2011-12 Levinson Scholar
Spurred by a lifelong passion for prehistoric life, Jeff Benca’s research uses modern and fossil representatives of ancient plant lineages to study ecosystem dynamics and environmental changes in deep time. Joining the lab of paleobotanist Dr. Caroline Stromberg in the UW Department of Biology his sophomore year, Jeff began implementing extant plants from teaching and research collections he built at the UW Botany Greenhouse to study evolutionary trends in early vascular plants. With Dr. Stromberg, he studied morphological variation in modern clubmosses and later the extinct Devonian lycopsid genus Leclercqia across six continents and 12 million years, resulting in the description of a new species from Northern Washington State.
Now, Jeff is exploring whether leaf morphology in living lycopsids and ferns, plant groups that once dominated many of earth’s ecosystems ~360 million years ago, is influenced by climate. Conducting growth chamber experiments growing lycopsids and ferns under two temperature regimes he hopes to find out whether temperature can induce changes in leaf shape. If temperature does influence leaf physiognomy of these plants, it may be possible to calibrate fossil leaves of their ancestors as new tools for assessing paleotemperatures during the Late Paleozoic. Developing more accurate temperature baselines during this time period is particularly important as it could yield entirely new analogs to modern climate change. In the coming years, Jeff plans to pursue a PhD using living and fossil plants to better understand environmental changes associated with mass extinctions and climatic changes in the distant past while making paleobiology more accessable and hands-on for students and the general public through teaching and continued outreach.
Mentor: Caroline Stromberg, Biology
Project Title: Climatic Influences on lycopsid and fern leaf physiognomy
Abstract: Understanding modern climate change hinges upon our ability to assess past climates. While relatively few analogs to modern climate change are represented in recent geological history, the Paleozoic era may offer more. Investigating Paleozoic climates could allow for study of long-term impacts of dramatic environmental transitions on terrestrial ecosystems. But exploring climate shifts in the distant past will require the expansion of existing techniques. Several methods use fossil leaf morphology to infer past climatic conditions. One such approach called Leaf Margin Analysis (LMA) uses leaf margin toothiness to infer past mean annual temperature. This approach has proven successful in using modern floras to estimate regional climates but can only assess past climates as far back as 120 million years ago (Ma) since it currently only utilizes leaves of flowering plants. However, other more ancient groups of vascular plants have evolved leaves with toothed margins as well. With toothed leaves and a fossil record exceeding 350 Ma, lycopsids (clubmosses) and ferns have potential to extend LMA back to the Late Paleozoic. To determine whether climate (in particular, temperature) influences leaf morphology in living representatives of these lineages, we are growing two species of lycopsid and two species of fern under two temperature regimes; 15°C and 25°C. If tooth number or size increases under cooler temperatures, fossil relatives of these ancient vascular plant lineages could potentially be implemented for study on climate changes long-preceding the age of flowering plants.
Ben Dulken is currently a senior in the Bioengineering department. He got his first exposure to biomedical research as a lab assistant in the Kaeberlein Lab (UW Patholgy) during his freshman year. He was drawn to research by the opportunity to apply what he had been learning in his classes to achieve clinically relevant findings which could improve the quality of life for suffering individuals. He spent about a year in the Kaeberlein Lab investigating the genetic mechanisms of aging in yeast. Subsequently, Ben moved to the lab of Prof. Suzie Pun in the Department of Bioengineering to investigate novel drug delivery materials. While in the Pun Lab, Ben has been involved with several projects including the development of a micelle delivery system for solid tumor imaging agents and chemotherapeutics, and his current project, the investigation of a novel drug loaded hydrogel to provide controlled delivery of an ototherapeutic agent to the inner ear over an extended period of time. Throughout his undergraduate career he has participated in several research-oriented programs including the Amgen Scholars Program and the DAAD Research Internships in Science and Engineering. He plans to continue to pursue his passion for biomedical research by pursuing an MD/PhD. When he is not in the lab, Ben enjoys cycling, hiking, and playing the piano.
Mentor: Suzie Pun, Bioengineering
Project Title: Novel hydrogel for the delivery of cochlear therapeutics using complexation of ß-cyclodextrin conjugated PEO-PHB-PEO triblock copolymers and adamantane conjugated multi-arm PEGs.
Abstract: The loss of the hair cells of the cochlea of the inner ear can result in permanent hearing loss. Recently, the Rubel lab (UW Otolaryngology) has identified a molecule which can prevent hair cell death induced by the antibiotic neomycin, however, they have had difficulty delivering PROTO1 to the inner ear. This project involves the design, formulation, and characterization of a novel drug loaded hydrogel for delivery of PROTO1 to the inner ear. The drug loaded hydrogel will be applied at the round window membrane of the cochlea via surgical insertion. Over an extended period of approximately three to four weeks the drug contained in the hydrogel will be released and diffuse through the round window membrane into the fluid paths of the cochlea, where it is therapeutically active. The design will use modified PEO-PHB-PEO triblock polymer which will be cross linked by the interactions of adamantane and ß-cyclodextrin. The hydrogels will be composed of a mixture of ß-cyclodextrin conjugated triblock copolymers and adamantane conjugated multi-arm PEG. When these two polymers types are mixed, inclusion complexes between the adamantane and ß-cyclodextrin moieties will cross link the polymers and induce the formation of a supramolecular hydrogel. This work builds on previous work which has demonstrated the formation of hydrogels when the PEO-PHB-PEO triblock copolymer is cross linked with a-cyclodextrin This design is superior to its predecessor in that it could potentially allow for hydrogel formulation at lower polymer concentrations, and could potentially increase the stability of the hydrogel, sustaining drug release over a longer period of time. Hydrogel preparation parameters will be optimized by investigation of the thermosensitive, viscoelastic, and drug release properties of the hydrogel. The in vivo therapeutic efficacy of the drug loaded hydrogel will be measured in a rat or guinea pig model.
Both biology and issues of mental health have interested Molly since she was in high school. For the past two years, she has been able to work in both of these fields as she investigates a mutation in the DNA of a patient with schizophrenia. She has pursued this research under the mentorship of Dr. Mary-Claire King, in the departments of Medical Genetics and Genome Sciences, and Caitlin Rippey, a graduate student in the UW’s Medical Scientist Training MD/PhD Program. With the support of the Levinson Scholarship, Molly hopes to complete her analysis of this mutation and contribute to the understanding of the biological mechanisms of schizophrenia. This research experience, combined with her biology major and experience in activism for mental health awareness, has inspired her to pursue graduate school and a career in neurogenetics research.
Mentor: Mary-Claire King, Genome Sciences and Medicine
Project Title: Biological characterization of a genetic mutation implicated in schizophrenia
Abstract: Schizophrenia is a devastating neurodevelopmental disorder whose genetic influences continue to be elusive. Rare, gene-disrupting genomic deletions and duplications – called copy number variants (CNVs) – have been implicated in schizophrenia; however, much remains to be understood about which genes are causative, as well as the cellular mechanisms involved. Biological follow up on individual CNVs will give insight to the origin of schizophrenia. We focused on one that duplicates the 5′ ends of two genes that lie head-to-head on chromosome 11q22: DCUN1D5, a previously uncharacterized gene predicted to be involved in cullin neddylation of ubiquitin ligase complexes, and DYNC2H1, a dynein active in cilia. Both are expressed in brain and are plausible candidate genes for schizophrenia. Using RNAseq, we detected novel DCUN1D5 transcripts that we predict will result in truncated DCUN1D5 protein in the patient’s cells. In order to understand the function of DCUN1D5, we will determine which of seven possible cullin binding partners it interacts with using an in vitro neddylation assay. We will then test the conformational stability of truncated DCUN1D5 by Western blot in the patient’s cells and transfected cell lines. We will then be able to compare the function of the full length DCUN1D5 with the aberrant DCUN1D5 present in the patient. Investigation of these aberrant proteins may shed light on pathways that contribute to schizophrenia, potentially guiding the search for new candidate genes and the development of novel treatment strategies.
Teague Henry is interested in the methodology currently used to study psychology phenomena, specifically methods used to study social networks from a psychology perspective. After joining Kevin King’s lab during his sophomore year, he has been involved in a variety of projects investigating the role of impulsivity on substance use. The project funded by the Levinson will investigate the role of peers on individuals substance use. Currently, Teague is a senior working towards a major in psychology, with minors in mathematics and philosophy. He hopes to pursue a graduate degree in quantitative psychology, and continue to research and develop analytical techniques to investigate more complex problems in psychology.
Mentor: Kevin King, Psychology
Project Title: Context and Peer Influence on Adolescent Substance Use
Abstract: Adolescent substance use is a significant public health issue in America. Research has established that one of the best predictors of adolescent substance use is peer substance use. One of the processes that lead to this similarity in behavior is peer influence. Previous research has established that several factors, such as self-regulation, moderate an individual’s susceptibility to peer influence. However, little research has been done as to the effect of peer network characteristics and contextual characteristics on susceptibility to peer influence. The proposed study will investigate the effects of self-regulation alongside with peer network characteristics and contextual variables on susceptibility to peer influence. This study will use the Add Health dataset, a nationally representative longitudinal survey of adolescents. The data will be analyzed in a multi-level framework to simultaneously determine the effect of individual characteristics, peer network characteristics and contextual characteristics. Findings of this analysis will provide insight about the role of both environmental context and social context in determining an individual’s susceptibility to peer influence in regard to substance use.
Since his first year as an undergraduate, Marvin Nayan has been engaged in neurobiology research at the Parrish Laboratory, where he investigates the genetic and molecular mechanisms responsible in regulating dendrite branching. Due to the importance of dendrite patterning to nervous system function, dendrite abnormalities have been linked to many neurological diseases. Marvin’s current research focuses on identifying and characterizing mutations that are defective in the development and maintenance of sensory neurons in fruit fly. Marvin hopes his research will lead to improvements in the diagnosis and treatment of many mental disorders. Thus far, Marvin’s research has guided him to be recognized as a Mary Gates Research Scholar, EOP Scholar, and EIP Presidential Scholar. With the generous support of the Levinson Emerging Scholars Program, Marvin intends to continue neurobiology research in graduate school and plans to pursue a career in academia.
Mentor: Jay Parrish, Biology
Project Title: Characterizing the Metabolic State of Cancer and Embryonic Stem Cells
Abstract: Dendrites are branched projections of a neuron that chiefly function as information receivers, conducting stimuli from adjacent neurons or the external environment and relaying those synapses throughout the body of an organism. This elaborate, yet efficient, transfer of information from neuron to neuron is the hallmark of the nervous system. Therefore, any abnormality that alters how a neuron receives stimuli, such as the spatial arrangement of its dendritic arbor, can lead to defects in neuronal function. Given the importance of dendrite morphology to neuronal function, it is essential for neurons to maintain optimal coverage of their receptive field as the organism grows in size. However, the mechanisms underlying this phenomenon are poorly understood. We propose a genetic screen to identify genes that regulate maintenance of dendrite coverage. Our aim is to perform functional gene analysis and identify extrinsic regulators of dendrite maintenance. To this end, we will use a transgenic line of fruit flies bearing membrane-bound fluorescent proteins to visualize dendrites of dendritic arborization neurons in the peripheral nervous system. Following chemical mutagenesis, we will use confocal microscopy to screen for mutations that are defective in dendrite maintenance. Subsequently, I will characterize the site of action of mutations of interest using mosaic analysis and finally will positively identify the gene affected by a given mutation by performing a genetic rescue via P-element-mediated transformation. Results from this project will lead to greater understanding of neuronal development, including potential implications to many neurological diseases.
Having cultivated an interest in computer technology since childhood, Bennett Ng discovered a passion for bioengineering during his junior year of high school. As an intern at Seattle BioMed, he gained first-hand experience with infectious disease research, and found a humanitarian purpose to guide his interest in computing. These experiences led him to become a student in the UW Department of Bioengineering, where he quickly joined Herbert Sauro’s synthetic biology lab to continue pursuing student research. As a sophomore, Bennett conducted computational research to elucidate optimal design targets in biochemical networks. Now as a senior, he is synergizing his interdisciplinary interests to develop a low-cost, open-source chemostat device in the Sauro lab. The device could enable and accelerate evolutionary stability experiments which are essential to the advancement of synthetic biology. Bennett is a dual-major in Bioengineering and Computer Engineering. Outside of the lab, he is actively involved as an officer for the Biomedical Engineering Society and Bioengineers Without Borders. He plans to pursue graduate study and a career in biotechnology industry.
Mentor: Herbert Sauro, Bioengineering
Project Title: Design of a Modular, Integrated Growth and Measurement System for the Extended Characterization of Biological Parts
Abstract: A key issue in synthetic biology is the evolutionary robustness of synthetic circuits. Creation of robust circuits requires the development of design criteria to extend evolutionary timescales, and insight into the relative evolutionary fitness of different circuit designs. Experimentally, this research requires the use of multiple cell culture runs that are time-consuming and laborious. To accelerate this work, development of a high-throughput, automated, and parallel mini-chemostat and turbidostat device is proposed.
While the development of nutrient-replenishing chemostat devices dates back to 1950, and the usage of such devices is well-documented, even modern chemostats are not well-suited to evolutionary experiments. Current designs face significant issues of equipment fouling, specialized complexity, and prohibitive cost. Presently there is a lack of cost-effective options for highly parallel milliliter-scale chemostat devices which can be applied to problems in synthetic biology.
The proposed device will be small and modular, utilizing multiple standard petri dishes for parallel culture experiments. The design will feature integrated media refreshment and temperature control mechanisms. Visible and fluorescent direct-view, real-time imaging systems will be included. The device will be constructed of readily-available parts to maintain low cost. Parts will be modular such that used petri dishes can be easily removed, disposed of, and replaced. The design will be scalable such that numerous devices can be stacked or tiled for parallel experiments. An open-source software package and electronic microcontroller system will be developed to allow for automated real-time measurement and customization of growth and measurement parameters.
Eric Secrist is a senior at UW who has always been intrigued by the nervous system, particularly the areas which are not fully understood. He began working in Dr. Chet Moritz’s spinal cord injury lab in the rehabilitation medicine department during his sophomore year in order to pursue this curiosity. With assistance from Dr. Moritz and Dr. Mike Kasten, Eric developed and is currently conducting a brain-computer-interface experiment which links dopamine releasing medial forebrain bundle stimulation with functional movements of an impaired limb. The hope is that this research will contribute to the development of novel therapies for people with partial spinal cord injuries to regain movement in their arms and hands. After graduating this spring with a degree in Physiology and a minor in Bioethics and Humanities, Eric hopes to go to medical school and continue following his interest in neuroscience by becoming a neurologist.
Mentor: Chet Moritz, Rehabilitation Medicine and Physiology
Project Title: Dopamine Mediated Plasticity and Its Role in Recovery from Cervical Spinal Cord Injury
Abstract: Thanks to advances in safety equipment and emergency care, most spinal cord injuries that occur in people today are incomplete, leaving a portion of the spinal cord neural tissue intact. Further, recent research has shown that there is plasticity and axonal sprouting following injury, expanding the possibilities for rehabilitation from what was once considered a permanent and unrecoverable injury. Our goal is to enhance this process and work towards functional recovery. Dopamine, a powerful neurotransmitter involved in processes such as learning, memory and motivation, plays an integral role in brain plasticity. We are currently testing whether pairing dopamine release with functional movements can increase plasticity of the remaining active pathways and lead to increased functional recovery following an injury. We will test this by comparing the recovery of two groups of rats following partial cervical spinal cord contusion injuries in only one forelimb. Both groups of animals will receive dopamine-releasing electrical brain stimulation. For one group this stimulation will be synchronized with movements of the impaired limb. These rats will activate the stimulation by using their impaired forelimb to push a lever. The other group will receive stimulation at a time separate from desired forelimb movements, but will still have to push the lever in order to receive it. In both groups this stimulation will activate the medial forebrain bundle, a pathway in the brain strongly associated with dopaminergic pathways. The two groups will be compared on their ability to perform specific motor tasks with the injured forelimb. We hope to someday apply the knowledge we gain from this experiment to develop novel ways to promote nervous system recovery from injury by using dopaminergic pathways to reinforce neural plasticity. This may lead to therapies which allow people with incomplete spinal cord injuries to improve their fine motor skills.
Alex Taipale came to the University of Washington from Colorado to study Biochemistry. She pursued her interest in research in Dr. Sarikaya’s Materials Science and Engineering lab and Dr. Yager’s Bioengineering lab. She finally found her passion for research when she began Human Immunodeficiency Virus Type 1 (HIV-1) research in Dr. Mullin’s Microbiology lab. During her time in the lab, she has worked on several different projects related to HIV-1 vaccine development. Her involvement in HIV research aroused her interest in HIV studies being performed with samples from female patients. Despite the fact that HIV-1 progresses differently in women than in men, there are far fewer HIV-1 studies conducted with female samples. Alex will spend her senior year studying HIV-1 evolutionary trends in female samples in order to make a comparison to the data generated in pre-existing male studies. After graduation, she hopes to continue her study of viral disease by pursuing a PhD in Microbiology or Biochemistry. Ultimately, Alex hopes to improve disease treatment and prevention through a career as a research scientist.
Mentor: James Mullins, Microbiology
Project Title: Sex Differences in Viral Evolutionary Trends Associated with the Progression of Human Immunodeficiency Virus Type 1 Infection
Abstract: The effect of viral evolution on the duration of latent Human Immunodeficiency Virus Type 1 (HIV-1) infection has been studied extensively in men. The asymptomatic latency period, after HIV-1 infection and before the onset of Acquired Immune Deficiency Syndrome (AIDS), is characterized by high viral variability. In many cases, a viral phenotype that utilizes CXCR4 and/or CCR5 receptors on target host cells to advance HIV-1 progression also emerges during this period. Despite known sex-dependent variation in the progression of HIV-1, the effect of viral evolution and CXCR4/CCR5 utilizing virus (X4 virus) prevalence on HIV-1 latency has not yet been studied in women. I will investigate trends in viral evolution in 9 women from seroconversion to the development of AIDS. I will then compare my results to previously studied male viral evolutionary trends. Over the course of three quarters, a total of 72 blood plasma samples, an average of 8 samples from each woman collected progressively during the course of infection, will be used to generate 25-30 HIV-1 sequences per time point. These sequences will then be evaluated through 1) viral divergence from a founder strain 2) viral population diversity and 3) emergence and prevalence of X4 viruses. I will then analyze the effect of viral evolutionary trends and X4 virus prevalence on the duration of HIV-1 infection before the onset of AIDS. Ultimately, a comparison between the sexes will be made. Furthering the scientific communities’ knowledge of sex-related HIV-1 infection variation could lead to more effective sex-specific treatment and vaccine development. The important biological question of whether sex can influence HIV-1’s evolutionary path will be addressed.