Obesity constitutes one of the greatest public health challenges, having a high prevalence and increasing the risk of serious complications. Obesity is essentially caused by an imbalance of energy intake and expenditure, which is under the tight regulation of the nervous system. The goal of this project is to investigate the genetic causes of abnormal food intake and eating regulation, by studying the different mechanosensory and chemosensory receptors present in the fruit fly Drosophila melanogaster’s digestive system. Tiffany will perform immunofluorescent staining and imaging using confocal fluorescence microscopy to identify the specific neurons that are involved in gut-brain communication. Following identification, Tiffany will analyze the spatial distribution of neural innervation and characterize the physiological and behavioral functions of specific neurons. The outcomes will further the understanding of neuron function and feeding regulation mechanisms.
Kaposi’s sarcoma-associated herpesvirus (KSHV) establishes lifelong infections and can cause various cancers in immunosuppressed individuals. KSHV lies dormant in infected individuals’ cells and reactivates intermittently to cause disease and promote transmission. Current scientific literature lacks an understanding of the KSHV gene open reading frame 69 (ORF69). In this project, Christian will employ a two-step mutagenesis technique in E. coli to generate ORF69 knockout and revertant mutants in a KSHV bacterial artificial chromosome (BAC). After transfecting a Kaposi’s sarcoma cell line with the BAC vectors, inducing lytic reactivation, and infecting 293T cells with supernatant from the induced cells, Christian will be able to determine if ORF69 is essential in the KSHV life cycle. The results have the potential to inform the development of novel drugs and immunotherapies for KSHV transmission and pathogenesis.
Human Cytomegalovirus (HCMV) infects 60-90% of humans globally, and while infections are largely asymptomatic, they can be severe or fatal in immunocompromised persons. No vaccines exist to prevent HCMV infection due to an incomplete understanding of the viral mechanisms used to evade host immunity and establish lifelong persistence. Complement is a system of proteins present in blood that serves as an initial line of defense against microorganisms; however, little is known about the role of complement in protection against HCMV. For this project, Hector will investigate the role of MASP1 (a complement activating protein) in HCMV immunity using a yeast-two-hybrid approach to screen for protein-protein interactions against an HCMV gene library. Identification of novel HCMV-complement interactions has the potential to inform the development of vaccines and novel drugs.
Natural killer (NK) cells play an important role in the innate immune system in eliminating viruses and tumors. Unfortunately in environments lacking class I major histocompatibility complex (MHC-I) proteins, as is the case in 40-90% of human tumors, the NK cells can become desensitized and unresponsive. In her project, Seungwon will modify the expression of two phosphatases, Ptpn6 and Ptpn 22, that have been found to be expressed at higher levels in anergic NK cells to study the molecular mechanisms of NK cell desensitization. Findings have the potential to guide NK cell cellular therapy.
Dengue disease is caused by four serotypes of dengue virus (DENV), and associated symptoms can range from undifferentiated fever to severe vascular leakage. DENV nonstructural protein 1 (NS1) was recently found by the Harris laboratory and others to be a key factor in causing the endothelial barrier dysfunction that leads to vascular leakage, but the mechanism is not yet completely understood. Richard will focus on identifying possible host factors critical for NS1-induced pathology by generating a list of host factors of interest from pilot gene expression analyses, and then validating their role in endothelial dysfunction using a murine dermal leak model. Richard will then assess the therapeutic potential of small molecule inhibitors of host factors critical for NS1-mediated pathology and create modified cell lines to better understand the overall mechanism.
Worldwide, we have more than 33 million people living with HIV (human immunodeficiency virus). It remains a challenge to find the best prevention methods. Keng’s research compares two new biomedical prevention methods that have used ART (antiretroviral therapy) to prevent HIV transmission in discordant couples (one member is infected but the other is not). One method is PrEP (pre-exposure prophylaxis), where the uninfected person takes antiretroviral drugs, and the other method begins ART in the infected member earlier than is clinically recommended to prevent transmission. The clinical trials data from both methods are published and available for analysis. Keng will use meta-analysis and cost-effectiveness analysis to compare and contrast both prevention strategies for a cohort of heterosexual couples living in southern Africa.
Stomatopods, also known as mantis shrimp, are some of the coolest marine crustaceans. They are powerful predators (for their size, at least) and are concentrated in tropical waters all over the world. The stomatopod rostrum, a segment of exoskeleton near the eyes, ranges from a simple triangular shape to something that looks more like a crown or the curved top of a palace. This summer, Irene will be looking into the evolutionary motivations of stomatopod rostrum variation. She plans to determine the function of the rostrum and the reasons for its wide variation by compiling environmental data, taking high-speed videos of stomatopod behaviors, and comparing rostrum shapes to their phylogeny.
Since the early 20th century, global surface temperatures have risen 1.4F, with the majority of the warming occurring in the past three decades due to anthropogenic activities. Significant changes in sea level, ecosystems, and ice cover are predicted to occur as a result of increasing temperatures. Katya aims to understand ecological responses to simulated and natural climate change in a subalpine meadow at the Rocky Mountain Biological Laboratory. She will maintain a database for the longest-running climate manipulation experiment in the world and gather additional information about the species abundance distribution and changes in albedo over the course of the summer. Larger implications of her project are greater insight into microclimate-ecosystem dynamics and the effects of warming on landscapes, which may be useful information for agricultural and water-management industries.
The rising economic and environmental cost of fossil fuels will greatly affect our reliance on them for global food transportation in the near future. Michal will design crop plans for plant-based food systems in Israel and Ireland — regions with radically different climates — to determine the feasibility of maintaining a locally grown, healthy plant-based diet. This summer, she will conduct research in Israel and Ireland, collecting technical evidence of soil and climate conditions to determine what can be grown in each area, gathering historical data on plant foods grown in the region, and interviewing nutritionists and permaculture experts to obtain information on local sufficient diets and sustainable crop-growing methods. She intends for this case-specific data to be a starting point for a crop plan designing method in resource-limited climates.
Tuberculosis (TB) is an infectious disease that often attacks the lungs and can be spread through the air by coughing, sneezing, and other airborne means. Approximately 2 billion people are infected with TB and around 1.6 million people die of this disease every year. Navpreet will develop a point of care (POC) diagnostic device that will be able to quantify specific TB biomarker levels in serum using electrical impedance spectroscopy. His project tests the hypothesis that the limit of detection can be improved by creating a 3D gel sensor as opposed to the standard 2D sensor for electrochemical detection. The versatile, low cost POC platform technology for TB diagnosis and other antibody-based assays will address the existing diagnostic needs of patients and clinicians in underserved regions.