Adrenergic receptors, a family of G-protein coupled receptors, are a common target by pharmaceutical drugs for cardiovascular disease. With cardiovascular disease being the leading cause of death in the United States, adrenergic receptor targeting drugs are increasing in use. Phenylephrine has long been known to be an agonist of the specific α-1 adrenergic receptor. Past research shows that cancer cells do not contain α-1 adrenergic receptors. Although, using dynamic mass redistribution (DMR), when we introduced U251 human glioma cells to increasing concentrations of phenylephrine, we found evidence of a conformational change in the U251 cells. Other adrenergic receptor agonists (norepinephrine, isoproterenol, and clonidine) exhibited a similar response. This suggests that U251 cells may have α-1 adrenergic receptors. We hypothesize that U251 glioma cells exhibit a structural change in the presence of phenylephrine because they contain α-adrenergic receptors that recognize the ligand and trigger a cellular response. The effects of phenylephrine on U251 cancer cell viability and cell proliferation is still unknown, allowing for a possible future in generating therapies to combat cancer.

Anterior cervical discectomy and fusion (ACDF) is a well-established surgical technique used for the treatment of various disorders of the cervical spine. The two most common ACDF procedure methods are: standalone systems and traditional plating techniques. Dysphagia, the inability to properly swallow, is an extensively described complication; it has been proposed that mechanical irritation, additional dissection, or displacement of the esophagus by plate placement may contribute to a greater incidence of postoperative dysphagia. The aim of this retrospective cohort study is to assess differences in pain, clinical outcomes, and dysphagia, including complication and readmission rates, following ACDF using either a standalone cage system or a cage with anterior plating (traditional plating). Between 2014 and 2015 we identified 377 consecutive patients meeting study criteria (standalone, n= 211; plate and cage, n= 166). Pre-operatively scores were collected for patient specific characteristics, surgical characteristics, and Numeric Pain Rating Scale (NRS). In addition, complication and readmission rates, the Dysphagia Disability Index (DDI), and NRS scores were collected at one year and two years post-operatively. There was significantly greater improvement in neck pain scores for the plate and cage group after one and two years post-surgery ( 2.3 and 3.1 versus 1.6 and 1.5, respectively; p <0.01). This could presumably result from biomechanical advantages when compared to stand-alone cage systems. There was no statistical difference between DDI scores either postoperatively or at two years post-surgery. These results indicate that mechanical irritation may not differ between procedure types. Further research is needed in order to determine factors that may lead to a higher rate of nonunion for patients undergoing standalone cage placement. 

Approximately 40% of over-the-counter drugs target G protein-coupled receptors (GPCRs), which are seven-transmembrane proteins that become activated when drugs, hormones, or neurotransmitters bind to the receptor. One class of GPCRs, known as adrenergic receptors (ARs), are highly targeted by the endogenous catecholamines, epinephrine and norepinephrine. ARs are comprised of three unique subtypes: α1ARs, α2ARs, and βARs. Focusing on the α1ARs, the different types are α1A, α1B, and α1D. In cancer biology, most research has focused on βARs since many people take medications that specifically target βARs. In my research, I focus on α1BARs due to a recent publication of The Hague Lab, which recently discovered α1BARs in colorectal cancer cells. Reading this publication led me to search for α1BARs in various cancer cell lines by using the Label Free Dynamic Mass Redistribution (EPIC-DMR) method. After adding specific drugs, the EPIC-DMR tracks any conformational change of individual cells to indicate the cellular response to the drugs. Using this method, I discovered α1ARs are present in HCT116 cells, a colorectal cancer cell line. In the future, I intend to determine the α1AR subtype by performing radio-ligand binding, using Quantitative Real-Time Polymerase Chain Reaction (QRT-PCR), and looking at agonist and antagonist responses. This discovery could potentially play an important role in therapeutic drug development for many cancer patients.

The Westphalian state system—i.e., the global division of power in to roughly 195 sovereign nation-states—is proving inadequate in the face of rapid globalization. As our world becomes increasingly integrated, the political tools of the past, which uphold division and absolute autonomy, cannot offer a viable vision for the future. This is particularly salient in the case of global climate change: our commitment to statehood and international competition is preventing us from seeing the ways in which we are deeply interconnected, effectively imperiling current and future generations. Indeed, how should we respond to the 200-250 million climate refugees that will be displaced in the next 50-70 years due to climate change? What duties of justice are they owed? In this project, I assess the social contract tradition in political theory which offers the main philosophical grounds for the contemporary state system. I argue that, for a number of different reasons, social contract theory fails to offer a desirable framework for the new global political order necessitated by globalization. A theoretical framework that recognizes the ways in which humans are fundamentally in nature, and thus widens the scope of justice, offers a more promising alternative for regulating global cooperation. Indeed, if we, the human race, see ourselves as a unified group playing a small part in the larger play that is the global ecosystem, then our vision will clear and we will begin to see the appropriate duties of justice that we owe to each other, nonhuman animals, and nature.

Adverse Events (AEs) are detrimental medical incidents in a research participant that may or may not be related to the investigational agent. During clinical trials, physicians are required to document attribution of AEs with limited guidance regarding how to assign attribution. The objective of this study was to determine the accuracy of physician based attributions for AEs occurring in cystic fibrosis (CF) patients participating in blinded randomized controlled trials (RCTs). This retrospective study pooled clinical trial data from 4 CF RCTs; all participants who experienced ≥1 AE were included. A repeated measures logistic regression model using generalized estimating equations and adjusted for baseline demographic variables (gender, age, CF genotype), comorbidities, and lung function (forced expiratory volume in one second; FEV1). The primary predictor of interest was receipt of study drug versus placebo. The primary outcome of interest was physicians’ determination of the AE as related to study drug. Study patients were young with mild lung disease. Receipt of study drug was not significantly associated with the likelihood a physician would deem an AE to be related to study drug. However, we found significant associations between age, gender, and FEV1 and our outcome of interest– presence of an AE felt by a physician to be related to study drug. These findings suggest a biased assessment of physician attribution. Physician assessment of relatedness in RCT’s is a key requirement per the Food and Drug Administration (FDA). We found no significant association between AEs coded as related to study drug and actual study drug receipt. Interestingly, we found other associations implying an intrinsic bias in physician assessment based on age, gender and disease severity. Further research may clarify whether changes are needed to current FDA guidelines.

Kidney cancer is the 7th and 10th most common cancer in men and women in the United States respectively. Renal cell carcinoma (RCC), a cancer of the proximal convoluted tubule, accounts for >90% of these kidney cancer incidences. Most cancers, including RCC, stimulate angiogenesis – the sprouting of existing blood vessels. By upregulating the expression of angiogenic factors, such as vascular endothelial growth factor (VEGF), tumors promote vascular sprouting within their microenvironment. This increased vasculature allows for increased oxygen transport as well as an opportunity to metastasize. This tumor-induced angiogenesis is of particular interest to researchers hoping to continue to develop alternative cancer therapeutics to inhibit angiogenesis, starving the tumor of oxygen, or normalize the vasculature, making drug delivery more effective. Common cancer models like 2D cell cultures and animal xenografts have been shown to be poor predictors of drug efficacy in patients. A lack of cellular complexity in 2D cultures along with genetic differences in animal xenografts make them insufficient models of the human pathophysiology seen in vivo. To address this problem, we are developing a 3D, vascularized, flow directed, microphysiological device deemed a “kidney-tumor-on-a-chip”. To engineer a perfusable microvessel, a 120μm collagen channel was lined with human umbilical vein endothelial cells (HUVECs). Primary RCC spheroids that mimic the 3D structure of solid tumors were then introduced into the surrounding collagen, recapitulating the tumor-vessel microenvironment. Initial results have shown no endothelial sprouting in non-RCC control devices, compared to significant endothelial sprouting in devices with RCC spheroids. These results suggest RCC cells may contribute to angiogenic sprouting in our microphysiological device, simulating what is observed in vivo. The ability of this kidney-tumor-on-a-chip to mimic the tumor-vessel microenvironment demonstrates its potential to be a more effective cancer model for drug testing.

Airborne and satellite remote-sensing surveys of Antarctica have revealed over 400 subglacial lakes beneath the ice sheet. These lakes are one component of a subglacial hydrology network that also includes drainage channels, swamps, and estuaries. The influence of this subglacial hydrology network on ice-sheet dynamics is unclear. Water under ice sheets can reduce friction at the ice-sheet base, and thereby increase ice velocity. Alternatively, partitioning of water into lakes or channels, can also limit the area lubricated by water, and thereby decrease ice velocity. Ice-penetrating radar can map the presence of subglacial water due to the differing electrical properties of an ice/water vs. ice/sediment (or rock) interface at the ice sheet bed. The radar surveys also map constant time (isochronal) layers within the ice sheet that are formed due to chemical (and thus also electrical) differences in the snow deposited at the ice-sheet surface, which is eventually compressed into ice. Burial by subsequent snowfall and ice flow deforms these layers, which were originally surface parallel. Thus mapping these layers reveals the internal stress state and flow history of the ice. Here we report on the internal architecture of the ice sheet in the vicinity of Subglacial Lake Whillans, West Antarctica, as imaged by ice-penetrating radar. In the 2010-2011 austral summer, 500 line kilometers of ice-penetrating radar data were collected over Subglacial Lake Whillans in support of subglacial lake access drilling. In radar profiles (2-dimensional cross sections through the ice), we trace isochronal, internal layers imaged by the radar. Compared to nearby grounded areas, layers in the ice over the lake are highly deformed, suggesting ice-flow disruption over the lake. This interpretation is consistent with the active nature of the lake, which fills and drains every few years, causing changes in friction at the ice-sheet base, and thus non-steady ice flow.

In Kenyan HIV-1 infected children, it is likely that exposure to household indoor air pollution (HAP) increases susceptibility to respiratory illness, cancer, growth failure, and compromised cognitive abilities. Kenyan families usually live in one-room houses and use wood or charcoal cook stoves indoors. Smoke from burning of wood and charcoal contains large quantities of polycyclic aromatic hydrocarbons (PAHs) which are among the many components of incomplete combustion. Many PAHs are carcinogens that undergo metabolism and are excreted in urine. In order to assess children’s exposure to wood and charcoal smoke, single spot urine samples were collected from 100 subjects: 50 recently diagnosed HIV-1 infected children, age-matched healthy HIV uninfected children, and their mothers. Urine samples were hydrolyzed by treatment with glucuronidase enzyme and cleaned up with solid phase extraction. High-performance liquid chromatography with fluorescence detection was used to analyze the samples for PAH metabolites. We anticipate that urinary hydroxyl PAH metabolite concentrations will be high in these cohorts of HIV-1 infected and healthy children reflecting the exposure to HAP by use of wood and charcoal for cooking. Findings of this research will help to understand the pathogenesis of cancer and respiratory diseases in HIV-1 infected children, healthy children, and their mothers.

This project focuses on adding unique telemetry and communication capability to one of the largest and fastest growing areas in the Washington State aerospace industry: Unmanned Aerial Systems (UAS). These systems have the potential to revolutionize a wide variety of commercial applications such as precision agriculture, disaster management, mapping, and ecological/biological monitoring and represents a $13.6 billion civilian market. One of the main challenges for UAS integration is to provide reliable and effective guarantees for safe operation that in turn requires high-performance and flexible control/navigation of the aircraft and reliable transmission modes from air to a ground control station or operator. For example, a typical commercially available UAV will have 3 distinct sensor-processing-radio chains, one each for onboard camera, one for data telemetry (navigation and strategic command) and one for primary command & control data. This effort fundamentally seeks to mature ongoing work at UW and will allow for greater communication bandwidth, enhanced flexibility, and levels of control between the UAS and GCS and achieve the required situational awareness as mandated for UAS operations. The outcome of this project will be a modular, encapsulated radio system that can be used to combine the myriad data links between a UAS and the GCS into a single, robust, and reconfigurable link. The link quality will be tested using a bladeRF software defined radio paired with a student built, Pixhawk based octocopter. Several flights tests will be conducted by students using custom built software which will measure the strength of the UAV based link in various environments. This project encapsulates the construction of the octocopter, the build of the software defined radio system, and flight testing. A publicly accessible link quality database will be populated with fight test data in order to encourage further development of software defined based communication links.

Working memory is a cognitive skill that allows temporary storage and manipulation of information. It is an important skill as previous studies have shown relations between working memory and various cognitive abilities, such as reading comprehension and speech perception. So far, evidence have suggested that working memory can be enhanced with training. One of the training experiences that has been extensively researched is early music training. Most studies have shown that music training experience has a positive correlation with working memory while other studies has shown no difference in working memory capacity for musicians and non-musicians. For this study, our aim is to further delve into this controversial topic and seek more information and data to find out whether early music training could enhance working memory. We recruited a group of musicians (N=20) and non-musicians (N=20) and compared working memory capacities between the two groups with two tasks: Memory Updating and Operation Span, targeting slightly different aspects of working memory. We hypothesized that those who had early music training would have higher scores on both tasks. Data analysis has been completed and the initial results from the data shows that there is no significant difference in working memory capacity between musicians and non-musicians. Currently, further analysis of data is still ongoing to help understand the results we observed. We will be discussing the similarities and differences of the tasks compared to previously published studies and how our results contribute to this field. 

Many scholars have constantly claimed that a shift from defined benefit plans to defined contribution plans has been the wrong course of action in policy and it has brought direr effect to the economy. Economists have argued that defined contribution plans are generating inefficiency pension income for employees in the private sectors, creating further cost burden for taxpayers and discouraging employees to stay at a job. While most observers are accepting the current situation by sticking to the traditional defined benefit plans, there are significant indicators in which the shift to defined contribution plans is inevitable. Economic shocks such as financial crisis, new health policy like Affordable Care Act and Congress abolishment of the Aid to Families with Dependent Children federal assistance program have changed the tides. They have brought a great deal of attention on how defined contribution pension plans can shape agents’ behavior in the labor market. Using datasets from the Survey of Income and Program Participation (SIPP) Synthetic Beta file and the National Quarterly Workforce Indicators, this paper examines the proposition that defined contribution plans motivate newly hired workers to stay at a job for a much longer period and gain higher weeks at pay without federal assistance programs taken place. This occurs particularly for male employees in public sectors. Regression analysis (OLS and logistic) demonstrates that workers enrolled in defined contribution pension plans have increasing personal level annual earnings taxed under FICA, higher probability in having employer- based health insurance and a larger family size in their individual households. Furthermore, this paper attempts to explain whether defined contribution plans have transitory or permeant effect on workers’ wellbeing during economic shocks using unit root test to determine whether there exists a stochastic trend.

Keywords: defined contribution pension plans, labor market, individual households, workers

Cultural festivals provide the opportunity to share and celebrate ideas, values, art, food, etc. from the heritage of other homelands. Aside from other smaller gatherings, these mass public festivities are typically held only once a year. With such a limited window for this type of cultural sharing, it is ideal that people of the represented community share fully their experiences of their culture and have the accommodating infrastructure to do so to increase cultural competency. Creating inclusionary spaces that allow cultural expression and celebration is termed cultural placemaking. After reviewing issues in Journal of Planning Education and Research from 2017-2010 I discovered that cultural placemaking was well intentioned but was not well reported or practiced. This is an issue when communities are projected to increase in density and in diversity. It is important for planners and city officials to know the significance of public spaces that allow for cultural expression in order to increase community development and cohesion as communities continue to grow. Through literature review, attending several festivals in Seattle, and interviews of students and festival participants, cultural festivals can provide a deeper understanding of culture instead of perpetuating stereotypes. The purpose of this project is to reintroduce the significance of cultural festivals to planners and city officials in the form of a white paper that also provides some suggestions to help local festival coordinators increase local participation, community support and create meaningful experiences for both visitors and people with cultural heritage.

There is a current lack of art and outdoor environmental education within the public school system. Outdoor education refers to any topic that is taught outside, while environmental education concerns the natural environment and issues that pertain to the natural environment. Students are often taught about the problems that deal with our environment, though they are rarely taught to simply appreciate it. Art can be used as a tool to give students enjoyable hands on environmental learning in an outdoor setting. By using photography students are able to interact with their environment, show others how they see the world, and feel a deeper sense of appreciation towards nature. This project was inspired by the Literacy Through Photography program at Duke University and will address the question of how photography in an outdoor curriculum can increase a student’s environmental awareness within public schools. To begin answering this question I have compiled a comprehensive literature review and taught a pilot curriculum activity with a K/1 class at Leschi Elementary School that incorporates being outdoors, the environment, and photography. Preliminary literature review and observation results suggest that students enjoy interactive activities outside and that outdoor and environmental education is beneficial for student health, environmental awareness, and happiness. In the future, these findings could be studied further with more pilot programs in a variety of school locations, such as within intercity schools where nature is lacking.

Over the past ten years, esports, or competitive gaming, has come to the forefront of youth entertainment. In 2016, global awareness of esports surpassed 1 billion people. The largest segments of this population are college-age (18-25 years) and middle/high school-age (12-18 years). While significant activity is being undertaken by both universities and collegiate athletic conferences to develop varsity programs that structure the experience and growth of esports players, such efforts have not yet been made in high schools. My research clearly outlines the developmental impacts to students of varsity esports programs at the high school level. Based on the finding that such positive impacts scale directly with an administration’s support for the club, my paper provides recommendations on how administrators and teachers can support esports programs, even in the common case where esports is a foreign concept to staff. I draw on: 1) an extensive literature review synthesizing secondary research on the effects of participating in high school esports and ‘games in the classroom’ curricula, 2) programmatic recommendations based on analyses of similar extracurricular and youth development programs, and 3) observations and interviews with existing high school esports communities. The end goal of my research is to make high school esports a more productive developmental experience for high school students by de-stigmatizing and structuring participation. In addition, I highlight opportunities for further research into the mechanics and effects of high school esports programs.

Endothelial cells (ECs) are cells that line our blood vessel walls. They differ throughout the circulatory system. For example, high pressure arteries typically have tighter endothelial junctions/gaps than the leaky, low pressure veins. ECs are known to sense fluid shear stress and hydrostatic pressure. These cues play a large part in embryonic development of the vasculature and induce short term responses in adults, such as dilation and constriction of arterioles, but it is unknown if adult ECs adapt to them in the long term. This matters for many medical procedures, such as venous graft bypass surgery, where the saphenous vein is implanted to bypass a blocked artery. These grafts are often lifesaving successes, but they sometimes re-occlude. Venous and arterial endothelium are very distinct, and it is important to know if the venous ECs in the graft can adapt to their new arterial environment. If not, that could explain the pathological re-occlusion. Here, we measure adaptation by changes in gene expression from a venous to an arterial phenotype. We designed a novel in vitro pump system to expose a flow chamber with endothelial cells to controlled flow and pressure. HUVECs (human umbilical vein endothelial cells) were then cultured and seeded into the chamber. Finally, a quantitative real time polymerase chain reaction (qRT-PCR) will measure gene expression at various time points in the venous (20 cmH₂O, low flow) and arterial (60 cmH₂O, high flow) cases. We analyze the markers EphrinB4 (EphB4) (higher in veins), EphB2 (arteries), Cx40 (veins) and endomucin (arteries). We present preliminary gene expression data from the 24-hour time point. We hypothesized that HUVECs will respond to arterial conditions with increased arterial gene expression, while retaining their venous state in venous conditions. Supporting or falsifying this will illuminate endothelial cell response to changing conditions in the body.

For our Jackson School of International Studies capstone class, Task Force, we created a strategic communications plan tied with a digital story to create a social media campaign. The goal of this campaign is to communicate Tribal Treaty Rights between tribal and non-tribal millennials in the Puget Sound area. The Treaty Rights target issues in the Puget Sound caused by climate change, including decreasing salmon populations and managing non-tribal fishing rights around the region. Most millennials are unaware of these rights, or these issues in general, despite living in the Puget Sound. Our research, primarily self-hosted surveys and focus groups, show a trend in millennials to be sensitive to cultural diversity and climate change acceptance, making them a prime demographic for a marketing campaign. After data collection, we created social media groups, including Facebook, Instagram, and a digital story for potential use in the Tulalip Tribes website. We worked closely with the Tulalip Tribes in Marysville, and visited their location, supervised by Tulalip Tribes' Public Affairs Coordinator Francesca Hillery. UW campus resources will be invaluable in our pursuits; we will contact the school newspaper "The Daily", as well as collaborate with various departments, such as the Intellectual House, to spread awareness and to set up relevant lectures. Millennials are apt to be interested in this topic, therefore, one of our main campaign goals is to create the knowledge in the first place. If successful, our social media campaign will grow towards increasing implementaion on campus and for the tribes themselves. Overall, this can lead to future, independent student involvement and efforts to make a change for themselves, for the tribes, and for all in the Salish Sea region. 

Imidacloprid (IMI), a neonicotinoid, is being sought as an alternative to the carbamate pesticide, carbaryl, to control burrowing shrimp (ghost shrimp, Neotropea californiensis) in Willapa Bay and Grays Harbor. The shrimp destabilize sediments resulting in poor survival and low yields of the commercially harvested Pacific oyster. Previous laboratory tests indicate ghost shrimp are overtly affected (immobilized) when exposed to IMI at concentrations up to 1 million ppb in artificial seawater (SW), but not killed and subsequently recover. Our objective was to determine if emamectin benzoate (EB) is a better alternative to IMI. EB, the active ingredient (a.i.) in Slice(R), is currently registered for use in marine waters for the control of sea lice on farmed salmon. We simulated a 6-hour tidal exposure of adult non-gravid female ghost shrimp to concentrations of EB (as the insecticide Proclaim(R)) ranging from 0.01 to 100 ppb a.i. within artificial seawater alone or sediment + seawater. No treatment-related mortality was observed within the 96-hour test, but overt effects were observed, particularly at 100 ppb in both seawater (abnormal body position) and sediment (lethargy, inability to burrow). Results suggest that the 6-hour exposure was not sufficient to cause mortality. In a subsequent 96-hour test, we will expose the shrimp to EB mixed directly into the sediment simulated tidal cycle. As the shrimp re-establish their burrows, we anticipate increased exposure to the chemical and mortality. EB is more effective as a pesticide when ingested and, in comparison to IMI, targets the primary neurophysiology of crustaceans including sea lice and burrowing shrimp.

Small Ubiquitin-like Modifier, SUMO for short, is a protein involved in cellular regulation which can also be used as a biochemistry tool to express difficult-to-express proteins in the lab. I am investigating several SUMO proteases in order to learn more about the regulatory pathways it is involved in. We are focused on the traditionally used protease from Saccharomyces cerevisiae, a thermophilic version from Chaetomium thermophilium, as well as several redesigns of a homologous protein from the Saccharomyces SUMO protease to improve solubility by mutating solvent-exposed hydrophobic amino acids to polar amino acids using a computational protein design program called Rosetta. I am using thermal melting techniques to find melting points and gel comparison techniques to analyze the efficiency of each protease. Understanding of the kinetics and properties of these proteases and comparing them to each other will yield a greater understanding of how the system works, which versions are more efficient for in vitro use, and how the system can be manipulated in vivo.The goal of my research is to create a set of biochemical tools associated with SUMO proteins to be used in cancer research, as the SUMO system is known to be dysregulated in cancer. Understanding of the role SUMO plays in cancer will provide context for the development of a new generation of therapeutics, and understanding of the SUMO system as a whole will improve a current biochemical technique.

The forefront of modern medical research involves decoding the biological pathways that make disease transmission and perpetuation possible. Protein-based site-specific affinity reagents could allow us to antagonize harmful molecular interactions employed by pathogens, disrupt their toxic effects, and develop cutting-edge treatments. Consequently, the ability to express and purify rationally-designed proteins is the key to assessing their structure and function. To increase solubility and stability during recombinant expression, a genetic fusion to a small-ubiquitin-like-modifier (SUMO) is commonly used. The highly-specific SUMO protease is then used to cleave the SUMO fusion, leaving a completely intact and unmodified protein-of-interest. The current protease used originates from Saccharomyces cerevisiae. Known as Ulp1, the instability of this enzyme due to thermosensitivity and solvent-exposed hydrophobicity presents considerable limitations and can result in incomplete digestion of SUMO-tagged constructs. We present two approaches to mitigate these complications. First, we have discovered a homologous protease with a conserved catalytic site in the thermophilic eukaryote Chaetomium thermophilium. Second, using the Baker Lab’s pioneering computational design program, Rosetta, we have exchanged the hydrophobic surface residues of Ulp1 with hydrophilic side chains with the aim of improving stability in aqueous solution. We have characterized the kinetic function of these protease variants by monitoring digest efficacy through gel-based assays. Effectively, the improved proteases can equip the scientific community with a powerful new tool to facilitate protein-based drug design research.

Many infectious diseases are caused by bacteria growing in biofilms, a group of cells that stick together and adhere to surfaces, such as the human lung or implanted medical devices. Biofilms affect millions of people worldwide each year, often contributing to death. When a biofilm is successfully established, bacteria are up to 1,000-times more resistant to antimicrobial agents and extremely resistant to clearance by the immune system. These molecular fortifications make bacterial infections difficult to treat, with the possibility of relapse weeks or months after the use of antibiotics. Many infectious diseases caused by biofilm-forming bacteria disproportionately affect the elderly and immunocompromised, like Legionella and Bordetella, which cause pulmonary infections. My research focuses on preventing biofilm formation, and forcing bacteria that have already formed a biofilm to disperse. Molecular engineering was used to design a protein to activate LapG, a protein effector responsible for balancing whether the bacteria are free floating versus anchored. When LapG is active, bacteria shed their adhesive proteins anchoring them to surfaces, and become free floating. I am trying to develop a protein-based drug to fight biofilm-based infections by permanently switching LapG to the “on position.” Because this drug will be made of protein, there will be no toxic breakdown products, and the highly specific binding inherent to protein-based drugs will minimize the risk of side effects. Furthermore, protein-based drugs are genetically encodable, allowing us to genetically modify self-replicating probiotics, such as yogurt cultures or baker’s yeast, to produce this medicine. This will empower low cost drug manufacturing and distribution because local communities in developing countries can produce these therapeutics using readily available cooking equipment and ingredients, and administer them without fear of overdose or toxicity. The goal is to test the LapG binder in animal models of chronic infection, eventually moving to human clinical trials.