed over the last two years while becoming engaged on a much more individual and personal level than ever before on a project with exciting implications. Furthermore, I receive incredible support and mentorship from my lab, which has allowed me to grow into the bioengineer I am today.

After college, I will work in the industry to continue to engineer diagnostics for infectious diseases. I anticipate augmenting this experience with graduate school training in my future. I want to extend my sincere thanks to the Washington Research Foundation for their generous support, which will enable me to continue to throw all my efforts into my research and professional enrichment.

Mentor: Eric Klavins, Electrical Engineering

Project Title: An ultra-sensitive biomolecular detector for low-cost diagnostics

Abstract: Modern-day diagnostics do not meet the needs of low-resource settings due to: 1) slowness in providing results, 2) dependence on electricity, chemical reagents, and trained clinicians, 3) high cost, and 4) high sensitivity threshold. The result is frequent improper diagnosis or false negatives, which can increase the rate of evolution of drug resistance and the rate of patient mortality. There is therefore a pressing need for diagnostics that are inexpensive, rapid, and accurate. The field of synthetic biology holds much promise in this area due to the ease of genomic re-engineering and inexpensive cost of replicating single-cell organism like E. coli and Saccharomyces cerevisiae. As many genomic architectures can function as detectors, a prototype detector will be engineered in E. coli in three phases. First, candidate architectures will be modeled in silico to explore their response over a wide parameter space. Second, these architectures will be constructed and characterized in vivo to determine sensitivity, time to produce output, and ease of output readability. Each detection architecture will be a co-culture, with each strain sensing a specific input molecule. Finally, these detection architectures will be combined with growth control and self-destructive altruism mechanisms that will allow the strain that senses its input to outgrow and induce apoptosis in the other strain, therefore amplifying an output signal to one visible with the naked eye. This prototype detector will hold great promise for one day producing a synthetic, multi-strain diagnostic feasible in low-resource settings.

Kenny Chou - Bioengineering & Electrical Engineering

Kenny Chou in labMedical imaging and minimally invasive modalities had always been an interest of mine. Thinking I’d eventually go into medical school, I started my undergraduate career in Bioengineering. After exposure to the biomedical instrumentation and other technology-orientated classes I realized that I’m more interested in the technology aspect of medicine and decided to pursue a second major in Electrical Engineering. I joined the Human Photonics Lab (HPL) in the summer of 2010 for the CRANE Aerospace sponsored Research Experience for Undergraduates (REU). My first project was to code an image processing operation in a parallel-computing language called the Compute Unified Device Architecture (CUDA), and it introduced me to computational-based research, which I begin to love. My current project is also image processing oriented, and involves processing, registration, and reconstruction of 3D Optical Projection Tomography Microscopy (OPTM) images for tissue biopsy inspection. This project aims to open a new field in biopsy and provide new ways to improve pre-cancer screening, especially for the brain, thyroid, and pancreas. The next project on my agenda is to incorporate semiconductor quantum dots to the OPTM specimen to conduct dual-mode (fluorescence and optical) imaging. 3D dual mode imaging allows us to study tissue morphology and the presence of select biomarkers simultaneously, which has the potential to further improve sensitivity and specificity in cancer detection. After graduation, I plan to pursue a PhD in Electrical Engineering with a focus on medical instrumentations before working in that same industry. I am extremely grateful for the generous support from Washington Research Foundation as it allows me to focus on my research and further motivates me to pursue a career in biomedical technologies.

Mentor: Eric Seibel, Mechanical Engineering

Project Title: Dual-Mode 3D Multi-Cellular Imaging with Optical Projection Tomography Microscopy

Abstract: Cancer is the second leading cause of death in the United States. While fine needle aspiration biopsy (FNAB) is a common minimally-invasive method for diagnosing many types of cancer, it is not 100% reliable. It is necessary to make biopsies more accurate, since their results determine subsequent patient treatment and management. Unlike conventional three-dimensional (3D) imaging methods, Optical Projection Tomography Microscopy (OPTM) is a microscopic imaging method that can produce high resolution 3D images of single-cellular specimens stained with hematoxylin and eosin dyes. Since 3D images can present biological structures in their original architecture, it has permitted clinicians to increase the diagnostic accuracy in adenocarcinoma by threefold, compared to its 2D imaging counterparts. OPTM has also been demonstrated to perform dual-mode (fluorescence and absorption) 3D imaging of single cells. Unfortunately, biopsy samples are rarely single, isolated cells. My previous work, supported by the Washington Research Foundation, demonstrated the feasibility of multi-cellular 3D imaging with OPTM. This project aims to extend the functionality of OPTM to perform multi-cellular imaging in dual-mode and to explore entire FNAB samples in 3D. Dual-mode multi-cellular imaging with OPTM has not been accomplished due to the relatively long imaging time, which causes photo-bleaching of organic fluorophores. This project explores a solution by utilizing semiconductor quantum dots as fluorescent tags to probe for the presence of Her2+ breast cancer cells. This has the potential to reduce sampling error, to prevent the need to isolate single cells for imaging, and to detect the presence of specific molecular biomarkers. Combined with structural information obtained in absorption mode imaging, this imaging method can potentially further improve sensitivity and specificity of FNABs. In the future, dual-mode imaging of tissues can contribute to the understanding of cancer growth and development by relating the presence of specific biomarkers directly to its surrounding tissue architecture.

Ben Horst - Biochemistry & Chemistry

Ben Horst working in fume hoodBen is currently a senior and will graduate in the spring with degrees in Chemistry (BS, ACS certified), Biochemistry (BA), and Mathematics (minor) as well as College Honors and Departmental Honors in Chemistry and Biochemistry. He got his first research experience the summer after his freshman year in the lab of Professor Sarah Keller fabricating and analyzing model cellular membranes. With the Keller group he presented work at the Undergraduate Research Symposium, the Northwest ACS Undergraduate Symposium, and the 2012 National Biophysical Society Meeting. The time he spent in the Keller Lab propelled him to take the next step in his research career by joining the group of Professor James Mayer in studying inorganic chemistry, specifically reduction/oxidation and biomimetic inorganic chemistry, and nanoparticles. When Ben first joined the Mayer group, he undertook a project himself without a graduate student or postdoctoral mentor to study a specific type of reduction/oxidation mechanism called a Multiple-Site Concerted Proton Electron Transfer reaction in which a carbon hydrogen bond is cleaved by transferring the proton to a base and the electron to an oxidant. Now he is collaborating on a new project that combines TiO2 nanoparticles and Concerted Proton Electron Transfer to complete a non-trivial two electron, two proton transfer under relatively mild conditions.

When not in the lab, Ben enjoys TAing in the Chemistry department, running, hiking, sports, and music, playing snare drum in the University of Washington Drumline and singing bass in an a cappella choir on campus.

Mentor: James Mayer, Chemistry

Project Title: Model System for Multiple Site Concerted Proton Electron Transfer

Abstract: Reduction/oxidation reactions are crucial for energy transfer in a wide variety of applications such as water oxidation, water remediation, and biological processes. Proton Couple Electron Transfer (PCET) reactions are increasingly recognized as an important class of this type of reaction. As hinted by their name, these reactions involve the transfer of a proton and an electron from a substrate to other molecules. However, PCET reactions can be delineated further into Single Site PCET reactions, where a single reagent acts as both the electron and proton acceptor, and Multiple Site PCET reactions, where different molecules accept either the proton or the electron. This investigation focuses on these specific Multiple Site PCET reactions (MS-PCET) which are generally not well understood, specifically the breaking of a C-H bond. Using a model system consisting of an oxidant (FeIII(bpy)3-), a base (2,2′-bipyridine) and a substrate (9,10-dihydroanthracene), MS-PCET reactivity will be monitored in an attempt to understand the kinetics of the reaction. Different techniques are used to elucidate the progression of the reaction including UV/Visible and 1H NMR spectroscopy, and stopped-flow injection. The rate of reaction is dependent on each of the reaction components, as well as solvent, temperature, and the surrounding atmosphere. Kinetic analysis of the reaction will eliminate other proton electron transfer reactions and show that the Multiple Site PCET is the singular, plausible mechanism. These reactions will help to establish an understanding of MS-PCET reactions which are crucial to so many biological systems and new technologies such as fuel cells and solar energy.

Averi Kitsch - Bioengineering

Averi Kitsch working at computerI began working in Dr. Colin Studholme’s lab the summer after my freshman year and am proud to be part of a research group whose members have now become both my mentors and friends. The Studholme lab develops and applies new computational and mathematical techniques to study and map brain structure and function. I am currently exploring the relationship between early brain folding and later measures of cognitive, language, motor, and social-emotional developmental outcomes. My research is enriching my education with real life experiences and gives me the opportunity to present my own ideas and pathways. It is ultimately the driving force behind reaching my goals of attending medical school and specializing in neonatology. The support provided by the Washington Research Foundation will help me continue my research and bring me one step closer to accomplishing my goals.

Mentor: Colin Studholme, Bioengineering & Pediatrics

Project Title: Early cortical biomarkers of childhood neurocognitive abilities after premature birth

Abstract: The frequency of premature birth has risen to almost one in every eight births. Although most preterm infants survive, there is growing evidence of adverse neurodevelopmental outcomes due to alterations in brain structure and function. However, the relationship between morphometric changes and final neurological outcome is unknown. This project aims to locate specific structural bio-markers of delayed or decreased brain folding that correlate with decreased neurocognitive abilities, by implementing different quantifications of gyrification. Gyrification, or curvature of the brain, has been identified as a promising structural marker for neurodevelopment. Curvature measurements are heavily dependent on size of the surface which drastically increases during this brief developmental time period; therefore our framework includes normalization and ratio based measures for improved consistency. Our image analysis framework proposes a novel atlas-based automatic tissue segmentation which utilizes age-specific tissue probability maps to serve as a source of spatial priors. We propose to adapt an atlas-based segmentation technique from fetal to preterm analysis with the addition of lobe segmentations that increase the precision of segmentation and registration. This will allow for brain surface extraction by tessellation of tissue maps to reconstruct topology correct representations of the inner and outer cortical surfaces, in which our unique vertex-wise gyrification analysis will be mapped onto a population-average surface by volumetric unbiased template-free groupwise registration. Statistical modeling will be performed for each vertex to detect local and regional patterns of folding and asymmetry. This project has the opportunity to directly relate these measures of early brain folding against later measures of developmental outcomes derived from the Bayley’s Scale of Infant Development (BSID) with the goal of predicting neurocognitive outcomes. Achieving this goal will allow for the possibility of earlier clinical diagnostics permitting timely neurodevelopmental interventions.

Natalie Larson - Materials Science & Engineering

Natalie Larson working in labMy first research experience at the University of Washington was in the Automobili Lamborghini Advanced Composite Structures Lab in the Aeronautics and Astronautics Department the summer before my freshman year. It was during this experience that I realized how much I loved working with carbon-fiber composites, particularly when I got to break them to determine their mechanical properties! While working in the Lamborghini Lab, I discovered my passion for materials science and engineering as I continually found myself excited to learn about how the fibers and matrix work together to create lightweight yet stiff composite structures.

The following year, I joined the Flinn Research Group and have been working in their lab ever since. During my sophomore year, I joined Gary Weber (graduate student) in working on Interpenetrating Polymer Networks as adhesives for advanced composite structures. Such adhesives are intended to improve composite structures fabrication and engineering in aerospace applications. For my second research project, I joined Ryan Toivola (graduate student) in investigating fluorescent probe-functionalized epoxy for use in non-destructive inspection of barely visible impact damage in aerospace composite parts. My independent role in this ongoing research is to characterize the effect of the epoxy’s elastic modulus on the response of the fluorescent probe to damage. I am very excited to be working on this fluorescent probe research, as it has the potential to allow in-situ structural health monitoring of composite aircraft.

I am grateful for my opportunities to conduct research in the Lamborghini Lab and the Flinn Lab, as they have helped prepare me for my future research endeavors in sustainable engineering in graduate school and beyond. I have had the opportunity to meet with leading scientists in composites engineering through this research and through the national SAMPE (Society for the Advancement of Material and Process Engineering) Conferences I have attended for the past two years. Most recently, I had the opportunity to present my research in the Student Poster Session at the National SAMPE Tech Conference in Charleston, SC. This trip was made possible by the support of the Washington Research Foundation. I would like to sincerely thank the Washington Research Foundation for supporting me as I continue with my research with fluorescent probes, as their generosity has and will afford me the opportunity to continue my research as well as present my results at conferences across the nation.

Mentor: Brian Flinn, Materials Science & Engineering

Project Title: Effect of Epoxy Modulus on Activity of a Fluorescent Dye for Aerospace Composite Damage Detection

Abstract: Non-destructive evaluation (NDE) of barely visible impact damage (BVID) in polymer composite aircraft structures is of high importance to the aerospace industry. Impact damage due to tool, bird, or luggage cart collisions can create defects below the material’s surface, significantly reducing the mechanical performance. Such damage, termed BVID, forces engineers to over-design for BVID, adding significant weight to the aircraft. This over-designing is augmented by limitations in NDE, which currently force prohibitive aircraft downtime. The proposed research aims to develop a novel technique for quick, accurate, and cost-effective NDE of BVID during routine aircraft service, potentially allowing composites engineers to design lighter-weight airplane parts. The proposed NDE technique will integrate stimuli-dependent fluorescent dye molecules into epoxy aircraft coatings/matrices, utilizing fluorescence imaging technology. Under stress, the fluorescence behavior of the functionalized epoxy will change, allowing damaged regions of the composite to be located using a spectrometer. Currently, the research is focused on exploring the effects of integrating the fluorescent dye into epoxy systems, and understanding how fluorescence behavior is affected by the local conditions of the epoxy polymer surrounding the dye. As a part of this larger NDE development, the proposed research will focus on determining the effect of the epoxy’s elastic modulus on the fluorescence behavior of the dye. Such research will help determine whether the dye should be incorporated into the matrix, coatings, or topcoats on the aircraft and may reveal the molecular mechanism of dye fluorescence. The proposed research consists of changing the modulus of epoxy with fillers and diluents, measuring the modulus of the epoxy, fabricating functionalized epoxy samples and measuring the fluorescence behavior of the dye under a range of mechanical stresses and local epoxy moduli. Results from this experiment will contribute to study in the fields of molecular engineering, composites, and NDE.

Marvin Nayan - Neurology & Biochemistry

Marvin Nayan in labMarvin Nayan is a senior studying Neurobiology and Biochemistry. He began his research career as a freshman by joining the laboratory of Dr. Jay Parrish at the Department of Biology. Marvin’s project investigates the genetic factors of dendrite patterning and maintenance morphology in fruit fly sensory neurons. He aims to characterize mutations in genes that affect dendrite morphology and gain insight on how the normal version of the gene contributes to normal dendrite patterning. Given that defects in dendrite patterning have been observed in diseases of cognition and in normal aging, he his hopeful this research will contribute to our understanding of genetic mechanisms underlying the maintenance of neuronal function.

As a result of Marvin’s passion for research, his undergraduate career highlights include the Presidential Scholarship, HHMI Integrative Research Internship, and Levinson Emerging Scholar Program. After graduation, Marvin intends to pursue graduate study as part of a medical-scientist training program. His career goal is to perform clinically driven basic science research, with a focus on the cell biology of neurodevelopmental and neurodegenerative diseases. In addition, Marvin hopes to serve as a mentor and role model for underrepresented and disadvantaged students interested in STEM fields.

Marvin’s passion for research derives from the enormous support he receives from his family and friends, as well as from the exceptional mentorship of Dr. Parrish. Marvin is especially grateful for the support provided by the Washington Research Foundation Fellowship by allowing him to conduct highly
independent research, which will help jumpstart his career goal of dedicating his life to biomedical research.

Mentor: Jay Parrish, Biology

Project Title: Analyzing Genetic Regulators of Dendrite Maintenance in Drosophila

Abstract: The neuron is a highly branched and morphologically diverse cell type that constitutes the basic unit of the nervous system. Neurons form complex neural networks with each other through protrusions called axons and dendrites. Different types of neurons often have unique, type-specific dendrite morphologies and the patterning of dendrites influences neuronal function. Although many genes play a role in mediating dendrite patterning, the precise molecular mechanisms in which neurons accomplish their exquisite morphology is poorly understood. Underscoring the importance of dendrite morphology to neuronal function, defects in dendrite patterning likely contribute to numerous neurological disease states and the cognitive decline that accompanies normal aging. To determine which genes are involved in dendrite patterning, we previously identified several gene mutations that affect class IV dendritic arborization (da) neurons in Drosophila larvae. Here, we propose the comprehensive analysis of a novel mutant, mn29. Using live cell imaging and quantitative analysis, we found that mn29 leads to exuberant dendrite branching and intermingling of dendrites in sensory neurons. This latter defect is of particular interest since “self-avoidance” may represent a general mechanism for organizing sensory dendrites and little is known about the genetic basis for this phenomenon. Using time-lapse microscopy, we found that mn29 causes progressive dendrite defects: the dendrite patterning of mn29 mutants is indistinguishable from wild type early in development, but becomes abnormal later in development. Likewise, dendrite defects in many neurological disorders are progressive; therefore further analysis of mn29 may contribute to our understanding of how dendrite maintenance is deregulated in diseased states. Currently, we are working towards identifying the gene affected in mn29 mutants and determining whether mn29 affects dendrite patterning in other functional classes of sensory neurons.

Derek Nhan - Neurobiology & Biochemistry

Derek Nhan working in fume hoodDerek Nhan’s interest in therapies for neurological diseases began as a freshman in a neurobiology course and has flourished while performing research under the mentorship of Dr. Kyra Becker in the Department of Neurology. He has been intrigued with the opportunity to explore a novel research question and design targeted experiments that have the impact of improving clinical treatments for patients with medical disorders. In the Becker Lab, he has been involved in several projects associated with the consequences of post-stroke cerebrovascular damage and his most recent project focuses on the morphologies of neuronal damage as a marker for worse clinical outcome. With support from the WRF Fellowship, he hopes to develop a functional animal model to characterize post-stroke outcome at a cellular and behavioral level. Following graduation, Derek intends to pursue a career in biomedical research combining developments at the bench with the opportunity to deliver them to patients.

Mentor: Kyra Becker, Neurology

Project Title: Central Demyelination Following Ischemic Stroke in an Animal Model

Abstract: Over 800,000 Americans suffer a stroke each year, making this neurological disease the leading cause of long-term adult disability in the United States. An ischemic stroke occurs when blood flow to the brain is interrupted, resulting in inadequate oxygen delivery to brain cells. White matter, largely the myelin sheaths around axons, represents a prominent target of such hypoxic-ischemic injuries and effective interventions given post-stroke are sorely needed. This interaction becomes particularly exasperated in stroke patients due to the breakdown of the blood-brain barrier allowing for interactions between once-segregated central nervous system antigens and lymphocytes from the body. My project investigates the interactions between the autoimmune antigen, myelin basic protein- critical for the development of myelin- and its inflammatory effects on the central nervous system as a predictor of motor dysfunction in an animal model. We induced a stroke in Lewis rats using middle cerebral arterial occlusion and injected them with either lipopolysaccharhide, previously shown to elicit an immune response, or saline for control. I performed a battery of behavioral tests, including the standard neurological score and rotarod a week prior to induction of the stroke and for two and four weeks after. Using immunohistochemistry and luxol fast blue staining, the brains were labeled and a quantitative analysis of myelin coverage between the infracted and the non-infarcted hemispheres were performed using a semi-automated system called Metamorph. Preliminary data has shown demyelination present especially in the caudate-putamen region responsible for regulating movements and often associated with various types of learning behaviors. Additionally, we have observed a correlation between increased myelin loss and reduced motor function immediately post-stroke though further results are pending. These data are critical for developing an animal model for demyelination following ischemic stroke, necessary for characterization of myelin damage as a robust neural marker for mediating worse clinical outcome.

Dan Scott - Earth & Space Sciences

Dan Scott standing in a stream in the fieldI have been hiking and climbing in the Central Cascades my entire life. Though the evolution of the mountains always interested me, I never had the knowledge to critically think about how landscapes came to be until I began studying geology in my sophomore year. I quickly developed a strong curiosity for geomorphology. Through extensive hiking and exploration in the Cascades, I found myself most interested in streams, particularly the high gradient streams that shape the mountain landscapes I love.

I began my current project after talking to Dr. Dave Montgomery. With Dr. Montgomery’s assistance, I was able to focus my broad curiosities into specific, field-oriented research into the nature of high gradient streams. My project aims to better understand the morphologic controls on high gradient streams. I hope to advance the understanding of both hydraulics and controls on bed morphology in step-pool streams, in order to better describe how such streams evolve.

My research experience has hugely influenced my undergraduate career. I believe it has made me a much more capable student, as it has helped me to think more critically about my studies. I am planning on attending graduate school next year, and I think my past research experience, particularly in dealing with the difficulties of designing and refining a project over time, has prepared me very well for graduate research.

I am very grateful to the Washington Research Foundation Fellowship for their support of my research. Because of the fellowship, I will be able to attend the American Geophysical Union Fall Conference this year in San Francisco and hopefully present my work at a major conference this Spring.

Mentor: David Montgomery, Earth & Space Sciences

Project Title: Controls on Channel Form and Sediment Sorting of High Gradient Streams

Abstract: Streams are characterized on a coarse scale by their channel form, and on a fine scale by how sediment is sorted on their beds, though the exact controls on these characteristics in high gradient streams are not fully understood. I seek to quantitatively examine the controls on these two characteristics in high gradient streams. Preliminary field observations have shown a correlation between channel confinement and channel form, though previous research has shown that woody debris also has a significant effect on channel form. I will conduct field surveys to measure woody debris and channel confinement to determine how each one affects channel form. To better understand controls on sediment sorting, I will examine how lithology affects sediment supply by comparing the results of lithologic surveys on two streams in the Cascades that are very similar in most respects except for their lithology. I will use step pools, a characteristic bedform of high gradient streams, to examine how sediment supply and stream power affect sediment sorting on the bed. I will compare pebble counts done in step pools of 7 streams in the Cascades to determine how lithology and stream power affect bed morphology. By quantifying both fine and coarse scale controls on high gradient stream morphology, I hope to move towards more rigorous modeling of high gradient channel evolution as well as better understand how habitat is distributed in a high gradient stream, as habitat location is strongly dependent on sediment sorting.

Bryn Smith - Microbiology

Bryn Smith working at microscopeI have always had a love for science and knew it would be my focus at UW. As I progressed through the prerequisite science classes, I realized my interest in science lies in the specific processes that play into the larger system. It was my sophomore year, and in addition to declaring a major in Microbiology, I was hired as an undergraduate research assistant in Dr. Carol Miao’s lab at Seattle Children’s Research Institute. Dr. Miao’s lab focuses on increasing the efficiency of Hemophilia treatments via gene therapy and immunomodulation techniques. The immunology side of the lab’s research ties into my interests well – it delves into specific pathways in the immune system, but still focuses on the larger picture of treating patients affected by the condition.

I have been lucky to receive outstanding training and guidance in working with mouse models and immunology lab techniques to answer questions in immunomodulation. Now, as a senior, I am working on my own project in the lab utilizing these techniques. Being a part of the Miao lab has also exposed me to different areas of research, such as gene therapy, and has given me a more complete idea of the work that goes into discovering new treatments for diseases. In the future, I plan to pursue a PhD in Immunology or a related biomedical science. I am extremely thankful for the support of the Washington Research Foundation and the dedication they have to encouraging scientific discovery.

Mentor: Carol H. Miao, Pediatrics

Project Title: In vitro expansion of factor VIII-specific T regulatory cells

Abstract: Hemophilia A patients have a deficiency of factor VIII, a protein necessary for the formation of blood clots. Treatment usually involves infusions of replacement clotting factor, but about one-third of patients develop inhibitors to the clotting factor, resulting in reduced efficacy of the infusion. Inhibitors can develop at any time and greatly increase the cost of treatment. T regulatory (Treg) cells have been well characterized in their role of reducing an immune response to an antigen. Additionally, their proliferation in vivo in response to treatment with IL-2 has been studied previously in the Hemophilia A mouse model by the Miao lab. This research project aims to expand factor VIII-specific CD4+CD25+ Treg cells in vitro by costimulation with anti-CD3 and anti-Crry, accompanied by IL-2 treatment. The desired result is an increased number of Tregs that maintain Foxp3 expression and suppressive ability in order to have the same functionality as naturally derived Tregs. Expansion of these antigen-specific cells has implications for further experiments in the adoptive transfer to naive Hemophilia A mice in order to limit the development of inhibitor titers and increase efficacy of factor VIII treatment. This method of treatment has translational potential for treating human patients with hemophilia for long-term results.

Matthew Sonnett - Biochemistry

Matthew Sonnett sitting in front of fume hoodI originally came to UW with the long-term goal of pursuing a Ph.D. in neuroscience, but for reasons I don’t really understand, I figured chemistry was close enough, and I began doing research in Dr. Michael Gelb’s lab during my freshman year that consisted mostly of organic synthesis. Since then, I have remained in the Gelb lab, and I have continued to make small molecule inhibitors that can be used to better understand the role of several proteins intimately involved in a number of inflammatory events. I had not taken organic chemistry when I began working in lab, so my appreciation and understanding of my research, and chemistry in general, grew exponentially over my sophomore year, and continued to blossom last year as I took the graduate organic chemistry series. I cannot overstate how phenomenal of an experience I have had with undergraduate research. It has defined my career ambitions, and it has taught me how to think critically. I am incredibly grateful for the experience that I have had in Dr. Gelb’s lab here at UW, and I would like to thank the Washington Research Foundation for their generous support.

I am applying to Ph.D. programs this fall and I hope to join a lab that is working at the interface of chemistry and biology. I am interested in both enzymology and protein engineering, and I am hoping that my graduate work will be centered in those areas.

Mentor: Michael Gelb, Chemistry

Project Title: Design and Synthesis of Specific Inhibitors for Cytosolic Phospholipase A2 alpha and zeta

Abstract: It is well known that mammals contain several types of phospholipase A2. The cytosolic phospholipases A2 (cPLA2s) are one type, and are composed of six enzymes. There has been significant interest in the cPLA2alpha isoform because of the enzyme’s ten-fold preference for the hydrolysis at the sn-2 position of the glycerol backbone in phospholipids, resulting in the liberation of arachidonic acid (AA). AA serves as a precursor for several highly regulated inflammatory mediators that play an important role in asthma, atherosclerosis, arthritis, and other inflammatory diseases. To address these problems, inhibitors that target cPLA2alpha have been developed by Wyeth pharmaceuticals to serve as anti-inflammatory therapeutics. However, a recent study has shown that in cPLA2 -/- stimulated lung fibroblasts AA production is lessened but still present. cPLA2zeta has been identified as the other enzyme involved in the release of AA. Consequently, our aim is to develop a selective and potent inhibitor that can distinguish between the cPLA2alpha and cPLA2zeta isoforms. Our synthetic strategy is to modify the scaffold of Wyeth’s cPLA2alpha inhibitor. After analyzing structure-activity relationships, we have generated and assayed over two dozen inhibitors, with many more in progress. Our main focus is to increase the selectivity of our inhibitors in order to regulate and better understand the roles of cPLA2alpha and cPLA2zeta in eicosanoid generation.

Sasha Zhdanova - Physics

Sasha Zhdanova working in labI was born on the steppes of Russia, seventeen years ago. I knew that the only way out of Russia was to study science, and to study it well.

Three years ago, I arrived at the UW as a fresh-faced youngling eager to fulfill my newborn promise. Physics was the most daunting and consequently the most rewarding of my subjects, and so I decided to do it until it got boring. The turning point from “not boring” to “complete devotion” came when I began to work for the Eot-Wash lab (otherwise known as the Gravity Group) in the Fall of 2011. For the last year, I worked on improving and adding to the sensor network that controls the conditions of the lab – constant conditions are important for a lab that does precise measurements of gravity.

I am currently building an autocollimator-type device that takes advantage of weak-value amplification to make ultra-precise (on the order of 10 picoradians) angle measurements. I sincerely thank the Washington Research Foundation for supporting this research, and I look forward to the future!

Mentor: Jens Gundlach, Physics

Project Title: Building an Interferometric Quasi-Autocollimator

Abstract: Pre and post-selection offer a wide variety of research developments, particularly in the area of quantum weak-value measurements. The so-called “weak” measurements provide a way of measuring and hence amplifying the state of a large number of particles; taken in the context of angle measurement, the smallest angular disturbances can be magnified and measured. We propose to build a device that uses the concept of weak-value amplification in a modified Sagnac interferometer to measure angles up to the precision of a picoradian. This instrument will be referred to as a interferometric quasi-autocollimator, or iQuAC for short. A proof-of-concept iQuAC has already been built, but its frequency range is severely limited to be between 10 and 200 Hz, and it was built as a prototype on an optical breadboard. We hope to substantially expand the frequency range and build a stable, working iQuAC that will improve on the old one as much as possible. Achieving this is more than possible; there are many, many ways to reduce noise sources, such as increasing thermal conductivity and reducing the effects of optical resonance. A fully-functioning iQuAC that is precise at both high and low frequencies provides a reliable way to measure angles at a distance – a concept that is useful in a variety of fields, such as vibration analysis of very stiff structures or inertial navigational systems.