Proteins perform a vast array of functions within all living organisms. These functions are heavily dependent on the protein’s 3-D structure. Cellular stress can result in the loss of protein structure and can lead to a wide variety of problems, one being the formation of insoluble protein aggregates. Aggregates can inhibit proper protein function, disrupt cellular homeostasis, and are implicated in many diseases. There exists a family of proteins, known as the Small Heat Shock Proteins (sHSPs), which are thought to combat aggregate formation. They interact with misfolded and aggregate-prone proteins (clients) to delay the formation of insoluble aggregates. How sHSPs delay aggregation is not well understood. I seek to characterize interactions between sHSPs and their clients. A binding interaction between the sHSP αB crystallin and the model client Δ131Δ (a mutant of staphylococcal nuclease) has previously been characterized by NMR. My goal is to confirm this interaction and look for additional interactions between these two proteins through chemical cross-linking. Chemical cross-linking is a process that links two proteins that interact. One can use this method to detect which surfaces of proteins are involved in a protein-protein interaction. The chemical cross-linker I am using is incorporated as an unnatural amino acid (p-benzoyl-L-phenylalanine, or BpA) into the sHSP αB crystallin. Upon exposure to UV light, BpA can covalently cross-link to another protein if it comes into close contact with it. This approach can allow us to explore how sHSPs interact with the client Δ131Δ. By gaining an understanding of this specific sHSP-client interaction, I hope to provide insight into general mechanisms of how sHSPs interact with clients, a process that plays a critical role in cellular health.

Cells and organisms must adapt to a variety of conditions to ensure survival. These adaptations have led to the evolution of a set of genetic stress response pathways, many of which have co-evolved to affect longevity. One of these pathways is the hypoxic response pathway, which is important for the response to diminished oxygen and is controlled primarily by the hypoxia inducible factor-1 (HIF-1). HIF-1 is a highly conserved transcription factor whose stabilization promotes increased lifespan and healthspan in C. elegans. Despite HIF-1 being highly conserved, similar stabilization of HIF-1 in humans leads to von Hippel-Lindau (VHL) syndrome, a disease characterized by increased tumor formation. Although the effects of global activation of the hypoxic response are well-documented, the tissue specificity and important downstream targets necessary for benefits or disease remain largely uncharacterized. My project focuses on the proteins downstream of HIF-1 that act to affect health and longevity. Work in our lab shows that multiple genes downstream of HIF-1 in C. elegans are sufficient to increase worm longevity when overexpressed in the absence of HIF-1 stabilization. One of these downstream genes that modulate worm aging is flavin-containing monooxygenase 2 (FMO-2). FMO-2 is a phase 1 xenobiotic metabolizing enzyme that may also play a role in protein homeostasis. We have found that the expression of FMO-2 either ubiquitously or in the intestine and head excretory glands of C. elegans increases lifespan and healthspan. My project involves further characterizing the FMO-2 protein by testing its role in resistance to stress and improving healthspan. In addition, I am contributing to epistasis experiments to determine whether FMO-2 acts in any other aging-related pathways. In characterizing FMO-2 in this way, my project seeks to better understand this protein in the context of health and longevity.

Poliovirus (PV) remains endemic in three countries and is responsible for sporadic outbreaks in several others. Clinical surveillance for acute flaccid paralysis (AFP) is the gold standard for PV surveillance. However, as few as 1 in 100 to 1 in 1000 PV infections will develop AFP, particularly in well-vaccinated populations. Environmental surveillance of wastewater using a bag-mediated filtration system is currently being investigated to detect sub-clinical circulation of poliovirus. However, the filter samples will be collected remotely and evaluated centrally, which requires a shipping period. During this shipping period, bacterial and fungal growth may degrade PV on the filter surface. Inhibition of fungal and bacterial growth is necessary to ensure PV survival on filters during transit from field collection to the processing lab. Shipping on icepacks at 4°C is costly, thus finding an alternative is ideal. Preservative agents were investigated as an alternative to reduce microbial growth while not affecting PV recovery from its performance methods. Preservatives investigated included sodium azide, calcium propionate, o-phenylphenol, and sodium benzoate. Preservative solution or PBS control was pumped into the positively charged Virocap filter and eluted with beef extract, pH 9.50. After 1.5 hours, the eluate was pumped out, pH adjusted, and dosed with 10^2 PFU/mL PV1. Filters were run in duplicate and samples were plated on BGMK cells for enumeration by plaque assay. 0.0195% sodium azide eluate had a 64% recovery when compared to PV expressed in the PBS control eluate. 0.1% calcium propionate had a 102% recovery, 2% sodium benzoate had a 101% recovery, and 0.02% o-phenylphenol had a 111.1% recovery. Sodium azide is not recommended as a good preservative for PV due to low recovery, but 0.1% calcium propionate, 2% sodium benzoate, and 0.02% o-phenylphenol should be investigated further for PV preservation and recovery in wastewater over time.

In many ways, our contemporary understanding of the Modern Civil Rights Movement, and its associated successes and failures, has been severely limited through socio-historical and political machinations to collapse and periodize it. Rather than situating it within or connecting it to the broader historical continuum and highlighting the rich multiplicity of forms of struggle and survival, the simplistic narratives we receive through media (and other forms of cultural production) are ones of heroes and villains—of near-infallible visionaries and separatist and corrupt radicals, one that highlights the contributions of the few at the expense of the many. Two such groups whose historical agency and significance suffer from such undertakings are the Black Panther and the Young Lords Parties. It can be said that both groups have suffered not from a crisis of denotation, but one of connotation—referring specifically to the ways in which their collective contributions have been socially diminished as they are instead associated with fear, needless violence, corruption, militancy and relegated to the margins. Thus my research asks: how did these groups function as powerful symbols of transformation during Modern Civil Rights Movement? To what end? How and why were individuals within these groups and even the organizations themselves framed as threats to the social order and how would their objectification exacerbate their struggles for equality? I seek to uncover through a careful examination of foundational documents, news articles and other print media, interviews, and film, how socially produced marginalization enabled a multiplicity of violence against them (and their associated communities) and also illuminate some of the associated contemporary consequences.

Humor is a universal part of every human life. Stoic philosophers like Plato emphasized self-control and believed that laughter diminishes self-control. Mark Twain said, “Humor is tragedy plus time.” The things that people find funny are deeply connected to what they regard as right and wrong. On the one hand, being ethical requires people to follow a set of moral principles that provides rules for their actions. On the other hand, humor often requires rule breaking and norm violation. Therefore the two concepts are often incompatible. Our experiment has shown the degree to which morals and humor correlate. Participants were randomly assigned to either the moral mindset or control condition. Participants in the moral mindset condition were instructed to write a story using a set of ethical words (e.g., honest, caring), whereas the control group was instructed to write a story using amoral words (e.g., banana, elephant). We then instructed participants to create a caption to a series of pictures that allowed us to assess their sense of humor. Finally the captions were rated by three trained research assistants for how humorous they were. Results suggest that participants in the moral condition produced less humorous captions compared to those in the control condition. We are currently extending the external validity of this finding by conducting this study in a business setting by soliciting responses to the survey from employees to rate fellow coworkers for their ethics and determining how humorous they are. Our research will have significant practical implications for hiring and human resource practices because a person that is humorous will have a better chance of being hired. Paradoxically, these employees are also likely to be less ethical and undermine organizational functioning in the long-term.

Aging research depends on the use of model organisms to test hypotheses about the biological mechanisms common to many organisms. One commonly used model organism is the roundworm Caenorhabditis elegans. Unlike homeothermic mammals, C. elegans are poikilotherms, and as a result of a variable internal temperature, they also exhibit variable longevity based on the ambient temperature. Under standard laboratory conditions, C. elegans are commonly grown in incubators ranging between 15°C and 25°C, and lifespan varies inversely with temperature; worms live longer at colder temperatures. Our recent data show that the relationship between temperature and aging has a genetic component. By measuring the lifespan of worm strains with mutations in genes found in established aging pathways, we have identified mutations that have opposing effects on lifespan at different temperatures. For example, utilizing lifespan assays I have conducted, we have found worm strains that live longer than controls at high or low temperature, but not both, as well as strains that are short-lived at specific temperatures. These experiments suggest there may be overlapping but distinct mechanisms driving aging at different temperatures, and we are developing hypotheses to explain the temperature-dependent mechanisms of aging. Thus far, our data are consistent with the hypothesis that genes that contribute to protein homeostasis promote longevity at higher temperatures, whereas genes that limit effects of toxic compounds (both internally and externally produced) promote longevity at low temperatures. Understanding the temperature-dependent mechanisms of aging in C. elegans will advance the aging research field by extending knowledge on a widely used model organism and by testing how the mechanisms of aging and disease may be conserved in homeotherms. We hope our results will suggest how and why many genetic longevity pathways are conserved from worms to mammals despite drastically different life histories.

With the increasing application of electromyography (EMG) sensor systems (method to measure electric potential generated during muscle contraction) in automation and robotics control, investigations on an effective user-interface are essential. My goal is to investigate solutions that enable valid communications between users and a system under complex sensor behaviors. If a user is unable to complete a motion or to continuously generate the proper control signal, the interface detects the desired signal and reproduces the intended result. There are two components in this research: (i) finding the behaviors of EMG signal, which determines the way users interact with the system, and (ii) adjusting or approximating the output to an ideal signal through visual feedback. To address the first task, I have processed the EMG sensor signal by implementing an analog and digital filter system to achieve a reliable EMG signal. Towards this, I created a LabView program to generate a signal of a desired function (e.g. Asin(ωt+φ)), by detecting the magnitude, frequency, and phase information of the input signal. Currently, my signal generation program works with a sinusoidal waveform in the presence of noise. However, physical EMG signals are not perfect sinusoidal waves. Using my program, the interface between the human-generated EMG signal and the computer generated result can be explored, with the goal of using EMG signals to control the computer generated signals. This will be accomplished by modifying the detection algorithm developed for the sinusoidal inputs.