2015-16 Levinson Scholars

Logan is currently a senior at the University of Washington studying neurobiology. He became interested in research as a freshman when he joined the Dhaka Lab. Over the course of the past three years he has developed a passion for studying the cellular and molecular mechanisms responsible for pain sensation. In Dr. Dhaka’s lab Logan studies the mechanism responsible for the itching and burning side effects of a topical skin cancer drug using the zebrafish model system. The goal of his research is to characterize the pathway that transduces the sensations associated with this drug, in the hope of contributing knowledge to the current debate about the ways in which itch and pain are differentiated by primary sensory neurons and identifying ways in which the side effects of this drug can be prevented. After graduation Logan plans to take a year to work in a research-setting full time before applying to M.D./Ph.D. programs. Logan would like to thank is mentor Dr. Ajay Dhaka, as well as Kali Esancy and Andrew Curtright, for their guidance over the past few years. Additionally, Logan would like to thank Dr. and Mrs. Levinson for their support of his research and future endeavors.

Mentors: Ajay Dhaka, Biological Structure

Project Title: Do Fish Itch?: Evidence for Itch Caused by Direct TRPA1 Activation

Abstract: Chronic itch is a debilitating condition that plagues millions of people. It is a symptom of many illnesses including cancer, kidney failure, liver cirrhosis, MS, and shingles and is a side effect of some common medications. Using the Zebrafish (Danio rerio) model system, we are exploring whether Zebrafish experience itch as a discrete sensation from pain and the molecular and cellular mechanisms that cause itch sensation. The Zebrafish model system has allowed us to identify previously overlooked components of the somatosensory pathway responsible for the negative sensations produced by Imiquimod, a TLR7 agonist used to treat skin cancer. Contrary to previously published literature that claimed Imiquimod caused itch via TLR7, we have found that TLR7 is not expressed in sensory ganglia, such as the trigeminal ganglion. Additionally, we have observed that Imiquimod has the capacity to directly activate TRPA1, an ion channel that transduces chemical pain and is commonly expressed in sensory ganglia. Based on our data we believe the most likely transduction mechanism of Imiquimod stimuli is intensity coded direct activation of TRPA1. The idea that Imiquimod directly activates TRPA1 seems to suggest that Imiquimod sensation is in fact not itch at all, but pain. However we have documented an itch like behavior in adult zebrafish that have been exposed to Imiquimod. Fish exposed to this drug rub their lips against the walls of their tank for an extended period of time, a discrete behavior from pain, which reduces movement and increases respiration. In combination with our knowledge of how Imiquimod acts directly on TRPA1, these data suggest that Imiquimod may induce itch by intensity coded activation of TRPA1.

Biomolecular systems with global-scale impacts are Ryan’s primary area of interest. His passion attracted him to the lab of Ginger Armbrust to study marine phytoplankton, the key drivers of many biogeochemical processes. Ryan aims to use molecular biology techniques in conjunction with in silico bioinformatics to look ‘under the hood’ at phytoplankton-driven processes. His first project at the Armbrust Lab, in the UW’s Center for Environmental Genomics, used comparative transcriptomics to investigate the evolutionary history and distribution of iron metabolism genes in marine diatoms. Last year, he began a new project to uncover the biochemical pathways involved in CO₂-sensing and response in the model diatom, Thalassiosira pseudonana. He is broadening the scope of the project this year by using RNA sequencing to investigate the global changes in gene regulation underlying these processes. Ryan is majoring in Molecular, Cellular, and Developmental Biology with a minor in Oceanography. After graduation, he’s looking forward to continuing research while working toward a Ph.D. in Biological Oceanography. Outside of academics, Ryan enjoys camping, bicycling and meditation.

Mentors: Virginia Armbrust, Oceanography

Project Title: Regulation of Gene Networks by Cyclic AMP in the Diatom Thalassiosira pseudonana

Abstract: Anthropogenic emissions are projected to double atmospheric concentrations of CO₂ by the end of the century, increasing ocean acidification and fundamentally changing the marine environment. Since diatoms compose ~20% of global primary production, it is important to understand how they respond to variations in CO₂ concentration and regulate carbon assimilation in the face of rising CO₂. In previous work, we identified clusters of co-expressed genes with differential expression under elevated CO₂ in the model diatom Thalassiosira pseudonana. One cluster of genes that were down-regulated under elevated CO₂ encode putative carbon concentrating mechanism (CCM) proteins, which participate in control of carbon assimilation. These genes share an upstream cis-regulatory motif involved in the repression of a CCM gene in Phaeodactylum tricornutum, a distantly related diatom, which uses cyclic AMP (cAMP) as the second messenger. To test whether cAMP plays a similar role in CO₂-responsive gene regulation in T. pseudonana, we grew T. pseudonana under high and low CO₂ conditions and sampled cultures prior to or following exposure to 3-isobutyl-1-methylxanthine (IBMX), which raises intracellular cAMP concentrations. We have submitted total RNA from this experiment for whole transcriptome sequencing. We predict that genes in the CCM cluster will be repressed following IBMX treatment. We also predict cAMP signaling will regulate genes involved in the cellular processes of diel oscillation, cell cycle progression, and silicate metabolism. cAMP signaling plays crucial roles in core cellular processes throughout the tree of life, but its role in diatoms is not well understood. By taking the novel approach of directly manipulating levels of this intracellular messenger, this research will provide mechanistic insights into diatom responses to changing ocean environments and improve our understanding of the evolution of carbon concentrating mechanisms in this group of globally significant phytoplankton.

Emily is a senior majoring in Molecular, Cellular, and Developmental Biology. She joined the Torii Lab during her freshman year, hoping to gain a deeper understanding of the cellular processes underlying plant development and their implications for global climate change. The primary goal of the Torii Lab is to investigate the molecular and genetic processes that control the differentiation of plant epidermal stem cells into stomata. Through her research project, Emily aims to visualize and quantify the behavior of several signaling peptides that mediate this stomatal differentiation pathway. Emily would like to thank her mentor, Dr. Keiko Torii, for her invaluable guidance and for the tremendous opportunity to conduct research in her lab. With the generous support of the Levinson Program, Emily hopes to finalize and publish her findings before graduation and further contribute to our understanding of the relationship between stomatal formation, plant productivity, and drought tolerance. After completing her undergraduate studies, she plans to pursue a Ph.D. in computational biology and a career in genomics research to help advance the field of personalized medicine. Outside of the lab, Emily works as a tutor at the Odegaard Writing and Research Center and spends her free time gardening, cooking, and baking.

Mentors: Keiko Torii, Biology

Project Title: Visualizing and Quantifying Peptide Behavior Specifying Epidermal Patterning in Arabidopsis

Abstract: Stomata, valve-like pores encircled by guard cell pairs on the plant epidermal surface, serve as the primary gateway for gas exchange with the environment as well as water movement through the vasculature in plants. During organ morphogenesis in model organism Arabidopsis thaliana, the differentiation process from an unspecialized protodermal cell to a fully-mature pair of guard cells, in addition to the coordination of proper stomatal spacing and density in the epidermis, is regulated by a complex signaling pathway that involves a series of interactions between positional signaling peptides and transmembrane receptors. My signaling peptide genes of interest, EPIDERMAL PATTERNING FACTOR (EPF) 2, EPF1, and STOMAGEN (also called EPFL9), play major roles in this signaling pathway. Previous studies have looked extensively into the functions and interactions of EPF2, EPF1, and STOMAGEN; however, the effective working distance of these peptides has yet to be determined. Here, I use a Cre-lox Gal4 system to induce site-specific overexpression of my target peptides, in which induced clones are positively indicated by the presence of fluorescent protein. Using this system, I will quantify and characterize the distance over which the secreted signaling peptides EPF2, EPF1, and STOMAGEN can influence stomatal patterning in Arabidopsis.

Darby is an honors candidate in both the computer science and neurobiology departments, as
well as a student in the Computational Neuroscience Training Program. His work focuses on
bridging the divide between computers and the brain. The majority of previous work in this field has focused on extracting information from the brain. A lot of Darby’s work focuses on a
different question: how can brain stimulation be used to encode information into the human
brain? In his current project, he is asking both questions and working to facilitate direct human
brain-to-brain communication. His undergraduate research career has inspired him to pursue a Ph.D. after graduation and continue work on brain-computer interactions. He would like to thank his mentors, Dr. Andrea Stocco and Dr. Rajesh Rao for the opportunities they have provided as well as Dr. and Mrs. Levinson for their generosity.

Mentors: Dr. Andrea Stocco, Psychology and Dr. Rajesh Rao, Computer Science

Project Title: Characterization of TMS-Induced Percepts for Advanced Brain-to-Brain Transmission of Complex Visual Information

Abstract: Phosphenes are temporary visual percepts which can be elicited via transcranial magnetic stimulation (TMS) of the visual cortex. Often described as flashes or blobs of light, phosphenes usually occupy a small subset of the visual field and can be consciously perceived and described by a human subject. In order to investigate the relationship between phosphene
characteristics and the methods in which they are elicited, subjects are asked to draw the phosphenes they perceive in response to different stimulation intensities, locations, and orientations. This information is then used for direct brain-to-brain communication of simple images. Functional magnetic resonance imaging (fMRI) is utilized to decode information from the brain of one human (“the sender”) and TMS is used to encode that information into the brain of another human (“the receiver”). Namely, the image that the sender is viewing is determined by monitoring oxygenated blood flow patterns in the brain and transmitted directly to the brain of the receiver. The receiver “sees” the image viewed by the sender through TMS-induced phosphenes which are elicited by stimulating with parameters determined during the mapping stage. This brain-to-brain interface allows for the transmission of complex visual information directly from one human brain to another and does so through noninvasive methods.

Natacha is a senior international student in the Department of Bioengineering at UW. Inspired by how immunity can be engineered using novel biomaterial platforms, she joined Dr. Kim Woodrow’s laboratory in her second year. With the support of the Levinson Emerging Scholar Program, she has been developing nanoparticles that program dendritic cells for use in vaccination to help prevent sexually transmitted infections such as HIV. Natacha is also an Undergraduate Research Leader for the Undergraduate Research Program and the Academic Chair for the UW’s chapter of the Biomedical Engineering Society (BMES). Through these leadership roles, which have provided her platforms to share her passions in research, she has promoted undergraduate research, particularly in the international student community. Following graduation, Natacha is planning to pursue a Ph.D. to prepare for a career in biomedical research. Natacha is grateful for her research mentors, Dr. Kim Woodrow and Dr. Jaehyung Park, who have enthusiastically provided continued guidance in her research and invested in her educational and personal development. She would also like to thank Dr. and Mrs. Arthur D. Levinson for their generous support that has empowered her to focus on her research with great zeal and drive.

Mentors: Kim Woodrow, Bioengineering

Project Title: Multifunctional Nanoparticles for Dendritic Cell-Based Intravaginal Vaccine against Sexually Transmitted Infections

Abstract: A majority of sexually active individuals will acquire sexually transmitted infections (STIs) sometime in their lives. The high prevalence of STIs stresses the need of developing effective STI vaccines. Compartmentalization of vaginal mucosal immunity, as well as the immunosuppressive immunity exhibited by the Langerhans cells in vaginal mucosal tissue, pose challenges in developing efficacious STI vaccines. To address both of these challenges, I propose the development of multifunctional nanoparticles for programming ex vivo dendritic cells (DCs) which can subsequently be delivered intravaginally to stimulate Langerhans cells (LCs) in the vaginal epithelial tissue. Development of the nanoparticles will involve optimizing co-delivery of antigen-encoded DNA and adjuvant to DCs, followed by testing for DC maturation and proinflammatory cytokines (IFN-Υ, IL-12 and IL-1β) release. Functional activation of T cell proliferation by nanoparticle-treated dendritic cells will also be tested to investigate the antigen presentation capacity of the programmed DCs. The process of developing the DC-programming nanoparticles will improve our understanding in controlling DC phenotypes and associated vaginal mucosal immunity against STIs. In the future, this project also has important direct applications in the development of the DC-based intravaginal vaccine, which can enhance vaginal mucosal immunity and potentially be translated to efficacious vaccines against various types of STIs.

Soley Olafsson is a senior in Bioengineering with Departmental Honors. Soley’s research experience began in Dr. Regnier’s Heart and Muscle Mechanics Lab when she was motivated by their strides in investigating heart failure therapies. Her research is focused around a novel therapy to improve cardiac function in injured myocardium. Cardiovascular disease affects so many people worldwide and Soley hopes to be part of the effort to diminish this problem.
In the future Soley hopes to continue to be on the forefront of helping those with cardiovascular disease by pursuing her MD and possibly becoming a cardiologist. Outside of the lab, Soley participates in bioengineering outreach to teach teens about the possibilities of pursuing a future in the sciences and serves on the executive council of her sorority, Gamma Phi Beta. Soley would like to recognize the remarkable support and help of her mentors Dr. Mike Regnier, Dr. Farid Moussavi-Harami, and Dr. Maria Razumova. Furthermore, she is very grateful to the Levinson Emerging Scholars Program for the confidence in her research to allow her to dedicate maximal time and effort.

Mentors: Michael Regnier, Bioengineering

Project Title: Protocol Development for Deoxyadenosine Triphosphate Quantification in Cardiac Tissue

Abstract: Heart failure is one of the leading causes of morbidity and mortality worldwide. Heart failure (HF) is the inability of the heart to keep up with its workload and at least half of HF patients suffer from decreased ventricular contractility or systolic dysfunction. Improving cardiomyocyte contraction is a potential therapy for diminished heart systolic function. There is no current effective therapy that directly improves cardiomyocyte contraction. Previous studies from our group (the Regnier lab) have shown that heart muscle exhibits a significant increase in contractility and force when naturally occurring 2-deoxyadenosine triphosphate (dATP) is used in place of adenosine triphosphate (ATP) as the substrate for contraction. Intracellular dATP levels can be elevated by the overexpression of the enzyme ribonucleotide reductase (RNR) that constitutes the rate-limiting step in de novo deoxynucleotide synthesis. In order to assess the efficacy of this alternative myosin binding substrate as a potential therapy, it is necessary to develop a reliable and accurate method to quantify the dATP levels in cardiac tissue and/or cultured cells. High Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS) has the greatest potential to detect both ATP and dATP analytes. My project is to develop a protocol for tissue sample preparation to run in the HPLC-MS/MS for quantitative assessment of nucleotides. I am using an iterative process to maximize reproducibility and reliability of nucleotide extraction. A standard curve will be produced to allow for absolute quantification of the nucleotides. Finally, I will implement these methods to study the cardiac levels of nucleotides in a transgenic mouse that overexpresses the enzyme attributed for de novo dATP synthesis on dATP levels. Correlation of dATP levels and cardiac function will provide validation of the influence of elevated dATP to improve cardiac muscle contraction for use in studies of animal models of heart failure.

Jazmine Perez is a senior majoring in Physiology and Gender, Women, Sexuality studies. Junior year, she joined the de la Iglesia lab, a circadian rhythms lab, to continue the work her mentor, Jennifer Gile, had begun with Dr. Benjamin Smarr: researching the modulation by the circadian system on cortical signals associated with wheel running. The goal of the research is to understand cortical signaling associated with motor behavior. Currently, the neuronal-prosthetics being developed and tried on non-human primates (NHPs) and humans don’t take into account any modulation on these signals from the central nervous system. The research will contribute to the development of brain-computer interface (BCI) devices like these that can be utilized over a 24h day. Jazmine would like to thank Jennifer Gile, Dr. Horacio de la Iglesia, Dr. Benjamin Smarr, Oliver Johnson, Dr. Howard Chizeck and Dr. Miriam Ben-Hamo for all of their support. It is the possibility of expanding her research based on new data and working independently that has encouraged her to pursue a Ph.D. instead of an M.D and continue in scientific research.

Mentors: Horacio de la Iglesia, Biology

Project Title: Circadian Modulation of Neuromotor Control

Abstract: Motor behavior is the result of neural programs emerging from the Primary Motor Cortex (PMC). In order for the PMC to generate behavioral outputs it integrates exogenous and endogenous sources of variance. Electrical activity from the PMC has been effectively used to operate minimally invasive brain-machine interfaces (BMIs) that can operate prosthetic limbs to achieve basic motor outcomes such as operating a joystick. Further development of neuroprosthetic technology will rely on a deep understanding of sources of variance to the PMC and how the PMC compensates for this. The circadian system regulates physiology and behavior within the 24-hour time frame and it represents a predictable source of endogenous variance for the generation of motor behavior. The specific pathways by which the circadian clock(s) may modulate PMC motor programs is not understood, but results from our lab have shown that the circadian system modulates the PMC electrical activity associated with wheel running in mice. We implanted electrocorticographic (ECoG) electrodes onto the PMC of mice and recorded electrical activity while they ran on a wheel at different circadian times. This has shown that the PMC electrical signals associated with wheel-running are modulated in a predictable manner by the circadian system. I propose to replicate these experiments in mice with a malfunctioning circadian clock. I hypothesize that the canonical molecular circadian clock is essential for this modulation. To test this hypothesis, I will use ECoG electrodes to record PMC electrical activity of Bmal1-/- mice, which have no copies of the clock gene BMAL1, and their wildtype (Bmal1+/+) littermates. This will determine whether the circadian modulation of the PMC depends on an intact molecular circadian clock. Understanding the regulatory effects of the circadian system on PMC brain wave activity is crucial for the design of BMIs and their effective operation throughout the 24-hour day

Alexandra is currently a senior in the Department of Mechanical Engineering. During her sophomore year, she joined the Ability & Innovation Lab, under Dr. Katherine Steele, which focuses on utilizing principles of engineering to improve human movement. There, Alexandra has been working on designing orthotic solutions to empower human mobility through human-centered design. Her current project involves designing affordable and customizable orthoses for individuals with limited hand function by leveraging existing 3D-printing technologies. With her research on 3D-printed orthoses, she has explored the possible applications of additive manufacturing techniques to the fabrication of affordable orthoses. In addition, she has worked on determining the rehabilitative potential of such devices to restore hand function among individuals with spinal cord injury. After the designs are finalized, they will be made open-source to accelerate improvements in orthotic device through collaborative innovation among the general public. Upon graduating from the University of Washington, Alexandra intends to pursue graduate research in mechanical engineering, focusing on developing innovative solutions in prosthetics aimed to improve the user acceptance rate of such devices. After graduate school, she hopes to continue working on developing prosthetic solutions at the Veterans Association hospitals, improving the standard of care for American veterans. Alexandra would like to thank her research team at the Ability & Innovation lab as well as Dr. and Mrs. Levinson for allowing her to focus more on the research project she is passionate about.

Mentors: Katherine Steele, Mechanical Engineering

Project Title: 3D-Printed Open-Source Hand Orthoses for Individuals with Spinal Cord Injury

Abstract: Affordable 3D-printing technology has added a new facet to manufacturing techniques that may help improve the fabrication and accessibility of orthoses. Wrist-driven orthoses (WDOs) are prescribed for individuals with spinal cord injury (SCI) at the 5th or 6th cervical levels who exhibit strong muscle activity in the wrist extensor muscles and little to no mobility in the fingers. By utilizing wrist flexion and extension, this device assists in opening and closing of the hand, enhancing performance of activities of daily living. This study focuses on reducing the complexity and fabrication time of hand orthoses and increasing their availability by leveraging 3D-printing technology and open-source designs. Future orthotists were asked to assemble and rate our 3D-printed WDO. During this testing phase, the fabrication time was 7 times faster than traditional methods and the device received average scores of 6.3, 6.6, 6.3, and 9.7 on its function, aesthetics, comfort, and fabrication speed, respectively (1=slow/poor, 10=fast/great). We used the participants’ feedback to improve the design and fabrication method. My primary research goal for the next year is to evaluate the device from the end users’ perspective by fitting participants with the 3D-printed WDO, testing its effectiveness with hand function and strength tests, and using their feedback to further refine the design. Additionally, we aim to expand the design to be used by individuals who cannot move their wrist or fingers. We have created an initial prototype of a design, which uses elbow motion to flex and extend the fingers and will further refine this design through testing with orthotists and individuals with SCI in the coming year. With this project, we aim to make these designs open-source to reduce the costs, increase access, and accelerate future development of orthoses to improve quality of life for individuals with SCI and other neurologic disorders.

Amanda Qu is a junior majoring in Biochemistry. Her interest in structural biology arises from a casual obsession with protein ribbon diagrams in high school. However, she did not realize this was what she wanted to research until she joined the Catterall lab in the summer after her freshman year at the UW. Her research centers around structural studies of CavAb, a bacterial voltage-gated calcium channel, using X-ray crystallography. Her current project involves designing a mutation in one of the crystal packing sites of CavAb to create a zinc-binding site that will strengthen the protein crystals. Ideally, this will increase the resolution of structures of CavAb, allowing her and her lab some insight into how some commonly used calcium channel blockers interact with voltage-gated calcium channels. Now, beyond pretty ribbon diagrams, Amanda is fascinated by how structural studies can elucidate the mechanism of biological functions at a molecular level. After graduation, she intends to pursue a Ph.D. in Structural Biology, Biophysics, or a related field and hopes to conduct research as a career after graduate school. Alongside that, she would like to advocate for diversity and equal representation in science. Amanda would like to thank her mentors Professor Catterall, Professor Zheng and Teresa Swanson for support in her research project. She is also grateful for the support that the Levinson Emerging Scholars Program is providing her in her undergraduate research experience.

Mentors: William Catterall, Pharmacology

Project Title: Design of a Zinc-Binding Site to Improve Structure Determination of a Voltage-Gated Calcium Channel

Abstract: Voltage-gated calcium channels are vital to electrical signaling in the human body, especially within the heart. The 3-D molecular structure of these channels is valuable information, since it forms the physical basis for their function of selectively allowing calcium ions through the cell membrane. Protein structures are most frequently found using X-ray crystallography, a technique in which a protein is grown into crystals and then diffracted with X-rays. Members of the Catterall lab use X-ray crystallography to study the structure of CavAb, the voltage-gated calcium channel of the bacterium Arcobacter butzleri. However, crystals of CavAb currently give structures with low resolution, because the crystals are weak and easily damaged by high-energy X-rays. This makes it difficult to see specific details in the protein’s structure, and thus limits the usefulness of these structures. My project involves introducing a zinc-binding site into CavAb, thus increasing the strength of the protein-protein interactions that cause it to crystallize. I anticipate that crystals of this altered form of CavAb, when grown in the presence of zinc, will incorporate zinc into the introduced binding site and result in a stronger crystal. If the structure of these crystals show evidence of an ordered zinc-binding site at the location where it was introduced and diffract to a higher resolution than previously obtained with this protein, this prediction will prove correct. Further applications of this project could include taking advantage of the anticipated increased resolution from this zinc-binding site for further studies on CavAb; for instance, greater resolution will allow our lab to fully determine the mechanism of action by which calcium channel blocker drugs, which are often used for cardiac disorders, bind to a voltage-gated calcium channel. Furthermore, similar introduced metal-binding sites could be applied to the crystallization of other proteins that do not otherwise form diffraction-quality crystals.

Oliver is a senior double majoring in bioengineering and neurobiology and is a member of the undergraduate computational neuroscience program. Over the last year, he has worked in the lab of Dr. Chet Moritz investigating electrophysiological interventions for artificial sensory feedback and for improving recovery from spinal cord injury. His current work focuses on developing a novel spinal cord injury rehabilitation technique. This last summer, Oliver attended a research experience for undergraduates hosted by the NSF Center for Sensorimotor Neural Engineering at the UW campus. During the 10-week program he completed the foundations of his current work by adapting a high-precision haptic interface device for use in animal training experiments. This system provides an extremely accurate representation of an animal’s motor activity. Oliver is now working on using this system for discriminating between different movements, which will allow the augmentation of rehabilitation exercises by using electrical stimulation to reinforce attempted movements and activate spinal neural plasticity. Outside of college classes, Oliver enjoys cycling, rock climbing, and engaging with new subjects through online courses and hackathons. After completing his undergraduate education in only three years, Oliver plans to pursue a Ph.D. in bioengineering, focusing on neural engineering and brain-computer interfaces and working to develop technologies to assist people with sensory and motor neural function deficits.

Mentors: Chet Moritz, Physiology, Biophysics

Project Title: Haptic Interface Device to Quantify Spinal Cord Injury Recovery Effects of Activity-Driven Intraspinal Microstimulation

Abstract: Spinal cord injury (SCI) can severely impair quality of life. While there are a variety of accommodations for individuals with SCI, there are no treatments which restore pre-injury levels of function to these patients. Developing such treatments requires exploration via animal models. Assessments of trained motor behavior in animal models of SCI recovery typically fail to capture information about fine gradations in the course of recovery, which interferes with the development of new restorative treatments. To better characterize these gradations during the study of a novel method for SCI rehabilitation, I propose the use of a high-precision haptic interface device to monitor an animal’s motor activity during a free exploration task and use this information to deliver targeted intraspinal microstimulation (ISMS) to enhance attempted movements. ISMS uses electrical impulses delivered through microwires implanted in the spinal cord to help activate neural tissue and promote motor responses. This will produce greater functional recovery by taking advantage of neuroplasticity to strengthen motor responses along undamaged pathways after SCI. Stimulation will be delivered to motor neurons which innervate the muscles driving movements detected by the haptic device, such as stimulating triceps motor pools when an animal attempts elbow extension. I hypothesize that movement-dependent ISMS targeted at the muscles responsible for that movement will improve recovery of function from SCI as measured by range of motion, muscle strength, and spasticity. Ultimately, the success of this project will contribute to helping individuals with disabilities due to spinal cord injury to regain function and independence.

Christine is a senior in the Department of Bioengineering at the University of Washington. Her interest in translational research was sparked when she was introduced to stimuli-responsive polymers for anticancer drug treatment in her bioengineering class. She was soon captivated by the vast potentials biomaterials have to offer in drug delivery and the possibilities of controlling physiological systems at a nanomolecular scale. Upon joining Dr. Patrick Stayton and Dr. Anthony Convertine’s lab, she began working on a nanoparticle drug delivery project for intracellular antimicrobial therapy. She synthesized a series of nontoxic and biodegradable nanoparticles with controllable hydrodynamic diameters. With the support of the Levinson Emerging Scholars Program, Christine is currently in the process of conjugating antibiotics to these nanoparticles for further therapeutic efficacy. With her passion for biomedical engineering, Christine is actively involved not only in her research but also in the UW Bioengineering Department. She is currently the Vice President of the UW Biomedical Engineering Society, undergraduate representative for the BIOE Student Advisory Board, and a pre-Bioengineering First-Year Interest Group (FIG) instructor. After completing her undergraduate studies, Christine plans to pursue a Ph.D. in biomedical engineering, specifically in the field of targeted drug delivery and tissue engineering. With her passion for translational research and advances in medical care, Christine hopes to contribute to the development of next-generation therapeutics in the near future. Christine would like to thank her mentors, Dr. Stayton and Dr. Convertine along with graduate students in lab, for their invaluable guidance and support throughout her journey as an undergraduate researcher, as well as Dr. and Mrs. Arthur D. Levinson for their generous support in her research.

Mentors: Patrick Stayton, Bioengineering

Project Title: Polymeric Nanoparticles for Intracellular Antibiotic Therapy against Tularemia and Melioidosis

Abstract: Francisella tularensis and Burkholderia pseudomallei, the agents of tularemia and melioidosis, respectively, have been identified by the Centers for Disease Control and Prevention (CDC) as bioterrorism agents that could lead to mass casualties and severe threat to public health. These pathogens are highly infectious and aerosolizable intracellular alveolar pathogens that can cause fatal respiratory tract infections. The intracellular compartmentalization of these pathogenic organisms within alveolar macrophages is a significant barrier to bacterial clearance and contributes to their associated morbidity and mortality. Currently, there is no effective treatment to eradicate melioidosis and tularemia other than prolonged antibiotic therapy and even with several months of intensive antibiotic treatment, complete clearance of these pathogens is not guaranteed. Therefore, there is an urgent clinical need to develop new therapeutic drug nanocarriers that can deliver antibiotics intracellularly to alveolar macrophages to increase treatment efficacy of tularemia and melioidosis. The goal of this project is to design biodegradable and nontoxic polymeric nanoparticles with various drug release rates and drug loading densities to overcome pathogens’ drug resistance mechanisms. The nanoparticle scaffolds will be synthesized using Polysorbate 80 via Thiol-ene and Thiol-Michael “click” reactions to maintain biocompatibility while incorporating functional groups that are amenable to chemical modification for enhanced drug loading. Once the nanoparticle scaffolds are characterized, they will be conjugated to antibiotics such as doxycycline via hydrolytically degradable ester bonds. Drug release profiles will be characterized in serum containing media via reverse phase HPLC to evaluate their efficacies. Once doxycycline is conjugated to the nanoparticle scaffolds, in vitro studies will be conducted to evaluate the polymeric nanoparticles’ therapeutic efficacy and toxicity in co-culture macrophage models of bacterial infection. Development of these polymeric nanoparticles will lead to rapid clearance of tularemia and melioidosis with shorter antibiotic administration while reducing the chances of relapse and antimicrobial resistance.