May 18, 2018 Mary Gates Hall

Are All Created Equal? Linking Diet to SESSION 1A Morphology in Phytophagous Jonathan Michael Huie, Junior, Aquatic & Fishery Sciences Mary Gates Scholar, UW Honors Program BUSINESS TOPICS RELATED TO Mentor: Adam Summers, Biology EARNINGS,FINANCE, AND Mentor: Matthew Kolmann, Friday Harbor Labs MARKETING Herbivorous fishes feed on stems, leaves, flowers, seeds, Session Moderator: Weili Ge, Accounting fruits, and nuts of diverse aquatic plants, as well as algae. MGH 074 In the Neotropics, many of these fishes have intricately tied 12:30 PM to 2:15 PM ecologies with their prey plant’s life history and facilitate seed * Note: Titles in order of presentation. dispersal; including the herbivorous cousins of piranhas, pa- cus. Most pacus experience fluctuation in their diet that re- Optimal Dynamic Pricing of Inventories with Stochastic flects the changes in seasonality and plant part availability. A Demand Functions for Online Fashion Retailers few of pacus, however, exhibit a specialized feeding Xiangjun (Aileen) Yang, Senior, Economics, Applied & strategy known as phytophagy; solely consuming the plant Computational Mathematical Sciences (Mathematical material of (riverweed). This trend of dietary Economics) specialization may be paralleled by a similar shift, away from UW Honors Program general herbivory, and towards a specialized phytophage mor- Mentor: Michelle Turnovsky, Economics phology. To investigate the link between diet and morphol- Mentor: Matthew Lorig, Applied Mathematics ogy within the greater scope of herbivory, we examined four coexisting species including: the seemingly specialized phy- This research deals with the specific dynamic pricing strategy tophage, Ossubtus xinguense; the generalized phytophages, of fashion products sold online. The pricing method works kranponhah and Tometes ancylorhynchus; and a fac- under the condition of a pre-determined quantity of inventory ultative phytophage, Myloplus rhomboidalis. We compared with stochastic demand functions on a limited time horizon, the gross morphology of these species with several other which is formulated as an optimization problem. To achieve serrasalmids using micro-computed tomography scanning to the maximized profit, it is essential to balance between the ex- measure functional jaw characteristics, as well as using geo- tra marginal revenue earned by setting a high selling price and metric morphometrics to compare body shapes. Jaw biome- the cost lost from unsold items. In order to find the solution, chanics indicate that O. xinguense produces the weakest jaw we first develop and estimate a pricing model that captures leverage potentially as a result of its sub-terminal mouth. the important characteristics of the fashion apparel market. However, we also concluded that the phytophagous species Afterwards, we use data from a leading Taiwanese fashion as a group, do not overtly differ from the more generalized retailer to examine the accuracy of our model. The final pur- herbivorous pacus in terms of jaw mechanics (but remain dis- pose of this research is to provide an insightful conclusion of tinct from the piscivorous piranhas). Body shape analyses the dynamic pricing policies that would generate the highest also show little divergence among phytophage and retailer revenues. body shapes, suggesting that many herbivores share a similar bauplan adapted for fast flowing waters. With the exception SESSION 1D of O. xinguense, phytophagous pacus appear to be equipped with a general herbivory feeding morphology sufficient for a specialized diet. This suggests that phytophagy is not a par- MARINE ECOLOGYAND FOOD WEBS ticularly challenging feeding strategy, but performance may Session Moderator: Bonnie Becker, Academic Affairs be augmented by additional morphological specialization. (Tacoma) MGH 228 12:30 PM to 2:15 PM * Note: Titles in order of presentation.

Undergraduate Research Program 1 www.uw.edu/undergradresearch Risk Assessment of Phytophthora alni in Washington SESSION 1G State Brandon E. Voelker, Junior, Environmental Science, UW Tacoma TOWARDS BETTER UNDERSTANDING Mentor: Matthew Kelley, Urban Studies OF HUMAN DISEASESTHROUGH Phytophthora alni is a species complex of pathogenic MOLECULAR BIOCHEMISTRY oomycetes (water molds) that can cause lethal disease in Session Moderator: Valerie Daggett, Bioengineering alder trees, Alnus spp. One variant, P. alni subsp. alni, is MGH 238 widespread across Europe, devastating stands of alder since 12:30 PM to 2:15 PM the 1990s. One less lethal member of the species complex, P. * Note: Titles in order of presentation. alni subsp. uniformis, has already been found in the wild in Alaska and Oregon, but not in Washington State. Recently, Design of an Alpha-Sheet Peptide for the Inhibition of it has been detected in potted alders in nurseries in Pierce Aggregation in AL Amyloidosis County. It is currently unknown whether any member of the Lauren Nicole Martini, Senior, Computer Engineering, P. alni species complex is in the wild in Washington, either Bioengineering naturally or through introduction from nursery plants. To be- Mary Gates Scholar gin efforts to detect Phytophthora alni in Washington State, Mentor: Valerie Daggett, Bioengineering a risk assessment map will be created using Geographic In- Mentor: Matthew Childers, Bioengineering formation System (GIS) techniques. The spatial analysis will involve examining the environmental factors that increase in- The misfolding and aggregation of free light-chains into amy- fection susceptibility, such as slope, soil grain size, and flood- loid fibrils is the hallmark of antibody light-chain (AL) amy- ing, and correlating with the distribution of alders. Important loidosis, a fatal disease associated with the accumulation of questions that could be revealed are whether high risk areas amyloid species in tissues throughout the body, including are upstream, where infection could spread, or downstream, the heart and kidneys. Current treatment options, including and whether high risk areas correlate with urban or agricul- chemotherapy and bone marrow transplant, do not address tural land use. The risk assessment will provide a starting the causes of aggregation on a molecular level. Molecular dy- point for choosing sampling sites, which is the next step in de- namics (MD) simulations were used to investigate misfolding tecting the existence of P. alni. Additionally, the final analysis pathways in the aggregation of two light chain monomers, Jto will inform forest management practices, as the highest risk and Wil. These simulations showed that under amyloidogenic areas could be inspected for symptomatic alders and mitiga- conditions, conversion from beta-sheet to alpha-sheet sec- tion measures could be enacted if any are found. The assess- ondary structure was observed in both Jto and Wil. Misfolded ment will also have implications for restoration sites, where conformations, obtained from the MD simulations, were used native trees such as alder are planted from nursery stock. to guide the design of alpha-sheet peptides, which have been used previously to inhibit amyloid formation in diverse sys- tems. The designed peptides were evaluated computationally SESSION 1M by docking them against misfolded conformations of Wil, and the best performing peptide was chosen for future experimen- IFEAND EATH IN THE CEAN tal work to explore its potential to limit aggregation. L D O Session Moderator: Virginia Armbrust, Oceanography MGH 284 SESSION 1L 12:30 PM to 2:15 PM * Note: Titles in order of presentation.

SOUNDTO MOUNTAINS:WATER, Use It or Lose It: Three Ways That Snailfishes LIFE, AND CLIMATE IN THE SALISH (Liparidae) Reduce Their Skeleton in the Deep Abigail (Abby) Von Hagel, Senior, Biology (Molecular, SEA Cellular & Developmental), Neurobiology Session Moderator: Peter Selkin, School of Interdisciplinary Mary Gates Scholar, UW Honors Program Arts & Sciences Mentor: Adam Summers, Biology MGH 271 Mentor: Stacy Farina, Friday Harbor Laboratories 12:30 PM to 2:15 PM Mentor: Mackenzie Gerringer, Friday Harbor Labs * Note: Titles in order of presentation. Mentor: Matthew Kolmann, Friday Harbor Labs

Skeletal reduction is a common feature among deep-sea

2 fishes that have diversified from shallow-water relatives, such (TLR7)—an innate immune receptor in airway epithelium as snailfishes. These skeletal reductions may be an adapta- that responds to single-stranded RNA viruses (like influenza) tion to environmental conditions of high pressures, low tem- and triggers an immune response to infection. TLR7 is also peratures, declining luminosity and limited food availability. expressed on airway sensory nerves, but its specific role is Snailfishes (family Liparidae) are found across a large bathy- unknown. Here, I tested the role of TLR7 on sensory nerves metric range (0 –>8,000 m), with intertidal ancestors giving and identified which sensory nerve populations express TLR7 rise to a large clade of deep-sea species. We used micro- using nerves isolated from dorsal root ganglia from female computed tomography (micro-CT) to estimate average bone Hartley guinea pigs (˜400 g). Ganglia were isolated, plated mineral density and examine jaw, pectoral girdle, and neuro- onto matrigel, and treated with a TLR7 agonist R837 (0.1- cranium morphology. Our results suggest at least three mech- 100 microM) for 16 hours. Neurite number per cell was not anisms of skeletal reduction: (1) reduction of bone size, (2) changed by stimulating TLR7, but neurite length, and the reduction of bone density, and (3) loss of skeletal elements. number of branch points were significantly increased. Sep- First, using phylogenetic generalized least squares (PGLS) arate experiments measured which types of sensory nerves analysis, we found that the change in cranial dimensions with expressed TLR7. Vagal and dorsal root ganglia were isolated depth was not uniform. While the size of the maxilla, den- and fixed in zinc formalin. Nerves were immunolabeled with tary, and pectoral girdle decreased with greater depth, length antibodies against TLR7 and either neurofilament-1 (NF-H) of the upper premaxilla and the neurocranium did not vary to identify A???? fiber sensory nerves or transient recep- with collection depth. Second, average density of the lower tor potential V1 (TRPV1) to identify C-fiber sensory nerves. jaw decreased with increasing depth. Lastly, the ventral suc- I found that airway sensory nerves originating in the vagal tion disc has been lost multiple times within the deep sea lin- and dorsal root ganglia expressed TLR7. However, TLR7 eage. While all three methods are seen in snailfishes, other was expressed predominantly on small TRPV1-expressing C- groups may use some or all of these mechanisms to different fiber neurons, but not on large NF-H-positive A???? neurons. extents. Some mechanisms of skeletal reduction may be more In conclusion, TLR7 is highly expressed by airway sensory advantageous than others. The extent to which a structure is C-fibers nerves, and its activation stimulates neurite growth. retained in deep-dwelling fishes may indicate its functional These findings suggest TLR7 may increase airway C-fibers importance. Variable skeletal reduction in the family Lipari- supplying the lungs which may enhance airway reactivity and dae provides insights into the physiological adaptations that be a mechanism for virus induced exacerbations of asthma. allow fishes to survive in deep-water environments. We con- clude that some skeletal elements are maintained at the ex- pense of others as fishes balance the functional demands of POSTER SESSION 2 life in the deep sea. Commons West, Easel 21 1:00 PM to 2:30 PM SESSION 1P Using Linguistic Knowledge to Resolve Ambiguity in Speech Perception When Hearing is Degraded Siuho Gong, Senior, Speech and Hearing Sci (Com MCNAIR SESSION -SCIENCEAND Disorders) TECHNOLOGYFROM CELLSTO Mentor: Matthew Winn, Speech & Hearing Sciences Mentor: Steven Gianakas OUTER SPACE Session Moderator: Laura Pina, Human Centered Design Sometimes speech sounds (phonemes) can be ambiguous, and Engineering and people have a tendency to interpret the ambiguous MGH 295 phoneme differently in different contexts so that they per- ceive a real word, as opposed to a non-word. This effect is 12:30 PM to 2:15 PM called ”lexical bias.” For example, when there is ambiguity * Note: Titles in order of presentation. between whether /m/ or /n/ is heard, /m/ is more likely to Stimulation of Neuronal Toll-like Receptor 7 on C-fibers be perceived if it is followed by ”uch,” because ”much” is Increases Nerve Growth in vitro a word, but ”nuch” is not (and vice versa if the context is Karol Wai, Senior, Biology, Portland State University ”udge”). We hypothesized that for people who have hearing McNair Scholar loss or use a cochlear implant, there will be additional ambi- Mentor: Matthew Drake guity in hearing speech, and that the lexical bias effect would Mentor: Becky Proskocil be stronger. We simulated degraded hearing using vocoded speech played to listeners with normal hearing. Participants Viral infection is associated with asthma exacerbations. Nor- heard speech continua that gradually morphed from /m/ to mally, viral presence is detected by Toll-like receptor 7 /n/ in the ”uch” and ”udge” contexts, and either had a clear

3 spectral quality or a degraded spectral quality. Results sug- levels. Validating these parameters in primary T cells will al- gest that the lexical bias is stronger when the speech signal low me to apply this T-bet overexpression vector in a mouse quality is less clear, which is consistent with the hypothesis model of T cell exhaustion. This tool has significant impli- because of the increased phonemic ambiguity in these condi- cations for improving immunotherapy strategies, such as TIL tions. By understanding how signal degradation impacts the and CAR-T therapies, where exhaustion of the therapeutic T perception of phonemes, audiological tests for speech recep- cells has led to reduced efficacy of the treatment. tion can be improved to separately acknowledge the effects of hearing from the adjustments that the listener makes to main- tain lexical biases in speech perception. POSTER SESSION 3 MGH 206, Easel 178 2:30 PM to 4:00 PM SESSION 2B Analysis of the Role of TGF-β/BMP Signaling Pathway ENHANCING IMMUNE RESPONSES in C. elegans Adult Reproductive Diapause Shruti Nagesh Karanth, Senior, Biochemistry TARGETING INFECTION,INJURYAND Mentor: Nikolay Burnaevskiy, Pathology CANCER Mentor: Matt Kaeberlein, Pathology Session Moderator: Kristin Anderson, Immunology Aging is a phenomenon that brings about the onset of many MGH 228 diseases and increases mortality. Understanding aging mech- 3:30 PM to 5:15 PM anisms can help us increase longevity and delay the onset * Note: Titles in order of presentation. of multiple chronic diseases. It has been previously ob- served that dietary restriction is a method that increases lifes- T-Bet Mediated Control of Effector T Cell Phenotypes pan and delays the loss of function caused by age-associated Leonard Daniel Chen, Senior, Bioengineering pathologies. We used the roundworm, Caenhorbabditis ele- Mary Gates Scholar gans, to dissect the mechanisms of dietary restriction-induced Mentor: Hao Yuan Kueh, Bioengineering longevity. Specifically, we focused on the phenomenon of Mentor: Matthew Wither, Bioengineering adult reproductive diapause (ARD). ARD is induced when pre-reproductive juvenile larvae are subjected to starvation. T cells of the immune system protect humans from most Upon reintroduction to food after prolonged starvation, ARD threats because they can recognize and eliminate foreign tar- worms undergo a morphological rejuvenation and resume a gets, as well as protect from reinfections. However, the per- normal lifespan. Mechanisms that control post-diapause re- sistence of an infection in the body leads to chronic stimu- covery are still quite unknown. We have found that the TGF- lation of T cells, causing them to lose their effector function β/BMP signaling pathway is required for post ARD rejuvena- and enter a state known as “exhaustion”. Exhausted T cells tion. The TGF-beta signaling pathway is a critical factor for are defined by increased expression of inhibitory receptors, growth processes including cell growth, differentiation, em- loss of immune cell regulation, and most importantly, loss of bryonic development, and much more. We aimed to charac- cytotoxicity and effector function. Studies have shown that terize the role of this signaling pathway in ARD maintenance the transcription factors, T-bet and Eomes, play crucial roles and post-ARD recovery. We hypothesized that TGF-β/BMP in regulating T cell differentiation, with T-bet being highly as- mutants accumulate excessive amounts of cellular damage sociated with effector T cell differentiation. T-bet expression during ARD and are unable to recover from ARD. To address is dampened in exhausted T cells, and therefore, I hypothesize this hypothesis, we analyzed markers of cellular aging among that controlled induction of T-bet expression can reverse the diapaused using fluorescent microscopy, in both wild exhausted phenotype in antigen-experienced T cells. I con- type and TGF-β/BMP mutants. Using transgenic fluorescent structed a T-bet overexpression vector containing T-bet cDNA reporter strains we examined pH, nucleolar morphology, mi- fused to a fluorescent protein and destabilizing domain. The tochondria, and cytoskeleton and nucleoskeleton integrity for destabilizing domain, or degron, facilitates degradation of the aging-associated phenotypes. These insights can help us un- constitutively expressed T-bet transgene in the absence of the derstand the role of the conserved TGF-β/BMP pathway in ligand, Shield-1, which when added at varying concentrations dietary restriction induced longevity. allows for a range of protein stability. This method of over- expression confers faster control kinetics compared to com- monly used transcriptional approaches, such as inducible pro- POSTER SESSION 3 moters. I have characterized the range of the T-bet transgene MGH 241, Easel 149 in Jurkat cells by titrating Shield-1 to provide a working range 2:30 PM to 4:00 PM of 5-60% overexpression of T-bet compared to endogenous

4 Role of Actin Cytoskeleton in Cellular Aging This effect is mediated by the inappropriate upregulation Miguel Arenas Mailig, Senior, Microbiology, Biology of a cohort of genes associated with the glucose starva- Mentor: Matt Kaeberlein, Pathology tion response despite replete glucose conditions. Deletion Mentor: Nikolay Burnaevskiy, Pathology of these genes—glucokinase (Glk1), phosphoglucomutase Aging is associated with a decline in functionality and cellu- (Pgm2), and glycogen synthase (Gsy1)—also results in in- lar organization. These changes are reflected in the morphol- creased lifespan. These genes are associated with the accu- ogy of cellular organelles, such as the cytoskeleton, which mulation of glycogen during glucose starvation, and by stain- plays an integral role in cell movement and signaling. Age- ing old cells trapped in our microfluidic device, we find that related changes in the cytoskeletal system make it a great glycogen content increases with age. We see that overex- point of interest in age-related studies. However, its roles in pression of the glycogen catabolism gene glycogen phospho- aging and longevity are still largely unknown. We hypoth- rylase (Gph1) increases lifespan, indicating that the mecha- esized that alteration of the actin cytoskeleton results in an nisms underlying the detrimental effects of the Msn2-driven accumulation of age-related cellular pathologies. To test this age-associated transcriptional program may be driven, at least hypothesis, we examined cellular markers of aging in C. el- in part, by the build-up of glycogen in aged cells. Accumu- egans worms with deactivated actin proteins. The genes for lated glycogen is seen in the aged cells of a number of evolu- the cytoskeletal system are well conserved between humans tionarily distant species including bacteria and human brain and Caenorhabditis elegans, making it a great and popular tissue and is implicated in multiple human diseases. Thus, model system for examining the role of the cytoskeleton in our work may elucidate the details of a fundamental frailty of aging. We used RNA interference (RNAi) to knock down the the metabolic network during aging. expression of cytoskeletal actins in the worms. Afterwards, we used fluorescent microscopy to examine markers of cel- POSTER SESSION 3 lular aging: pH, nucleoskeleton integrity morphology, and mitochondrial network morphology. We have found that per- MGH 241, Easel 146 turbation of actin cytoskeleton partially mimics age-related 2:30 PM to 4:00 PM cellular changes. We expect the results to be of help in the Rapamycin and Acarbose Prevent Fat Accumulation in ongoing study of the role of the cellular cytoskeletal complex Adult Mice Fed a High-Fat Diet in the human aging process. Nicole R. Tatom, Senior, Microbiology, Biochemistry Mentor: Matt Kaeberlein, Pathology POSTER SESSION 3 Mentor: Alessandro Bitto, Pathology MGH 241, Easel 147 The obesity epidemic has been a growing problem in the de- 2:30 PM to 4:00 PM veloped world and contributes to morbidity and early mor- tality of a growing number of individuals. Rapamycin is a Age Associated Activation of Msn2 Drives a Pathological FDA-approved drug used to prevent transplant rejection and Glucose Starvation Response to treat certain forms of cancer. Further studies have shown Yen Chi (Travis) Feng, Senior, Biochemistry rapamycin to increase life span in mice and reduce accumu- Mary Gates Scholar lation of white apidose tissue. However, long-term use of Mentor: Matt Kaeberlein, Pathology rapamycin can cause glucose intolerance and insulin resis- Mentor: Kenneth Chen, Genome Sciences tance. Acarbose is a FDA-approved drug for the treatment As the average population lifespan increases in many coun- and management of glucose intolerance in type II diabetes. tries, study into age-associated diseases and the basic biology The goal of this experiment is to determine if a combina- of aging has become even more important. Studying age- tion of rapamycin and acarbose have a synergistic effect on associated changes and lifespan-altering genes in the bud- fat accumulation and metabolism of mice fed a high fat diet. ding yeast has revealed fundamental insights into the aging To study the effects; 66 9-month-old mice were fed either a process. To measure replicative lifespan of budding yeast low (11%) or high (66%) fat diet and treated with rapamycin, cells, we image hundreds of isolated yeast cells trapped in acarbose, or a combination thereof. Weights, food consump- a microfluidic device over the aging process. Using flu- tion, fasting blood glucose, and body composition were mea- orescently labeled strains allows the measurement of pro- sured before onset of treatment and then regularly for 6 weeks tein expression and localization during aging.We observe of treatment. At the end of this period, the mice were sacri- that Msn2, a general stress-response transcription factor, be- ficed, and the tissues were collected for further analysis. Pre- comes increasingly activated with age in the budding yeast. liminary results confirm that mice treated with rapamycin did Paradoxically, knockout of Msn2 and its homolog Msn4 re- in fact gain less weight than those without drug intervention sults in increased lifespan, indicating that the Msn2-driven or with acarbose alone. The combination of both treatments transcriptional stress response is detrimental to longevity. did not have additive effects on weight gain, even though it

5 specifically reduced the accumulation of fat mass more than What Can the James Webb Space Telescope Tell Us either treatment alone in female mice. We are further investi- about the Dark Matter Halos of the First Galaxies? gating the effects of rapamycin and acarbose on weight gain Eden Faith Harris, Junior, Environmental Science & and body composition by conducting post mortem analyses Resource Management including the composition of the caecal microbiome, tissue Mentor: Matthew McQuinn, Astronomy histopathology, activation fat metabolism, and mitochondrial The formation of the universe’s first galaxies is currently not uncoupling in white adipose tissue. well understood; with the launch of the James Webb Space Telescope (JWST) in the near future, however, it may soon POSTER SESSION 3 be possible to uncover critical details about how and when the first galaxies formed. In this project, we examine whether it MGH 241, Easel 148 will be possible to discern the clustering of high-mass, high- 2:30 PM to 4:00 PM redshift dark matter halos from background noise when look- ing at data from the JWST. The ability to detect these halos, A Screen for Differential Responses to mTOR Inhibitor which are believed to play a key role in galaxy formation, Compounds among Wild and Domesticated Yeast Priya Anita Uppal, Senior, Biology (General), International through their clustering could lead to further breakthroughs Studies in the study of the early universe. An initial test of the effects Mary Gates Scholar, UW Honors Program of projection was run using data from the Illustris simulation Katherine Ann (Katie) Grayden, Senior, Biochemistry at redshifts z=6 and z=10. Halo positions were analyzed in Yordan (Jordan) Elala, Junior, Pre-Sciences both 3D and 2D at each redshift in order to determine how Mentor: Matt Kaeberlein, Pathology much projection altered our ability to detect halo clustering. Mentor: Mitchell Lee, Pathology When viewing 2D projections of halo positions, it became ev- ident that projection was significantly reducing our ability to Aging is a major risk factor for the most common causes detect clustering. When we made use of the third dimension of death in the developed world which include cancer, heart to eliminate the projection effect, the clustering of high-mass, disease, and neurological disorders. Because of this, thera- high-redshift halos become apparent at both redshifts. In re- pies that target the hallmarks of aging are a promising area ality, it will not be possible to replicate this 3D case; exact of study. The mechanistic target of rapamycin (mTOR) ki- measurements for the depths of high-redshift galaxies are not nase is a major regulator of growth, aging, and survival in obtainable using the JWST. Going forward, we will work to cells. Inhibition of the mTOR signaling pathway is associ- refine our results by applying real JWST data specifications ated with increased longevity in organisms including yeast, in order to determine the feasibility of using JWST data to worms, fruit flies, and mice. Inhibition of mTOR detect early halo clustering. Making use of information such can be achieved through pharmacologic intervention, which as limits on the detectability of galaxies based on their star is a promising strategy to extend healthy lifespan. To bet- formation rates and the uncertainty of JWST spectroscopic ter understand how mTOR inhibitor response varies between measurements will allow us to better determine whether the genetically-diverse populations, we utilized a set of 90 wild idea of studying halo clustering at high redshifts using JWST and domesticated yeast strains. We tested a set of mTOR in- data is worth pursuing. hibitory compounds on these strains to identify strains with increased sensitivity or resistance to mTOR inhibition. We have identified genetic variants that drive drug sensitivity or POSTER SESSION 3 resistance in these strains. We then engineered mutations Commons East, Easel 83 into laboratory strains to confirm that these mutations reca- 2:30 PM to 4:00 PM pitulate the phenotype of interest. By understanding drug re- sponse across genetically-diverse populations, we will create Cross-Correlations between Lyman Alpha and Lyman the framework for a precision medicine approach to develop- Beta from the XQ-100 Legacy Survey ing healthspan-enhancing compounds that can be translated Bayu Jarod Wilson, Senior, Physics: Comprehensive to humans. Physics, Astronomy Mary Gates Scholar Mentor: Matthew McQuinn, Astronomy POSTER SESSION 3 Mentor: Vid Irsic, Department of Astronomy Commons East, Easel 82 Radiation emitted from supermassive black holes in the early 2:30 PM to 4:00 PM universe (quasars) is absorbed by hydrogen in the intergalac- tic medium. Hydrogen absorbs light at certain resonant fre- quencies in the spectra of quasars. Statistics of Lyman-alpha

6 absorption (the most studied resonant frequency of hydrogen) the from head to tail. The appearance of alae has been probes the cosmological parameters governing the universe observed to be different in our AD model mutants, indicat- (e.g. mass of dark matter) and the temperature of intergalactic ing that ECV signaling has been disrupted. Using these AD- gas (which constrains how the universe was heated). To fur- model mutants, we aim to establish these novel phenotypes as ther improve these constraints, I will be using another Lyman a means to further investigate the physiological consequences series transition (Lyman-beta). Due to the smaller absorption of AD-associated toxic peptide expression. cross-section of Lyman-beta, we may probe higher densities than measured with the Lyman-alpha transition therefore in- creasing the number of data points to analyze. By including POSTER SESSION 4 the Lyman-beta transition, our analysis allows for a better un- MGH 241, Easel 146 derstanding of intergalactic gas which provides for more ro- 4:00 PM to 6:00 PM bust cosmological constraints. Cell Cycle Control Mechanism Against Fatal Genomic Missegregations in Aging Yeast POSTER SESSION 3 Mung Gi (David) Hong, Senior, Public Health-Global MGH 206, Easel 172 Health 2:30 PM to 4:00 PM Joslyn Erika Goings, Senior, Biology (Physiology) Mentor: Matthew Crane, Pathology Healthspan Metrics for Uncovering the Physiological Impacts of Alzheimer’s Disease in C. elegans Cell divisions require proper replication and distribution of Franklin Xavier Faust, Senior, Neurobiology genetic materials between mother and daughter cells, and UW Honors Program mistakes made during the process may result in aneuploidy Tyler J Schmitz, Senior, Biology (Physiology) (abnormal number of chromosomes in a cell) and possible Rahul Kishore (Rahul) Chaliparambil, Senior, carcinogenesis. Thus, checkpoints exist along the cell cy- Mentor: Josh Russell, Pathology cle to ensure that cellular errors are corrected. Likewise, Mentor: Matt Kaeberlein, Pathology during the mitotic processes of budding yeast, Saccaromyces Mentor: Alexander Mendenhall, Pathology cerevisiae, numerous checkpoint mechanisms evolved to pre- vent catastrophic genomic missegregations. By observing C. elegans is a prolific model organism that is well estab- the replicative life span of aging yeasts fluorescently tagged lished in the field of aging research and age-related diseases. with histone 2B through single cell imaging, we identified a C. elegans can be genetically manipulated to express human new mechanism that is needed in aging cells for correcting toxic proteins associated with neurodegenerative diseases. Its nuclear missegregation. This Retrograde Transport Nuclear amenability to genetic screening and short lifespan make it (RETRN) pathway fixes genomic missegregation by delay- an ideal animal model for studying the genetic basis for the ing the incorrect mitotic division and returning the genetic neurological health-declines associated with Alzheimer’s dis- material from the daughter to the mother cell. Following the ease (AD). Here we introduce new experimental approaches correction, mother cells could continue to divide and pro- for quantifying the organism-wide impacts of nervous sys- duce healthy daughter cells. In our research, we generated tem specific expression of human AD-associated toxic pro- new strains of mutant yeasts that underwent incorrect mi- teins.. The pharynx in C. elegans is an oral pumping struc- totic divisions to further observe the activation of the RETRN ture used in feeding. The pharyngeal nervous system, com- mechanism. Each mutant strain had different non-essential prised of only twenty neurons, dictates the rate of pharynx genes relevant to the cell cycle deleted. We confirmed the pumping in the animal. Pharyngeal pumping rates have been genetic makeup of each mutant strain through replica plating shown to change and decay with the age of the animal, mak- and PCR. Then, we imaged mother cells from verified mu- ing it an ideal metric in aging research. The frequency of tant strains and observed the budding events throughout their pharynx pumping can be measured via an electrophysiologi- lifespans. This allowed us to see specific points along the cal recording of the pharynx’s contractions. We plan to use lifespan where mitotic divisions occurred, and whether the this electropharyngeogram (EPG) as a measure of neurode- deletions affected the RETRN pathway. We have speculated generation to compare wildtype animals with our AD-model that this mechanism is a result of cellular damage due to in- mutants. Furthermore, the proper function of extracellular creasing genomic instability in aging cells, and thus is rarely vesicles (ECVs) are thought to be important in the clearance observed in young, healthy cells. The RETRN pathway could of toxic peptides associated with AD. The only reported phe- be part of many new pathways needed when cells age and notype for ECV signaling is the differential development of become genomically unstable. Since mammalian cells also the cuticle, the animal’s outer-most layer of epidermis. The become genomically unstable with age, similar mechanisms cuticle’s formation can be assessed through the appearance of may be necessary for age-associated genomic instability in the worm’s alae, a set of three lateral stripes running across multicellular eukaryotes.

7 Development and Testing of WRANGLER for Design POSTER SESSION 4 and Modeling of Peptides and Proteins with Interactive MGH 258, Easel 187 Visual Analytics Jennifer Ann (Jenny) Ferina, Senior, Bioengineering 4:00 PM to 6:00 PM UW Honors Program Novelty Not Disparity - Body Shape Evolution in Marine Mentor: Valerie Daggett, Bioengineering and Freshwater Needlefishes Mentor: Matthew Childers, Bioengineering Justin Yi Kai Ng, Senior, Aquatic & Fishery Sciences Computational simulations of protein dynamics provide an Mary Gates Scholar efficient way of predicting protein behavior and are increas- Mentor: Matthew Kolmann, Friday Harbor Labs ingly being applied to peptide and protein design. However, The Neotropics hold the greatest diversity of fishes, with design tools and software focus on static structures. Incor- South America alone hosting around 25% of global fish bio- poration of dynamics directly or through design libraries de- diversity. Despite presumably fierce competition with en- rived from dynamics simulations allows the user to focus on trenched primary freshwater fishes like otophysans, South optimization of the native dynamics of the protein for a spe- America is also home to a conspicuously high number of cific purpose. Critical libraries for design, such as side chain marine-derived lineages (MDLs), freshwater taxa which have rotamer libraries and amino acid propensities are typically de- evolved from marine ancestors. Transitions from marine to rived from static structures, which do not reflect behavior in freshwater may have catalyzed ecological opportunity and dynamic conditions. Therefore, including rotamers and con- are apt systems for examining whether habitat transitions formational propensities derived from behavior during pro- prompt ecomorphological diversification. Body-shape and tein simulations in molecular modeling and design software size correlate with many aspects of ecology and life his- should improve the design process and outcome, particularly tory: foraging through locomotion and feeding morphol- for peptides. Additionally, current software does not allow ogy, reproduction by predicting offspring size and number, the user to adjust the main chain dihedral angles of the back- and more generally, larger fishes generally occupy higher bone according to Ramachandran plots reflecting the unique trophic niches. We examined how such an ecological transi- free energy landscape of each residue. The WRANGLER tion has affected the body-shape diversity of tropical needle- software was designed in order to include dynamic data to fishes and sauries (Beloniformes). Using micro-computed to- better model and design against and for dynamic systems. mographic (µCT) scanning, geometric morphometrics, and A number of libraries derived from dynamics simulations of phylogenetic comparative methods we examined body-shape all known protein folds have been incorporated. In addition, evolution in 33 species of belonids and two scomberesocids. the software is interactive with a graphical interface to easily We examined the evolutionary pattern and tempo of body- change and visualize geometries and analyze peptide/protein shape evolution in Asian and South American beloniforms properties. WRANGLER was evaluated based on ability to using a published molecular phylogeny,. The primary axis facilitate design of several amyloid peptide aggregation in- of body shape variation is elongation/truncation, driven by hibitors. Resulting designs were evaluated through molecular lengthening/shortening of either the rostral or trunk regions. dynamics simulations for their secondary structure retention We also find that freshwater taxa are generally smaller than and physical properties. Control amyloid peptide aggrega- their marine counterparts, and become reduced in size ei- tion inhibitors were included that have already been designed, ther through miniaturization (skeletal reduction) or dwarfism synthesized and tested experimentally in lab. Several pep- (skeletal loss). Despite morphological novelty in freshwa- tides designed in WRANGLER appear to be better than the ter belonids, our results show similar levels of body shape controls by a variety of metrics. The next step is to synthe- diversity between marine and freshwater taxa. Despite simi- size these new designs and test them against the amyloid-beta lar disparity between marine and freshwater taxa, freshwater peptide associated with Alzheimer’s Disease to see if they belonids occupy a surprisingly large region of morphospace outperform our current compounds. considering their relatively low species richness. POSTER SESSION 4 POSTER SESSION 4 Balcony, Easel 111 MGH 206, Easel 176 4:00 PM to 6:00 PM 4:00 PM to 6:00 PM

8 Characterization of Cell-to-Cell Gene Expression Variation Within Tissues of Aging C. elegans Anthony Terrell Reynolds, Senior, Biology (Molecular, Cellular & Developmental), Microbiology Mentor: Nikolay Burnaevskiy, Pathology Mentor: Matt Kaeberlein, Pathology

Aging is characterized by the increasing loss of physiological and cellular functionality, however the mechanism that un- derlies this deterioration is still unclear. Emerging evidence indicates that aging is associated with increased cell-to-cell variation in gene expression within tissues: homologous cells within tissues express the same gene at varying levels. The causes of this age-related variation of gene expression are not known. Here we aim to investigate the mechanisms of in- creased cell-to-cell variation in gene expression with age us- ing C. elegans as a model system. By characterizing aging in C. elegans, we hope to provide further insight into the molec- ular characteristics of aging in humans, and possible points of intervention. We hypothesize that stochastic noise of tran- scription can lead to increased gene expression variation with age. Previously we have found that stochastic noise of gene expression is incredibly restricted in young C. elegans ani- mals. Using quantitative fluorescent microscopy we have an- alyzed expression of reporter genes in old animals and have dissected the potential contribution of stochastic transcription noise into age-related variation of gene expression.

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