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Biochemistry - Huntsman Cancer Institute
My name is Marlon. I like to play piano, participate in sports, spend time with my pets, and am an avid supporter of the Utah Jazz.
Therapeutic Efficacy: Exploring Drug Testing Strategies for Targeting Short form RON
A class of enzymes called tyrosine kinases are proteins that control many cellular functions and have roles in cancer promotion. Among the proteins implicated in promoting aggressiveness in breast cancer, short-form RON (sfRON) is a tyrosine kinase that promotes growth and metastasis when overexpressed in breast cancer cells and is associated with poor survival in patients. Developing strategies to inhibit the function of sfRON is crucial for better treatment of breast cancer. To inhibit sfRON signaling in breast cancer, we evaluated treatments named PROTACS (Proteolysis-Targeting Chimeras) that link enzymes to the protein of interest to ubiquitinated and degrade the targeted protein. To test this hypothesis, we used the breast cancer cell line T47D with overexpression of sfRON to test two different treatments with variable doses.
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Dr. Sophie Caron's Lab
My primary interests lie in biology and anthropology. I am especially drawn to the field of neurobiology. To deepen my understanding in these areas, I have been working in a neuroscience research lab that studies fruit flies. In addition, I assist teaching the course BIOL1625 under Dr. Adam Rupper. I aspire to further my education in medical school through an MD/PhD program, where I could apply my knowledge of research and medicine and work to become a Hematologist/Oncologist.
Investigating the function of Drosophila melanogaster Arc genes in sleep
The mammalian activity-regulated cytoskeleton-associated protein (ARC) gene is expressed in neurons and is known to regulate different neuronal processes such as memory formation and sleep homeostasis. In Drosophila melanogaster, the functions of the homologs dArc1 and dArc2 – which are also expressed in neurons of the fly brain – remains largely unknown. We have shown that dArc1 and dArc2 are expressed in neurons of the brain, and that dArc1 is expressed in a subset of serotonin neurons. To begin investigating the role of dArc genes in flies, our lab generated novel dArc mutants in which either dArc1, dArc2 or both dArc genes were deleted henceforth referred to as the dArc1-/-, dArc2-/- or dArc1/2-/- mutants. We used the Drosophila Activity Monitoring System, which are individual sleep assay chambers that use an infrared light to measure sleep activity in flies. Our results show that dArc mutant flies show a robust increase in daily sleep compared to wild type flies. I hypothesize that dArc1 and dArc2 expression specifically in neurons is necessary for behavioral rescue of sleep phenotype. We used the Gal4-UAS system to investigate the sufficient cell type for Arc to regulate sleep. Our data shows that expression of the dArc genes in all cell types, all neurons, or specifically, serotonin neurons cannot restore sleep to wildtype levels. These results suggest that dArc1/2 regulation of sleep is under stringent control and might not be rescued by simply expressing dArc1 and dArc2 ectopically at unusually high levels. We are currently testing this idea by generating genomic rescue constructs that should recapitulate more faithfully the endogenous expression of patterns of dArc1 and dArc2. Altogether, this study will delineate the cellular mechanisms that enable dArc genes to regulate sleep.
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School of Biological Sciences
My name is Megan DuVal, and I’m majoring in Biology with an emphasis in Ecology, Evolution and Environment and minoring in Mathematics at the University of Utah. I work in Dr. Jack Longino’s lab and Dr. Rodolfo Probst’s SRI stream, where I use genomics, cutting-edge Nanopore sequencing, and morphology to study the evolution of the army ant genus Labidus. I became involved with army ant research my freshman year, when I worked on a project studying the flight seasonality of army ant males, and I’ve been fascinated by army ant biology and evolution ever since. After graduating from the U, I plan to pursue a PhD in ant systematics and evolution and become a professor, allowing me to continue investigating insect evolution. When not studying ants, I enjoy hiking, baking, reading sci-fi, and playing piano.
Conserving a keystone predator in the Americas: integrating phylogenomics, biogeography, and species-level taxonomy for a widespread army ant genus
Army ants (Formicidae: Dorylinae) are top predators throughout most tropical and subtropical regions of the world. Their nomadic colonies and cooperative social hunting make them behaviorally and ecologically unique keystone species of conservation concern vulnerable in areas affected by habitat fragmentation. Conservation efforts are hampered by outdated species-level taxonomy, which hasn’t been updated since the 1950s for many genera. For Labidus, a widespread, ecologically important army ant genus in the Americas, there are currently seven valid species recognized solely based on morphology of workers and/or males. Three species are only based on males, which need to be associated with workers, and within the four primarily worker-based species, there are likely cryptic species. To address these issues, we applied cutting-edge phylogenetics and phylogenomics to update the species-level taxonomy. To construct our phylogenetic tree, we used ultraconserved elements (UCEs, which use thousands of regions across the genome and can accurately infer evolutionary relationships across broad timescales) from 21 specimens, 66 COI barcodes from the Barcode of Life Database (BOLD), and 78 new COI barcodes obtained through in-house Nanopore sequencing. We found that Labidus contains at least 13 species and that all of the previously recognized wide-ranging species are made up of multiple cryptic species with more restricted ranges. We were able to associate all three previously identified male-based species with their respective workers. We have also found patterns of parallel and sympatric biogeography across multiple Labidus clades. Our UCE+Nanopore approach allows for an updated taxonomy of Labidus, leading to a better understanding of its evolutionary history and a better ability to promote its conservation.
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Department of Chemistry
Can short-term knee extensor training improve locomotor muscle microvascular function and exercise tolerance in patients with heart failure with preserved ejection fraction?
Patients with heart failure with preserved ejection fraction (HFpEF) exhibit locomotor muscle microvascular dysfunction. Many pharmacological interventions have failed in improving microvascular function in patients with HFpEF, however, there is evidence that exercise training may be more effective in this population. Knee extensor exercise training is an intervention that our group has demonstrated has improved vascular function in healthy adults. Given this, we tested the hypothesis that a knee extensor exercise training intervention would improve locomotor muscle microvascular function in patients with HFpEF.
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College of Science, Science Research Initiative
I am a second year undergraduate student studying biology with an emphasis in neurobiology. I have an honors integrated minor in Health, as well as plan to minor in chemistry and psychology. I began this research in Rodolfo Probst’s SRI stream, and have continued as an LA in his stream.
Unveiling Cryptic Avifauna Diversity Using DNA Barcoding: A Case Study In the Passerine Genus Emberiza
Biodiversity loss poses a significant threat, requiring accurate species assessment and conservation strategies. Non-invasive and cost-effective techniques should be prioritized, especially when dealing with threatened vertebrate fauna. By focusing on cryptic avian species in the genus Emberiza (Passeriformes: Emberizidae), we designed an affordable molecular pipeline integrating DNA barcoding with Nanopore sequencing to address species boundaries and provide conservation information. We conducted non-invasive DNA extractions from individual feathers of 242 specimens collected in the Aras River Riparian Corridor (ARRC), an important ecological hotspot in Turkey. By targeting the cytochrome oxidase subunit I (CO1) region, our goal was to differentiate boundaries in Emberiza taxa with subtle morphological differences (E. schoeniclus schoeniclus and E. schoeniclus caspia). We aimed to identify potential cryptic lineages while using cutting-edge next-generation sequencing (NGS) of multiplexed specimens with nanopore sequencing. We obtained 222 Emberiza DNA barcodes. Clustering analysis recovered a paraphyletic assemblage and a clade, the latter recovering the majority of the barcodes, separated by at least 8% genetic difference. In both cases, we observed a mixture of barcodes from both subspecies, suggesting that morphological characteristics are not reflected by genetic separation. Our phylogenetic results also suggest the existence of putative cryptic Emberiza species, highlighting the importance of the ARRC for conserving avian diversity. We demonstrate that our pipeline can be used for conservation initiatives while expanding our knowledge of avian diversity. Moreover, we highlight the potential of NGS DNA barcodes as a powerful tool for aiding conservation efforts amidst biodiversity loss.
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A Glance into the Origin of Life through the Lens of the DNA Repair Enzyme MutY from the Lost City Metagenomes
I have been studying the DNA repair enzyme MutY found at the Lost City thermal field 3000 feet deep in the Atlantic Ocean with conditions similar to those that may have shaped the origin of life. With no sunlight and very little oxygen, life at the Lost City is driven by chemical transformations in rocks at extremely high levels of pH and temperature. DNA in all organisms strictly follows base pairing rules in which A pairs with T and G pairs with C. We all think of oxygen as beneficial, but it can cause damage to DNA. Oxidized guanine (OG) violates the base pairing rules and pairs with A. This causes mutations, which can lead to changes in the genetic information. The mutagenic potential of OG was a challenge that had to be solved early in the emergence of DNA-encoded life. The enzyme MutY functions in suppressing mutations and therefore protects us from developing cancer by finding and removing A from OG:A mispairs. In my effort to replicate conditions at the Lost City so as to explore how the DNA repair enzyme MutY evolved to function in this strange environment I need to purify the enzyme. I used DNA cloning to attach the MutY-encoding genes to a soluble bacterial protein called GST that hopefully will make it easier to purify the MutY proteins. Encouragingly, these fusion proteins expressed well in bacteria and appeared to be soluble. I am now exploring different conditions looking for optimal enzyme activity, which I predict to be different from what familiar bacteria can tolerate. Basic science research on how DNA repair enzymes adapted to the strange environment at the Lost City may inform future translational applications to treat and cure cancer and thus ensure a healthy society in Utah.
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Department of Chemistry
Hi! I am a 4th year biochemistry student interested in teaching. I have been a TA for organic chemistry courses for 2 years and am now also a TA for a biochemistry lab, and I love it! My poster project was not done in a research lab, but was a project completed by me, Ella Bleak, and Samantha Johnson in my quantitative analysis lab course.
Melatonin is a naturally produced hormone regulating the sleep-wake cycle. Supplements for melatonin are commonly used to aid people with trouble sleeping but are not FDA regulated. Studies have shown that there is a large difference between the dosage on packaging and the concentration of melatonin in individual tablets. The purpose of our experiment was to investigate if time-release capsules release a gradual dosage or if the capsules release their dosages more quickly than company claims.
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Synthesis and characterization of pyridyl aza crown ethers able to chelate rare earth elements