Tag: Biology

Regulation of the Kynurenine Pathway in Neurospora crassa

Presenter: Haley Speed – Biology

Faculty Mentor(s): Eric Selker

Session: (In-Person) Poster Presentation

The kynurenine pathway is a metabolic pathway that degrades tryptophan into NAD+ and several other essential biomolecules. In humans, the kynurenine pathway is closely tied to healthy and disease states, and current research indicates that altering the activity of the pathway could have therapeutic benefits. This ancient pathway is also conserved across all eukaryotes. Previous work from the Selker lab using the filamentous fungus Neurospora crassa as a model organism suggested that the regulation of this pathway is intertwined with general chromatin control processes, including H3K36me and chromatin remodelers. My research aimed to identify novel regulatory factors affecting this pathway. I used a phenotypic screen of the Neurospora Functional Genomics Project strains. In addition, RT-qPCR analyses of RNA for kynurenine pathway enzymes helped reveal which strains were abnormally inducing the pathway. In total, five genes of interest have been identified as potential regulators of the kynurenine pathway, including one factor also tied to MAPK pathway induction. Further research is needed to characterize these genes to understand how they may function to regulate the kynurenine pathway, or if their regulatory function is tied to chromatin control.

An investigation of novel left-right patterning genes in zebrafish

Presenter: Maisey Schering – Biochemistry, Biology

Faculty Mentor(s): Katie Fisher, Daniel Grimes

Session: (In-Person) Poster Presentation

Breaking of left-right (L-R) symmetry is a fundamental part of animal development. To facilitate this, cell to cell communication via extracellular fluid flow plays a critical role. Failure of this communication results in developmental diseases such as congenital heart disease and abnormal L-R positioning of the organs, termed heterotaxia. Understanding the mechanisms by which fluid flow signals control asymmetry is essential for understanding how to treat these diseases. In embryonic development of zebrafish, the model organism of this project, asymmetric flow in Kupffer’s vesicle (KV) breaks L-R symmetry. The flow signal results in asymmetric repression of an mRNA, dand5, triggering asymmetrical development of the emerging organs. How cells sense and transduce fluid flow, leading to dand5 repression, is not understood. My mentor in the Grimes lab, Katie Fisher, performed a literature review that resulted in 90 novel candidate genes which might regulate L-R asymmetry. These genes are all expressed at the right time and place during development to control fluid flow signaling. We are using a CRISPR/Cas9 screen to identify which of these genes are essential for L-R patterning. Several genes of interest have been identified and homozygous lines with these mutations are currently being generated. I will describe our ongoing screening efforts and early results. By completion of this project, we will know how these novel genes act to ultimately control organ asymmetry.

Measuring soil respiration in response to enhanced silicate weathering and mycorrhizal associations

Presenter: Emily Scherer – Biology

Faculty Mentor(s): Hilary Rose Dawson, Lucas Silva

Session: (In-Person) Poster Presentation

Enhanced silicate weathering (ESW) is emerging as a top contender to reduce atmospheric carbon and mitigate climate change by accelerating soil C sequestration. However, little is known about ESW’s potential for success on global and regional scales. Applying basalt dust to soil can draw down atmospheric C, boost nutrient availability for crops, and counter soil acidification, yet it may also heighten microbial activity and release soil C via respiration. Arbuscular mycorrhizae (AM), ectomycorrhizae (EcM), and plant community composition can also alter weathering rates. Our research tests soil respiration rates in the presence of basalt dust and mycorrhizal associations in local Willamette Valley soils. We hypothesize that respiration will increase due to the fertilizing effects of basalt but that a faster pace of weathering will result in a net C sink. We predict that respiration and sequestration will be greatest in the presence of EcM fungi. To test this theory, we potted four tree species, each known to form an AM or EcM relationship, in soil mixed with none, low or high concentrations of basalt dust. We measured baseline soil pH, initial C stocks, and nutrients. Currently, we are measuring respiration using a soil CO2 flux chamber. As the project advances, we will measure changes to these variables, plant biomass, and inorganic C stocks. This study will contribute to the literature regarding the potential of ESW to offset anthropogenic C emissions.

Coursed-Grained Approach for the Protein Dynamics of the SARS-CoV-2 Spike Protein Variants

Presenter: Ruben Sanchez – Biochemistry, Biology

Faculty Mentor(s): Marina Guenza

Session: (In-Person) Poster Presentation

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) utilizes a spike protein to recognize the receptor protein Angiotensin-converting enzyme 2 (ACE2) of human cells to initiate COVID-19. It is known that the spike protein adopts an active (open) conformation from an inactive (closed) conformation to initiate its infectious cycle. But it is unknown whether the different variants have mutations that affect the protein dynamics of the spike protein. It was hypothesized that the amino acid mutations of more transmissible variants will have increased protein dynamics leading to a dramatized Monod-Wyman-Changeux model. Identifying and targeting these dynamics may lead to the development of pharmaceuticals that may inhibit the infectivity of the SARS-CoV-2 virus. Therefore, two variants of the spike protein were analyzed using molecular dynamic simulations and the Langevin Equation for Protein Dynamics (LE4PD) to quantitively analyze residue fluctuation within their respective spike proteins. LE4PD quantified the protein dynamics and demonstrated that the more infectious variants have higher fluctuations in their protein dynamics.

Evaluating Responsive Caregiving Behaviors within the FIND Intervention

Presenter: Heather Ralph – Biology, Psychology

Faculty Mentor(s): Andrea Imhof, Phil Fisher

Session: (In-Person) Oral Panel—Connection and Community

Interventions that emphasize responsive caregiving can reverse the negative effects of early life stress exposure on development in early childhood. Despite this knowledge, there is a lack of consensus in the field about which behaviors define “responsive caregiving”. The Filming Interactions to Nurture Development (FIND) Intervention is a responsive caregiving intervention that guides caregivers towards serve and return interactions that follows the child’s lead. Preliminary evidence from pilot trials suggest that the FIND intervention may significantly impact both caregiver and child outcomes, but it is not yet known how FIND changes the way caregivers and children interact. The purpose of this study is to evaluate whether FIND increases the frequency of caregiver “following” behaviors during a dyadic freeplay tasks. Results from a pilot trial using 18 mother-infant dyads (9 FIND families and 9 control families) will be presented, highlighting ways that the FIND intervention changes the nature of dyadic interaction. Implications for analyzing responsive caregiving behaviors, limitations, and next steps for evaluating the FIND intervention will be discussed.

Defining and Characterizing COVID-19 Quarantine Hesitancy in Lane County

Presenter: Marlee Odell – Biology

Faculty Mentor(s): Melissa Graboyes

Session: (In-Person) Oral Panel—Covering Covid

Contact tracing and subsequent quarantine of individuals exposed to COVID-19 has been a useful tool throughout the pandemic. While trying to implement such measures, however, it has become clear that some people are hesitant to agree to quarantine, for a variety of reasons. The term “hesitancy” appears in similar areas of public health such as with vaccine hesitancy, however, it has not been defined for COVID-19 quarantine hesitancy. Arising from personal experience as a contact monitor (CM) for the UO Corona Corps, this thesis intended to define COVID-19 quarantine hesitancy and to identify the determinants behind a contact’s hesitancy. Semi-structured, open-ended interviews were conducted with UO Corona Corps CMs about their experience with hesitant contacts. The interviews were thematically analyzed to reveal themes rooted in the firsthand experiences of CMs. This work suggests that COVID-19 quarantine hesitancy is when there is a discrepancy between public health officials’ recommendations and the actions of COVID-19 contacts. In addition, it suggests that there are multiple types of hesitancy and stages in the quarantine process in which they can arise. The thematic analysis also revealed three categories of COVID-19 quarantine hesitancy determinants: situational determinants, personal determinants, and quarantine comprehension. The results from this thesis can help inform future public health work that involves quarantine, whether for COVID-19 or other health issues.

Investigating the role of H3K9 methyl transferases in heat-induced DNA damage

Presenter: Philip Nosler – Biology

Faculty Mentor(s): Nicole Kurhanewicz, Diana Libuda

Session: (In-Person) Oral Panel—Bio-Zebrafish and DNA

Exposure to elevated temperature is a major cause of male infertility observed across both animals and plants. A primary consequence of heat stress is the accumulation of unusually high levels of DNA damage in developing sperm. Previous work from the Libuda Lab demonstrated that, similarly to humans, a single acute heat exposure is sufficient to produce high levels of DNA damage in developing sperm, but not in developing eggs in the model organism Caenorhabditis elegans. Further, mobilization of transposons, segments of DNA that can move autonomously throughout the genome, was associated with heat-induced DNA damage specifically in sperm. Normally, transposon movement is strictly repressed in the germline via chromatin modifications, which affect chromosome structure and regulate gene expression. Specifically, transposon genes are silenced in the germline via a particular chromatin modification: methylation of histone H3 lysine 9 by the methyltransferases SET-25, SET-32, and MET-2. Using an existing mutant strain for set-25 and a double mutant for met- 2;set-25, I found that DNA damage is elevated following heat stress, suggesting set-25 and met-2 repress heat-induced DNA damage. Currently, I am further assessing the roles of set-25, set-32, and met-2 in heat-induced DNA damage using single and double mutant strains. Overall, this work will further our understanding of the mechanisms underlying heat-induced male infertility.

Lrig3 is Required for Colonic Regeneration Following Acute Inflammatory Injury

Presenter: Kevin Mueller – Biology

Faculty Mentor(s): Anne Zemper, Janelle Stevenson

Session: (In-Person) Oral Panel—Daily Dose of Proteins

The mouse colon is a tightly regulated organ responsible for secreting mucus and absorbing water, which is carried out by colonic crypts; small U-shaped invaginations in the colon’s epithelial tissue. The excision of the protein Lrig3 has been characterized in homeostasis and is defined by more nuclei per crypt, increased mucosal area, and an expanded stem cell compartment consisting of more Lrig1+ cells per crypt. While we now understand that Lrig3 plays an important role in homeostasis, it is currently unknown what role Lrig3 might play in colon-based diseases. The disease we chose to test first was the mouse model of ulcerative colitis. Our lab treated two cohorts of mice, one Wild Type (WT) and one Lrig3-/-, with a 3% Dextran Sodium Sulfate (DSS) solution over 6 days to induce inflammation. Both cohorts were allowed to recover for 24 hours before analysis. We found Lrig3-/-mice are more susceptible to DSS treatment and lack the colonic regenerative capability seen in WT mice. We then performed immunohistochemistry, dye, and enzymatic-based analyses to examine the expression profiles of proteins associated with regeneration of the colonic epithelium. We observed a decrease in cells expressing the stem and progenitor marker Lrig1 in Lrig3-/- mice compared to WT (p<0.01) and a decrease in the total cell number per crypt (p<0.001), however there was no change in proliferation. These data suggest Lrig3 is required for epithelial regeneration in DSS- modeled ulcerative colitis.

Maternal opioids decrease neonatal opioid receptor expression in brain regions controlling breathing

Presenter: Emilee McDonald – Biology

Faculty Mentor(s): Adrianne Huxtable, Robyn Naidoo

Session: (In-Person) Poster Presentation

An understudied population in the opioid crisis are infants exposed to maternal opioids experiencing breathing deficits. Our animal model of maternal opioids demonstrated neonatal breathing deficits after birth, which normalized with age despite continued maternal opioid exposure, suggesting neonatal compensation to this early life opioid stressor. To understand the mechanisms of these breathing deficits, we tested the hypothesis that maternal opioids decrease opioid receptor expression (since opioids activate opioid receptors to exert their effects) in a key brainstem site for breathing. Brainstem immunohistochemistry and confocal microscopy assessed typical developmental changes in neonatal opioid receptor expression after maternal no treatment (control). Opioid receptor expression was highest at postnatal day 0 (P0), when neonates begin breathing, and decreased through P11, a critical maturation period of the nervous system. In neonates after maternal opioids, opioid receptor expression was evaluated at P0 (birth), P4 when neonates still receive opioids through breast milk, and P11 after opioid exposure has ceased. Preliminary data support decreased opioid receptor expression in P0 and P4 neonates after maternal opioids, but a return to control levels at P11. Thus, maternal opioids acutely impair opioid receptor expression in a brainstem site critical for breathing, suggesting opioid receptors may be key to neonatal breathing impairments after maternal opioid exposure.

The Effects of daf-2/IGFR on Healthspan in C. elegans Males

Presenter: Hannah Lewack – Biology

Faculty Mentor(s): Rose Al-Saadi

Session: (In-Person) Poster Presentation

Neurodegenerative diseases affect 50 million Americans each year and Alzheimer’s alone affects about 5 million. Alzheimer’s places a substantial economic burden on our healthcare system, estimated to be 305 billion dollars in 2020. Despite this cost, knowledge of the molecular mechanisms that contribute to healthy aging remains limited. We believe that a key to addressing this gap lies in Caenorhabditis elegans nematodes. Male C. elegans have 91 sex-specific neurons that are necessary for reproduction, allowing successful mating to be a good indicator of neuronal health. This system has been used to identify several pathways and genes that regulate aging, including the insulin-like growth factor 1 receptor daf-2. Our findings show that mutations in daf-2 result in extended lifespan, and slow the decline of male mating ability at old age. Due to the ubiquitous expression of daf-2, its role in male mating is difficult to associate with specific tissues. The auxin-induced degron (AID) system allows for targeted degradation of proteins in a spatially and temporally-controlled manner. Using this system, we will test the effects of DAF-2 degradation in the intestinal, neuronal, and hypodermal cells on male mating success. Due to DAF-2 mutant’s extension on lifespan, we hypothesize that DAF-2 degradation in tissues will delay age-induced mating decline. This project will give additional insights to the importance of the metabolic pathway and its impact on neuronal functions.