ABSTRACTS
2019 National McNair Scholars Conference at UCLA
Researcher: Jonathan Do
Presentation Title: Is Replication Stress-Induced Nucleophagy Controlled by Multiple Pathways?
Research Focus: Cellular and Molecular Biology
School: UC Davis
Presentation Type: Oral Presentation
Mitosis is a highly regulated process such that each daughter cell receives identical genomes. Genome stability requires constant coordination of chromosome replication and segregation elements. The final steps in this process include the resolution of sister chromatids and completion of DNA replication. To ensure stability, nuclear envelope formation is suppressed until segregated sisters have been properly resolved. The premature packaging of chromatids into a nucleus gives rise to micronuclei and subsequent genomic instability. The mechanisms that suppress micronuclei are unclear, though it has been proposed that nucleophagy, a type of autophagy, may play a role. Consistent with this idea, we have seen that DNA replication stress activates nucleophagy in budding yeast and that this pathway requires the intra-S-phase checkpoint kinases. We hypothesize that nucleophagy induced by replication stress involves the activation of two parallel pathways such as the intra-S-phase checkpoint kinases and Tor-regulated autophagy program. We predict that each pathway will control discrete steps in the replication stress-induced nucleophagy response. To test this, I will use cell-based assays developed in the Kaplan lab and test how mutations in these pathways impact nucleophagy. I predict that mutations in both pathways will compromise nucleophagy and lead to genomic instability after replication stress.
Maternal care is known to influence behavior in many species and discrepancies in behavioral abnormalities between kittens raised in foster homes and those receiving direct maternal care, may lead to issues that jeopardize welfare and development. There is indication that maternal interactions involving nursing and weaning have far reaching effects on behavioral and physical development of neonatal kittens. One such behavior routinely observed in foster homes and shelters has been found to pose a concern to the health of kittens: non-nutritive suckling. In this observational study, video footage of orphaned neonatal litters raised and bottle-fed by foster caretakers was assessed to identify significant correlations between the prevalence of non- nutritive suckling (oral contact to different surfaces, usually littermates, that is not for the purpose of consumption) and quantified time allocating to sleeping and activity. This was done to identify the magnitude of the exchange driven by the motivation to engage in suckling behaviors during typical sleeping periods. Additionally, supplement data sets received through an online survey and footage from UNAM provide complementary information to temporal patterns associated with sucking in these populations. By observing the possible relationship between neonatal suckling due to a lack of a maternal presence, as well as the direct effects on activity level and sleep, we can further examine additional ramifications rearing by human hands may have on development of abnormal behaviors in these populations, and perhaps how to better address the welfare issue it poses.
Researcher: Rebecca Rafique
Presentation Title: Probing the Hydrogen Bond Network in FUS Fibril Assemblies
Research Focus: Biophysical Chemistry, Structural Biology
School: University of California, Davis
Presentation Type: Oral Presentation
A main characteristic for those diagnosed with Amyotrophic Lateral Sclerosis (ALS) is the buildup of aggregates of the fused in sarcoma (FUS) protein in nerve tissues. The FUS protein exists in at least two distinct chemical phases: a functional liquid droplet-like phase where FUS is structurally dynamic and a pathogenic aggregated phase where FUS adopts a rigid fibril structure. In ALS, genetic mutations in FUS favor the aggregated phase over the liquid droplet phase by stabilizing the fibril conformation. Unlike most proteins, the FUS primary sequence is heavily biased toward a subset of the twenty amino acids and is highly enriched in polar amino acids. The fibril structure appears to be stabilized by hydrogen bond interactions between polar residues instead of the hydrophobic interactions typically observed in other pathogenic protein fibrils. We hypothesize that an intramolecular hydrogen bond network stabilizes the 3D fold of FUS in fibril form. To test this idea, we are systematically mutating amino acids in the FUS primary sequence to disrupt the potential hydrogen bond network. Nuclear magnetic resonance and calorimetry measurements will quantitatively probe changes in structure and thermodynamic stability that result from our engineered FUS mutants. Our measurements will reveal the nature of the molecular interactions that stabilize the FUS fibril conformation. The data will be useful to understand how ALS-linked mutations in the FUS protein favor the formation of fibrils, consequentially allowing us to have a better understanding of ALS disease pathology.
Researcher: Andrew Ramirez
Presentation Title: Angiogenic Therapeutics for the Treatment of Peripheral Ischemia in Diabetic Foot Ulcers
Research Focus: Biomedical Engineering
School: University of California, Davis
Presentation Type: Oral Presentation
Fifteen to twenty-five percent of diabetics develop chronic foot ulcers in their lifetime characterized by delayed wound healing. This impaired healing is caused due to ischemia resulting from poor blood vessel perfusion which results in peripheral limbs not obtaining enough blood circulation. To improve healing, researchers have sought to increase angiogenesis at the wound site, along with reducing the matrix turnover of the tissue. In an effort to treat multiple derangements, we propose the use of a molecule composed of a collagen binding peptide (SILY) and an integrin binding peptide (LXW7) conjugated to a dermatan sulfate (DS) backbone to form LXW7-DS-SILY. This molecule will specifically target the collagen-exposed wound bed and protect it from degradation, along with binding receptors on endothelial cells to activate the vascular endothelial growth factor (VEGF) pathway. After synthesis and characterization of the molecule, we will assess the in vitro and in vivo angiogenic potential of the molecule by testing its ability to bind to collagen, and its ability to stimulate blood vessel formation in a chick chorioallantoic membrane model. In the future, we hope to test this molecule in a diabetic in vivo animal model to assess the efficacy of our proposal.
Researcher: Sarina Rodriguez
Presentation Title: Access & allocation of healthcare services in Knights Landing, CA: An assessment of rural representation in community health needs assessments
Research Focus: Public Health Policy
School: UC Davis
Presentation Type: Oral Presentation
Knights Landing is an unincorporated rural town within the agriculturally-dominated Yolo County. Current health access needs of Knights Landing are not accurately represented in local health research compared to larger cities in Yolo County (i.e. Woodland and Davis). Based on our Access to Care Survey conducted between 2017 and 2018 in Knights Landing, the major barriers to healthcare and the needs of this community differ from the most recent community health needs assessments conducted by local government and healthcare providers. Resource allocation and relative population sizes are likely contributors to why regional health needs assessments are more likely to represent the needs of the wealthier and urbanized cities versus poor rural cities. This study will investigate how discrepancies between local health officials’ assessment of need impact access to primary healthcare in unincorporated rural communities. These results will be used to analyze the effectiveness of potential solutions in progress by the county compared to ongoing private, nonprofit, institutional, and community-based interventions in Knights Landing.
Researcher: Diana Santoyo
Presentation Title: Bilingualism and Executive Functioning: Emerging Bilinguals in Head Start
Research Focus: Bilingualism and Executive Function
School: University of California, Davis
Presentation Type: Oral Presentation
The relationship between bilingualism and executive function has shown mixed results. Children’s metalinguistic awareness has been displayed as an advantage of bilingualism, which serves as indicators of executive function (EF) systems (Bialystok, 2015). Yet, others have found no bilingual advantage in EF (Paap, Johnson, & Sawi, 2015). The aim of this study is to examine the association between language proficiency in the dominant and nondominant languages of Spanish and English and Cantonese and English and the EF components of inhibitory control and cognitive flexibility with emerging Spanish-English and Cantonese-English bilingual preschoolers enrolled in Head Start programs. In this study, bilingualism will be defined by performance on the Woodcock Johnson Picture Vocabulary, Oral Comprehension, and Understanding Directions, while EF will be measured with the NIH Tool Box (Flanker and Card Sort) and Head-Toes-Knees-Shoulders Task. Data is being collected from Mexican-American and Chinese-American preschoolers attending Head Start programs in Northern California.
Preliminary results show that although they are low on average in oral proficiency in both their home language and English, their NIH toolbox scores suggest that on average they score similar to their monolingual-English speaking peers on EF tasks. The relationships among EF and bilingualism will further be explored.
Researcher: Rachelle Stowell
Title: Structural and Thermodynamic Characterization of TIA1 Protein Fibrils
Research Focus: Biophysical Chemistry
School: University of California, Davis
Presentation Type: Oral Presentation
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurodegenerative diseases that are poorly understood with no effective treatments. Mutations in the T cell-restricted intracellular antigen-1 protein (TIA1) linked to ALS and FTD correlate with an increased incidence of pathogenic fibrillar aggregates in patient tissue, similar to the buildup of amyloid plaques observed in Alzheimer’s patients. TIA1 is an RNA-binding protein that is essential for the formation of RNA stress granules, micron sized structures that protect cells in disease conditions. Pathogenic fibrillar assemblies of TIA1 are thought to form out of the RNA granule structures. In this study, we produced the TIA1 protein using a recombinant bacterial expression system, obtained milligram quantities of the protein, and have purified it to greater than 95% purity. The recombinant protein is being used to provide an atomic-resolution molecular basis for understanding pathogenic fibril formation by TIA1. We prepared TIA1 fibrils and used transmission electron microscopy to visually characterize their appearance. We are currently employing calorimetry to measure the thermodynamic stability of TIA1 in the fibril form and solid state nuclear magnetic resonance to characterize the fibril structure. The thermodynamic and structural measurements on the TIA1 assemblies will provide insight into the transition into pathogenic structures out of functional RNA stress granule structures in relation to ALS and FTD. Our results will provide a better understanding of these devastating diseases and will guide the design of new treatments and early detection imaging agents.
Researcher: Debbie Sulca
Presentation Title: Using Mobile Air Sampling to Measure Potential Exposure Hazards to Kettleman City’s Residents
Research Focus: Environmental Toxicology
School: University of California, Davis
Presentation Type: Oral Presentation
California’s Kettleman City is surrounded by commercial agriculture, a class I hazardous landfill, benzene treatment plants, and the California aqueduct. These industries may emit volatile organic compounds (VOCs) into the air, which pose severe environmental threats to residents. This current study aims to examine air quality in this socioeconomically disadvantaged community and understand the perceptions its predominantly Spanish-speaking residents have about their environment. To measure air quality, a custom built, micro-gas preconcentrator (µPC) sampler was used to adsorb VOCs in the air. Samples were collected in multiple locations: a bathroom with cold running water to identify potential dissolved VOCs released into the indoor air; other indoor locations in a residence; outdoor locations near a potentially polluted intersection. Samples were analyzed using gas chromatography-mass spectrometry (GC-MS) to putatively identify and quantify the presence of VOCs in the collected samples. Chemical analyses revealed potential toluene, xylene, and benzene derivatives in the outdoor air samples, and potential tribromomethane in the indoor bathroom air sample. An environmental health survey was deployed door-to-door to every household (N=300). Findings include residents’ concerns related to air quality, water quality, and pesticides. Implications of this study demonstrate the importance of research to understand environmental injustices experienced by residents of California.
Researcher: Monica Velazquez
Presentation Title: Sacramento and Oakland: Traditional Latin American Medicine in California
Research Focus: Public health
School: University of California, Davis
Presentation Type: Oral Presentation
Traditional medicine in Latin America is the usage of natural substances, a variation of herbs and ointments, for the purpose of healing. Traditional medicinal practices differ throughout the regions and populations of Latin America. Throughout Latin America traditional medicine is practiced differently varying by region and population. My study primarily focuses on traditional medicinal practices in the United States. Specifically, I take a look at traditional healers known as curanderos in the Sacramento and Oakland area. The purpose of this study is to identify the healing methods used by curanderos for their patients. In the California Latino community traditional healing is often times sought after more than western medicine. Through a preliminary study I previously conducted traditional healing is used most by Latino immigrants or Latinos of low socioeconomic status. In California only 26% of Latinos have medical insurance despite federal law stating it is mandatory to be enrolled into a healthcare plan.
Therefore, Latinos who are not eligible for a healthcare package due to legal status or being unable to afford a healthcare plan use traditional medicine as their primary coverage. An in depth study of traditional medicine can lead to its integration into western medical practices. With the possibility of integration between western and traditional medicine in California, this study also looks at Bolivia’s healthcare system where there has been an integration of western and traditional medicine.
Researcher: Dawn Warfield
Title: How genome-wide association studies of educational attainment reify eugenic ideologies
Research Focus: Philosophy/History & Philosophy of Science
School: University of California, Davis
Presentation Type: Oral Presentation
In the late 19th century, proto-geneticist statisticians like Francis Galton founded the field of eugenics to encourage research on biological inheritance of intelligence, developing statistical models of heredity that continue to serve as important analytical tools for modern behavior economics. In the 21st century, new techniques in molecular biology renewed the search for biological explanations of human behavior and potential centered on the correlation of genetic data with experiential outcomes of cohort members in longitudinal studies. Genome-wide association studies (GWAS) analyze a selected set of single nucleotide polymorphisms (SNPs) across sample populations to correlate genotype variations to identify phenotypes that may be associated with health and behavior. Between 2013 and 2018, three GWAS explored the genomic correlates of educational attainment. As these studies grew in size from just over 100,000 participants in 2013 to over 1.1 million in 2018, the number of SNPs found to be statistically associated with educational attainment expanded from 3 to 1,271. My talk will discuss these recent studies as part of a longer history of research into the genetic determinants of intelligence and ability, asking why and how they were done, and what claims have been made on the basis of their findings. I will focus on the role of academic and commercial research in completing GWAS, and on the interpretation of their results by academics, commercial entities, and the media.
Researcher: Tiana Williams
Presentation Title: Forgotten Radicals: The Legacy of the United States Prisoners’ Rights Movement
Research Focus: The 1970s Prisoners’ Rights Movement
School: University of California, Davis
Presentation Type: Oral Presentation
In recent years, there has been an increasing discourse centered on the prison-industrial complex, addressing issues that range from ending the school-to-prison pipeline to calls for the abolition of prisons entirely. However, this movement is far from a novelty, rather, it is the resurgence of a forgotten moment in history that is being revitalized through a different lens. It is important to provide context to these current conversations and ensure that the prominent lens utilized for such discussions is that of the prisoner’s rights movement. With primary and secondary sources, archival footage and a collection of oral histories, the research will examine the ways in which the prisoner’s rights movement fueled hostility that produced negative systemic backlash and a present-day declension narrative. By highlighting prisoner activism of the 1970s, this article challenges the declension hypothesis approach to the prisoner’s rights movement and investigates the movement’s effects on the current day structure of the criminal justice system.