UNC BIOLOGY DEPARTMENT
UNDERGRADUATE RESEARCH DESCRIPTIONS
Candidates for Honors and Research Commendations in Biology
Spring 2008
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Sam Abercrombie Research Advisor: Dr. Charles Mitchell Research Mentor: Dr. James Cronin
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Introduced species can affect community structures by decreasing species diversity and altering dominance patterns. One mechanism by which introduced plant species may change their communities is by altering herbivore and pathogen dynamics. Because non-native species allocate little energy to defensive traits, such as leaf toughness, and instead maximize their growth rates and nutrient absorption, they may be more palatable to generalist herbivores. Increased contact rates with herbivores enhances the risk of acquiring herbivore-vectored diseases, and simultaneously subjects exposed and damaged tissue to fungal infection. I measured leaf toughness as well as herbivore and pathogen damage on four grass species grown in monoculture at Mason Farm. I found that non-native grass species tend to have less tough leaves, and more herbivore and pathogen damage than native species. These results suggest that non-native plant species may cause indirect competition in their new communities by establishing new patterns of herbivore and pathogen interaction. |
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Isolation of Gene(s) Responsible for Binding of Agrobacterium tumefaciens to Plant Host Cells
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Brittany Baffer Research Advisor: Dr. Ann Matthysse
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Agrobacterium tumefaciens causes crown gall tumor formation in plants. Tumor formation results from transfer of DNA from the bacterium to host cells. The initial step in tumor formation involves attachment of bacteria to the plant. Without the ability to bind tightly, the frequency of transformation dramatically decreases. Previously isolated non-binding mutants of A. tumefaciens do not affect molecules directly involved in attachment. Thus, identification of molecules involved in binding has not been possible using bacterial mutants. The failure to isolate this class of mutants is thought to be a result of genetic redundancy. To identify genes whose mutant phenotype may be masked by genetic redundancy, I have cloned genes from A. tumefaciens into a non-binding strain of Escherichia coli and selected for clones containing DNA segments that enable E. coli to bind to alfalfa sprouts. |
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Developing a Novel in vivo Technique to Identify Unknown Substrates of the E3 Ligase Rsp5
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Rick Baker Research Advisor:
Dr. Brian Kuhlman
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The process of ubiquitination is observed in hundreds of cellular processes and is regulated by a cascade of protein classes, E1, E2, and E3. This cascade results in a substrate protein being labeled with ubiquitin, thus determining its cellular fate. E3 Ligases are responsible for substrate recognition and labeling with ubiquitin. The yeast E3, Rsp5, has been studied extensively, but many of its substrates remain unknown. With this is mind, the primary goal of my research is to use protein design to develop a novel in vivo technique to identify unknown substrates of Rsp5. This technique could hopefully be used in future research to identify unknown substrates of other E3 Ligases such as E6AP, a human E3 which plays a vital role in Angelman Syndrome. |
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Essraa Bayoumi Research Advisor: Dr.
Terry Combs |
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Insulin is a hormone with a vital role in glucose metabolism. Type-2
Diabetes, a disease which is characterized by a decreased response to
insulin, is often treated with Thiazolidinediones (TZDs). TZDs work by
binding to a receptor (PPARγ) in the nucleus of adipose tissue cells
which causes an increase of adiponectin, a hormone secreted exclusively
by fat cells. In conjunction with the increase of adiponectin, glucose
levels and insulin resistance are decreased. Presently, I am comparing
wild-type mice to mice that have a defect in the PPARγ gene to study the
role of PPARγ on the induction of adiponectin. Furthermore, I am looking
at two different strains of mice to determine whether genetic
differences play a role in the stimulation of adiponectin. Understanding
the mechanism by which adiponectin levels are regulated will give more
insight into the cause of Type-2 Diabetes and aid in the development of
more effective treatment.
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The Effect of Mitotic Spindle Tension on Histone Protein Turnover in Saccharomyces cerevisiae
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Lisa Bond Research Advisor: Dr. Elaine Yeh
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During cell division, duplicated chromosomes are anchored to either side of the dividing cell by structural units called microtubules. Histone proteins bind and coil these chromosomes into more compact structures. Those histone proteins bound to the chromosomal regions attached to microtubules (pericentric regions) are exposed to the tensile forces of microtubule contractions. This study used the budding yeast Saccharomyces cerevisiae to address the hypothesis that tension reduces the background rate of histone movement in a cell (turnover rate). The turnover rate of pericentric histones was compared to that of histone proteins bound to tension-free chromosomal arms. Furthermore, wild-type histone turnover was compared to turnover in tension-free cells. For these experiments, the microscopic method of fluorescence recovery after photobleaching (FRAP) was used to determine the turnover rate of a histone subunit tagged with green fluorescent protein. The results of this study illuminate the potential role of tension in cell death caused by histone malfunction. |
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Tactile Perception in Older Adults
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Alice Broadhead
Research Advisor: Dr. Mark Tommerdahl |
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Investigation of sensory perception in humans has been complicated by factors such limitations in spatial resolution of available brain imaging techniques. One way to bypass these difficulties is to have subjects report information regarding their perception of stimuli. I have taken this approach in studying the tactile perception in the elderly by means of a non-painful, non-invasive stimulator. The stimulator consists of two blunt probe tips attached to motors controlled by the use of computer software. The software then records quantitative data regarding subjects’ reported perception of vibrations and taps administered by the stimulator. Predictions from animal models as well as current understanding of human cortical processing will be used to interpret the data gathered. This research should contribute to a better understanding of cortical connectivity and plasticity in regions of the elderly brain pertinent to perception of tactile stimuli. |
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The Role of Palladin in Early Vertebrate Vasculogenesis
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Jessica Carter
Research Advisor: Dr. Carol Otey |
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The actin cytoskeleton is vital to cell physiology. Palladin is an actin-associated
protein with a critical role in cell morphology and motility. To explore
its role in embryonic development, a palladin-null mouse line was
previously developed. This mutant displayed multiple defects, including
failure of the neural tube to close anteriorly, a pronounced facial
cleft, and embryonic lethality by day E13. Still, the cause of
lethality is unknown. I hypothesize that palladin is necessary for
proper early embryonic vascular development in vertebrates. The
association of palladin with actin-based structures in many types of
cultured cells suggests that it may be required for the normal assembly
of cell-cell junctions in the heart and blood vessels. To test this, I
will perform whole-mount embryo staining of palladin-null mouse
embryos. In addition, I will knock down palladin expression in the
zebrafish D. rerio to determine if palladin’s role is conserved
in embryonic vasculogenesis.
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The Role of Nitric Oxide in Catechol-O-methyltransferase-dependent Pain Sensitivity
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Matt Conrad
Research Advisor: Dr. Andrea Neely |
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Temporomandibular joint disorder (TMD) is a common persistent pain
condition. Recently, our group demonstrated that TMD onset and
heightened pain sensitivity are associated with genetic variants of
catechol-O-methyltransferase (COMT) that exhibit low enzymatic activity.
Depressed COMT activity results in elevated levels of catecholamines,
which stimulate β2/β3-adrenergic receptors to
produce pro-inflammatory cytokines. These cytokines stimulate nitric
oxide synthases to produce nitric oxide. Nitric oxide likely drives
persistent pain conditions by inactivating the COMT enzyme and/or
causing oxidative stress reactions. Thus, the purpose of the present
study is to evaluate the role of nitric oxide in COMT-dependent pain
sensitivity. We will measure nitric oxide expression levels in rats
receiving a COMT inhibitor alone or together with nitric oxide synthase
inhibitors. We hypothesize that nitric oxide levels will be elevated in
animals displaying increased COMT-dependent pain sensitivity and that
blocking nitric oxide production will prevent the development of pain.
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Screen for Residues that Regulate Nucleotide Exchange in G Proteins
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Jeff Duffy
Research Advisors: Dr. Alan Jones & Dr. Henrik Dohlman |
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Responding to the extracellular environment is fundamentally critical to
all biological processes. G protein coupled receptors (GPCRs)
participate in this process by connecting extracellular cues to
intracellular downstream effectors. G proteins are one of the largest
and most ubiquitous groups of membrane bound receptors and respond to a
variety of signals including: drugs, light, odor, taste, hormones, and
neurotransmitters. G protein signaling is activated when the receptor
responds to a ligand and causes a conformational change in Gα allowing
GDP to be released and replaced by the higher concentration of GTP. The
plant Arabidopsis thaliana G protein is unique and releases
nucleotides spontaneously without receptor activation. In an effort to
discover how the Arabidopsis Gα protein maintains fast nucleotide
exchange without loss of stability I am employing a high throughput
screen for mutations in the Arabidopsis Gα gene that correspond
to residues that regulate nucleotide exchange in Gα proteins. |
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A Comparison of the Environmental Condition of Three Distinct Sites of Pokeberry Creek
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Katherine Evans
Research Advisor: Dr. Seth Reice |
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By
understanding the makeup of a biotic community within an environment
that is constantly changing in the face of human and natural impact, it
is possible to estimate the condition of the environment. Benthic
macroinvertebrates present in a stream are principle players in the
decomposition of dead organic matter by breaking the material down
through shredding and feeding activities. The rate of decomposition of
dead organic matter can reflect the amount of organisms present. After
identifying these organisms, the biodiversity can then be analyzed to
estimate the health of a stream. I am studying three unique sites of
Pokeberry Creek in Chatham County, NC. The biodiversity of the stream
is likely to have been affected by nearby construction and a severe
drought. By determining rates of leaf decomposition, I can estimate and
compare the condition of the sites and make assessments about the
impacts of construction and drought.
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The Role of SOX9 in Cell Lineage Specification in the Mouse Small Intestine Epithelium
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Eric Formeister
Research Advisor: Dr. Scott T. Magness |
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The small intestine epithelium (SIE) has one of the fastest regeneration
and growth rates of any tissue. Though this suggests the existence of
an intestinal stem cell (ISC), this cell has not yet been defined
because of the lack of a specific ISC biomarker. The Magness Laboratory
has implicated the transcription factor SOX9 as a potential ISC
biomarker. We have demonstrated differential levels (high and low) and
restricted expression of SOX9 in the putative location of the ISC. High
SOX9 expression identifies differentiated enteroendocrine cells in the
SIE whereas low SOX9 expression marks proliferative stem/progenitor
cells. These data suggest that a threshold level of SOX9 is important
in committing a stem/progenitor cell to an endocrine fate. To test this
hypothesis, I aim to over-express SOX9 in an ISC line and hope to
fate-specify cells to an enteroendocrine lineage. This research will
provide further insight into the control of SIE proliferation,
maintenance and repair in normal, diseased and cancerous states.
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Richard Frye
Research Advisor: Dr. David Threadgill |
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The Epidermal Growth Factor Receptor (EGFR), responsible for growth and
proliferation, has been implicated in colorectal cancer. Drugs that
target EGFR have been developed and, while exhibiting promising
preclinical results, have been ineffective in large-scale clinical
trials. Previous data have shown that colorectal tumors still develop
in conditional EGFR knockout models. This suggests that these tumors
exploit a pathway independent of EGFR activity. If these EGFR-independent
tumors are present in wild-type tumor populations (represented by the
Adenomatous Polyposis Coli Multiple Intestinal Neoplasia (APCmin)
model), characterization of the EGFR-independent pathway could provide
new therapeutic targets. Determining whether this subset exists in
wild-type tumor populations is a first step toward developing more
effective therapeutic strategies. To investigate the genetic and
molecular differences between EGFR-independent and APCmin
tumor populations, genetic targets were assayed using quantitative
PCR to investigate ligand distribution and molecular targets were
assayed using immunohistochemistry to investigate apoptotic activity.
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Presentation of Smith Antigen to B Cells by Dendritic Cells and Macrophages in Mus musculus
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Chris Hilliard
Research Advisor: Dr. Barbara Vilen |
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The autoimmune disease systemic lupus erythematosus is characterized by
the unregulated secretion of autoantibodies by immune cells. Prior
research indicates that chronic exposure to antigen, we believe Smith (Sm)
antigen, is required to suppress this secretion. My research focuses on
identifying the particular receptor on dendritic cells (DCs) or
macrophages that is responsible for presenting Sm. I apply a fluorescent
antibody specific for Sm to DCs derived from the bone marrow of mice
with various receptor genes knocked out and then examine the DCs with
confocal light microscopy. In doing so, I can determine if the receptor
in the knock-out mouse is the receptor that binds to and presents Sm.
The results of this research will help to describe the molecular basis
for secretion dysregulation of immune cells in individuals with lupus..
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Expression of the Xenopus Transcription Factor Tbx20 in Early Neurogenesis
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Elizabeth Jarvis
Research Advisor: Dr. Frank Conlon |
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Vertebrate development involves a complex series of events that are
highly regulated at the molecular and cellular levels, and determining
the signal transduction pathways that regulate gene expression is
essential to understanding proper development. Tbx20, a member
of the T-box transcription factor family, is expressed throughout
development in several tissues and cell types where it functions as a
regulator of embryonic patterning and organogenesis. Since Tbx20
is necessary for nervous system development, it is important to
understand how Tbx20 expression is controlled in neuronal cells.
My project investigates the regulation of Tbx20 expression in
Xenopus, the African clawed frog. Using a transgenic approach, I
have identified two DNA sequence elements that are sufficient to drive
Tbx20 expression in the developing nervous system. My goal is to
reveal the molecular pathways of Tbx20 expression in neural
development, thereby gaining a better understanding of the role of
Tbx20 in mechanisms of human development and disease.
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Characterization of Sox4 as an Intestinal Stem Cell Marker
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David Lorance
Research Advisor: Dr. Scott Magness |
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Stem cells have been identified in many tissues, including the brain,
bone marrow, liver and skin; however, stem cells have not been
identified or defined in the intestine due to the lack of specific cell
markers. Yet, the intestinal epithelium is a remarkably proliferative
tissue, engaging in entire cell turnover every 3-5 days. This suggests
the existence of a stem cell pool in the intestine. Recently,
stem/progenitor cells in the retina have been marked by the SRY-related
HMG-box (SOX) family of transcription factors. Further,
preliminary experiments have localized expression of one of these
transcription factors, Sox4, to a putative stem cell niche in the
intestine. Thus, the protein Sox4 may mark stem/progenitor cell
populations in the intestine. To test this, a dual Sox4 cyan fluorescent
protein (CFP) reporter and Cre recombinase lineage marking
transgenic mouse is being generated. This “knock-in” mouse model stands
to identify and define Sox4-expressing cells.
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Conditions Affecting α-Synuclein Aggregation and its Implications in Parkinson’s Disease
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Evan Lutz
Research Advisor: Dr. Gary Pielak |
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Affecting over a million people in the United States, Parkinson’s
disease is a degenerative disorder that impairs motor skills and
speech. Parkinson’s disease is characterized by the presence of Lewy
bodies, which contain large amounts of the protein
α-synuclein,
in dopamine producing neurons of the midbrain. Much of this sequestered
protein is in fibrils, a non-covalent aggregate of monomer α-synuclein.
I am currently studying the ability of mechanical agitation to cause
fibril degradation as well as the ability of oxidizing agents to
stabilize aggregates by forming covalent cross-links at exposed tyrosine
residues. My research aims to determine intracellular conditions that
could affect the progression and stability of α-synuclein
and will potentially shed light on the structure and conformation of
α-synuclein during its aggregation
pathway. These results could potentially lead to a better understanding
of the change in intracellular conditions during the progression of
Parkinson's disease.
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Gene Order Polymorphisms in Yeast
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Biff Mann
Research Advisor: Dr. Jason Lieb |
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DNA polymorphisms across populations are well-documented, as are the
molecular events of point mutations and changes in gene copy number.
However, the transposition of genes from one chromosomal location to
another is poorly understood. The scope of this project is to analyze
gene expression patterns across transposed regions of the yeast genome.
We combined two microarray-based techniques to develop a high-throughput
method of identifying and locating transpositions in yeast. The
experiments were performed on genomic DNA resulting from a cross between
two strains of yeast: one very similar to the sequenced strain, the
other known to have many transpositions in its genome. Additionally, I
am conducting other experiments on gene expression in the nematode C.
elegans.
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Doug Meardon
Research Advisor: Dr. Mark Peifer |
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During embryonic development, morphological changes like organ
development require strong cell-to-cell adhesion. For mechanical
strength, cells adhere at cellular junctions connected to the
cytoskeleton; one such type is the adherens junction (AJ). Recently,
the Echnoid-Canoe protein complex has been proposed as a secondary
system of adhesion at AJs. Canoe is the intercellular protein, which is
proposed to interact with actin, a cytoskeletal molecule. Using seven
mutant alleles of canoe, I am looking at Canoe’s role in
embryonic development in Drosophila melanogaster (fruit fly).
After I have characterized the morphological defects of the alleles, I
want to determine the molecular basis of the phenotypic differences
between the alleles through sequencing and western blots. While Canoe
has been shown to be important during development in Drosophila,
the human homolog of Canoe, Afadin (Af-6), has been implicated in acute
leukemia. By relating its structure to its function, I hope to further
elucidate Canoe’s role during development.
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The Role of Bub1 Loss in Transformation
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Jordan Morreall
Research Advisor: Dr. Terry Van Dyke |
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One of the most common developments during tumorigenesis is aneuploidy.
Aneuploidy is abnormal chromosome number, which can arise from the
failure of the spindle checkpoint. The spindle checkpoint arrests
mitosis at metaphase if the chromosomes are not aligned properly at the
metaphase plate. One gene involved in activating the spindle checkpoint
is Bub1, of which an inducible mutation has been generated. Using this
mutation, this work investigates the degree to which Bub1 loss affects
the rate of oncogenic transformation in vitro. Transformation
assays were conducted on wild-type, Bub1-heterozygous, and
Bub1-homozygous mouse embryonic fibroblast (MEF) cultures. These assays
used lipid transfection systems, and continue now with retroviral
transfection. The conclusive results of these assays will improve the
understanding of Bub1’s significance in tumorigenesis. More broadly,
the results will show how such oncogenes can promote uncontrolled
growth, and depending on the number of functional alleles at work,
possibly inhibit growth as well.
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Bimal Patel
Research Advisor: Dr. Todd Vision |
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An
important descriptor of natural genetic variation is the extent of
nonrandom association between alleles in a population, or Linkage
Disequilibrium (LD). The extent of LD is governed by the rate at which
recombination breaks up such associations, which can in turn be affected
by a number of factors, including the mating system and the presence of
segregation distortion. In this study, I am measuring the extent of LD
in two closely related species of monkeyflower: the outcrossing
Mimulus guttatus and the selfing M. nasutus. I am testing
whether LD extends over longer distances in the selfing species, and
whether LD is elevated in the region of a locus that is known to undergo
strong segregation distortion in crosses between the two species.
Understanding the level of LD and the factors that influence it will
facilitate the genetic mapping of complex traits in these species.
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Gabriel Pollock
Research Advisor: Dr. Edward Perl |
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The perception of pain is mediated by sensory neurons known as
nociceptors and is normally a reaction to tissue injury. However, cases
of highly exaggerated levels of pain exist in a phenomenon known as
hyperalgesia. Pain is regulated by the type and concentration of
molecular receptors that are expressed in sensory neurons. Change in the
expression of these molecular receptors is an established means of
controlling the reactivity of cells, and it is hypothesized that such a
change is connected to this pathological pain. It has been shown that
both local and systemic application of Nerve Growth Factor (NGF) is
sufficient to induce cases of hyperalgesia. The goal of this research is
to show the effects that NGF has on the reactivity of sensory neurons to
neurotransmitters through electrophysiological testing. By better
classifying the mechanism by which hyperalgesia is induced, this project
will provide insight into how the body regulates pain..
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Characterization of a Novel Putative Methyltransferase that is Enriched on the Inactive X-Chromosome
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Sonya Purushothaman
Research Advisor: Dr. Terry Magnuson |
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X-chromosome inactivation (XCI) is the transcriptional silencing of most
of the genes on one of the two X-chromosomes in cells of female mammals,
and is necessary to achieve dosage compensation of X-linked genes
between males and females. The study of this phenomenon provides unique
insight into epigenetics—reversible chromatin modifications which are
stably inherited through cell division. Upon immunoflourescence
staining of trophectoderm stem cells (TS), we discovered that an
antibody (1822) raised against the Cdx2 protein (a transcription factor)
detects the inactive-X, despite the fact that Cdx2 has not been
implicated in XCI. Based on genetic, molecular, and bioinformatic
analyses, we hypothesize that the 1822 antibody is detecting a novel
protein that possesses methyltransferase activity, and is necessary for
proper XCI. By discovering this protein and its relation to XCI, we
hope to better understand the epigenetic mechanisms that control gene
expression and cellular transcriptional memory.
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Anti-tumor Activity of MerTK-deficient Mice
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Will Rearick
Research Advisor: Dr. Rebecca Cook |
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Receptor tyrosine kinases are cell membrane receptors that regulate many
cellular processes and have been implicated in a variety of cancers. One
such kinase, MerTK, is widely expressed in mice and humans, but its
function in many tissues remains unclear. We have observed that MerTK-knockout
mice are resistant to the formation of several tumor types. I am
investigating this immune-mediated anti-tumor response, specifically in
lympocytes known to express MerTK. I will be inoculating wild-type and
MerTK-deficient mice with tumor cells and comparing the quantity of
macrophages, dendritic cells, and cytotoxic T-lymphocytes at the
injection sites. I am also quantifying various markers to characterize
the type of response by each cell type, hoping to identify the cell type
or types responsible for the tumor resistant phenotype. A better
understanding of this mechanism may allow MerTK inhibition to become a
viable strategy for treatment of cancer patients.
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Induction of Cellulose Synthesis by Agrobacterium tumefaciens
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Emily Roberts
Research Advisor: Dr. Ann Matthysse |
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Agrobacterium tumefaciens
induces crown gall disease in dicotyledonous plants by transferring a
segment of DNA from the tumor-inducing (Ti) plasmid to the plant. Key
elements of this pathogen-host interaction include A. tumefaciens’
attachment to a plant and the induction of virulence (vir)
genes located on the Ti plasmid. Binding becomes permanent once the
bacteria initiate cellulose synthesis, which is known to be induced by
malate, pectin or soytone. The vir genes are induced by
plant-released phenolic compounds and their expression is increased by
sugars such as arabinose. The A. tumefaciens gene Atu3104
encodes an α-L arabinofuranosidase, which may release arabinose from the
plant cell wall. Immediately downstream, Atu3103 encodes an ABC
transporter homologous to an E. coli arabinose transporter. Using
genetic and molecular approaches, we are characterizing the role(s) of
these genes in the overall signaling pathway that leads to the
production of cellulose, resulting in permanent binding and virulence.
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The Use of Four Elephant Corridors by Wild and Domestic Animals in Mudumalai Wildlife Sanctuary
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Nitin Sekar
Research Advisors: Dr. Raman Sukumar, Dr. R. Haven Wiley, Dr. Jack Weiss, &
Dr. Peter White |
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Large animals, such as the Asian elephant, typically require large,
uninterrupted areas to provide for their basic needs. Due to habitat
destruction by humans in the last centuries, much of the Asian
elephant’s habitat has been cut up into fragments too small for viable
populations of elephants. As a result, conservationists have begun
reconnecting these patches with “wildlife corridors,” thin strips of
habitat that allow animals to move between habitat patches without
encountering human settlements, giving them the access to resources they
need to survive. Near Masinagudi village in Mudumalai Wildlife
Sanctuary, India, there are four such corridors. However, local farmers
are allowed to graze their animals and collect firewood in the
corridors. Using line-transect dung counts and signs of firewood
collection, my research examines which animals are using the corridors
and whether greater use of the corridors by humans and domestic animals
correlates with reduced use by wild animals.
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Caitlin Shaw
Research Advisor: Dr. Steven Young |
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Endogenous cannabinoids (endocannabinoids) are unsaturated fatty acids
which can activate the same G-protein linked receptors that bind the
psychoactive components of marijuana. Previous animal studies have
demonstrated the important role of endocannabinoids in embryo
implantation. Two major endocannabinoids are present in mouse
endometrium, and the expression of the enzymes responsible for their
synthesis and degradation is highly regulated by the mouse estrous
cycle. However, very little is known about the regulation or role of
endocannabinoids in human endometrium. Preliminary research has
identified all the major endocannabinoid anabolizing and metabolizing
enzymes in the human endometrium. Using Real-Time PCR and
immunohistochemistry staining methods of human endometrial tissue, I
will examine menstrual cycle-dependent changes in expression of the
enzymes required for the synthesis and breakdown of endocannabinoids.
This study will hopefully lead to a better understanding of possible
causes of infertility in women.
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Prothoracicotropic Hormone: A Role in the Adult Insect
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Chelsea Snyder
Research Advisor: Dr. Lawrence Gilbert |
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The development of insects is controlled by a unique endocrine system.
The tobacco hornworm, Manduca sexta, has provided much insight on
the functioning of this novel system. In this insect, prothoracicotropic
hormone (PTTH), a brain hormone, stimulates the prothoracic glands to
secrete ecdysone. Ecdysone, the “molting hormone”, controls insect
metamorphosis through a series of molts until maturity. In the mid-pupal
stage, the prothoracic glands undergo programmed cell death because
ecdysone is not needed for molting in adulthood. However, a pilot study
suggested that PTTH is found in the brains of adult and near-adult
Manduca sexta. The question then is: does PTTH have a new, undefined
role in the adult insect, or is it merely leftover from earlier stages?
In vitro experiments exploring this question have shown that PTTH
present during adult life is functional in stimulating larval
prothoracic glands to secrete ecdysone and that PTTH may have a role in
insect reproduction by changing protein synthesis and activity.
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Cell Cycle-Controlled Degradation of E2F1 in Drosophila Imaginal Discs
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William Jackson Turbyfill III
Research Advisor: Dr. Bob Duronio |
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Progression of the cell cycle is controlled and regulated through the
interaction of a collection of proteins. E2F1 is a transcription factor
that induces expression of genes involved in DNA synthesis. Previous
studies have shown that E2F1 is destroyed during S-Phase in Drosophila,
and we hypothesize that this is an important mechanism for regulating
E2F1 activity during the cell cycle. Our preliminary data suggests that
this S-phase-specific destruction of E2F1 is mediated by a Cullin
4-based E3 ubiquitin ligase complex. This observation was made with
cultured cells, and I am testing whether the Cul4 E3 ligase is
responsible for E2F1 destruction in vivo. I will analyze mutant
clones of Cul4 and its adaptor DDB1 in Drosophila as well as an E2F1
mutant that contains a mutation that prevents binding to the Cul4 ligase.
These experiments should expound upon the mechanism of E2F1 destruction
and whether this is important for cell cycle progression in vivo.
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Genetic Cloning of aik1aik2 Suppressors
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Michael Westafer
Research Advisor: Dr. Joseph Kieber |
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Directional expansion is responsible for the development and,
ultimately, the morphology of individual plant organs. In normal roots,
cells divide at the apical root meristem and elongate before
differentiating, causing the long shape of the root. Elongation of
cells has been linked to the pattern of cellulose microfibrils, which
are wrapped in a spiral around the cell, preventing lateral expansion.
Two genes, AIK1 and AIK2, have been previously identified which, when
both mutated, disrupt anisotropic cell elongation of roots in
Arabidopsis thaliana, resulting in swollen roots as the individual
cells expand radially. Point mutations in two genes suppress the
aik1aik2 swollen phenotype, thereby restoring anisotropic growth.
The goal of my research is to clone these suppressor genes. Discovering
genes involved in regulating this morphology will aid in further
understanding of anisotropic growth in the AIK regulated pathway as well
as plant morphology in general.
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Analysis of TGF-β1 Receptors as Potential Genetic Modifiers of Cystic Fibrosis Lung Disease
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Kiri Wiggins
Research Advisor: Dr. Michael Knowles |
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Cystic fibrosis (CF) is a recessive genetic disorder, most often caused
by the ΔF508 mutation in the cystic fibrosis transmembrane conductance
regulator (CFTR) gene, which results in a single amino acid
deletion. Patients homozygous for this mutation display great
phenotypic variation in CF lung disease severity. Our goal is to study
potential genetic modifiers of CF, or genes that do not cause CF but may
influence disease phenotypes. TGFβ1, the gene encoding the
protein transforming growth factor β1 (TGF-β1), is a genetic
modifier of CF lung disease. My project, therefore, focuses on two
receptors for TGF-β1 to determine whether an association exists between
genotypes at single nucleotide polymorphisms (SNPs) within these genes
and the severity of CF lung disease.
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