In a world of childhood obesity, soaring gas prices and climate instability, bicycles are quickly becoming a socially, environmentally and economically sustainable alternative to single occupancy vehicles. In May, I will be organizing chaperoned bike-trains for elementary school children in Wedgwood and Thornton Creek elementary schools, with the intention of increasing the number of children commuting by bicycle. A bike-train is comprised of elementary school children and adult chaperones riding safe and efficient pre-determined routes to school. Children learn bicycle safety, rules of the road, and riding etiquette, all while acquiring social and communication skills, as well as physical confidence. These rides also build community among adults, as chaperoning, organizing and discovering shared passions are all part of this process. While implementing bike-trains is a small-scale project, it addresses the most pressing issues of our day: health concerns, social isolation and environmental degradation. This project will examine two methods of organized bike-trains:  traditional, multi-stop routes in at Thornton Creek Elementary, and a more casual "meet and ride" route at Wedgwood Elementary. With the culmination of this project, I will compare the outcomes of both methods of bike-trains, compiling my research into a document enabling parents, teachers and staff throughout Seattle schools - and potentially worldwide - to implement bike-trains in their communities. Bike-trains, an experiment in applied research, cultivate local solutions to current global concerns.

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 of individual CNVs may give insight to the origin of schizophrenia. We focused on a CNV present in a patient with early onset schizophrenia. This mutation 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 in the patient’s lymphoblasts that we predict will result in aberrant, truncated DCUN1D5 protein. To test the conformational stability of these aberrant proteins, we then expressed epitope-tagged full length and truncated DCUN1D5 in HEK293 cell lines. These transfected cells also allow us to study the functional capabilities of the aberrant proteins in the cullin neddylation pathway, and the specific cullin binding partners of DCUN1D5. Investigation of these aberrant proteins and their function may shed light on pathways that contribute to schizophrenia, potentially guiding the search for new candidate genes and the development of novel treatment strategies.

Schizophrenia is a debilitating neuropsychiatric disorder with a worldwide prevalence of 1%. Although the heritability of schizophrenia is high, there is a large proportion of affected individuals with no family history. We are testing the hypothesis that many different severe mutations are the causal genetic factors for schizophrenia. In order to test our hypothesis, we sequenced the exomes of approximately 50 trios consisting of an affected individual and his/her parents who are free of mental illness. Exome sequencing is a rapid and robust method for looking at only coding portions of the genome, and allows for the detection of rare variants in those regions. Sequence data is then run through several bioinformatics filters to ensure that the variant is not common in the general population, and that the variant is probably damaging to the gene product. All variants that pass through the bioinformatics filters are validated with Sanger sequencing. De novo mutations were found in 19 different genes in 11 trios. Of the mutations 13 were single base pair changes, and 6 were truncating nonsense or insertion/deletion events. After these experiments have been carried out on approximately 100 trios, we will use the group of candidate genes to identify critical pathways that may be affected in schizophrenia. Understanding the structure of these pathways may allow for the development of targeted therapies for schizophrenia.

The level of peer substance use is one of the best predictors of an adolescent's own substance use. In addition, impulsivity, the tendency to engage in risky behavior, is associated with higher levels of substance use in adolescents. The goal of this study is to investigate the relationship between peer substance use, individual and peer impulsivity, and individual substance use. Data from the National Longitudinal Study of Adolescent Health, a nationally representative sample of adolescents will be analyzed. Two sets of analyses will be performed. The first set of analyses uses a 3-level multiple membership model to assess the associations between individual and peer substance use, impulsivity and measures of social status. The second set of analyses employ relational analysis to assess the probability of an individual with a given level of substance use and impulsivity to be a friend of another individual with a certain level of substance use and impulsivity. We predict that for the first set of analyses, that the association of peer substance use on individual substance use will be significant, and moderated by the individual's impulsivity. Additionally, we predict that peer substance use's effect will be attenuated by individual substance use over time. For the second set of analyses we predict that adolescents similar in substance use and impulsivity are more likely to be friends than those adolescents who are dissimilar in substance use and impulsivity. The predicted results would suggest that the mechanisms of both peer influence and peer selection are playing a role in the trajectory of substance use. That is, substance using adolescents select peers that have similar levels of substance use, who then influence them to continue or escalate substance use. The results of this study will suggest social mechanisms that influence substance use, and suggest effective peer based interventions.

In 1986, the United States’ Centers for Disease Control and Prevention (CDC) established the Gonococcal Isolate Surveillance Project (GISP) to monitor the trends of increasing antimicrobial resistance of urethral Neisseria gonorrhoeae isolates from men who have sex with men (MSM). Since then, such strains of N. gonorrhoeae, the bacterium that causes gonorrhea, have been observed to repeatedly develop resistance to antimicrobials including sulfonamides, penicillin, tetracyclines, and most recently, fluoroquinolones. The effectiveness of the cephalosporins, the last remaining option for empirical first-line treatment of gonorrhea, is threatened by declining gonococcal susceptibility to cephalosporins in the US and worldwide. In correlation with the University of Washington Neisseria Reference Laboratory, N. gonorrhoeae isolates recovered from non-urethral sites were screened for antimicrobial resistance, in an attempt to identify these previously unmonitored trends. Prior to this, there was no data concerning antimicrobial resistance trends of extra-genital N. gonorrhoeae isolates. The experimental approach employed was disk diffusion of cefpodoxime (cephalosporin) and azithromycin (macrolide). Diameters of zones of inhibited growth, which can be seen directly on agar plates, were measured. Analysis of results was visual, and it was often clear whether or not an isolate was resistant to an antimicrobial agent. By observing non-urethral isolates, information is gained regarding the management and treatment of gonorrhea based on other anatomical sites. Experimental analysis spanning two years of isolates (2008-2009) suggests similar susceptibility trends when compared to prior GISP data. While more exact trends will be determined based on a longer span of time, totaling ten years, completion of this work will inform treatment guidelines that consider a larger variety of N. gonorrhoeae isolates.