HNSE-P9-5. Effect of Mutations of Ciliary Genes within Cancers

Richard Gu1, 2
Van Vo, Ph.D.3
Faculty Research Mentor: Edwin Oh, Ph.D.3
1College of Sciences, Department of Chemistry and Biochemistry
2Howard R. Hughes College of Engineering, Department of Computer Science
3Nevada Institute of Personalized Medicine

Primary cilia are small hair-like organelles that are expressed in various types of mammalian cells. Their function is to gather information about their environment and induce a functional response in nearby cells. Defects in primary cilia can lead to diseases/disorders in humans, known as ciliopathies. Some ciliary proteins have been associated with the development of cancer. To better understand the association between primary cilia and cancer, online databases were used to investigate the alterations of ciliary genes in different cancers. A list of ciliary genes was compiled utilizing the CiliaCarta database, which is a validated compendium of ciliary genes. The list of ciliary genes was then searched in cBioPortal, a cancer database that allows for analysis of large-scale cancer genomics data sets, to determine if there are mutations/changes in expression of these ciliary genes in different cancers. Various protein changes and mutations of ciliary genes such as IFT88, IFT57, TUBB3, and TRAF3IP1 were identified in cancers such as glioblastoma, pediatric ewing sarcoma, and colorectal adenocarcinoma. Through further analysis, missense mutations were the most prevalent followed by splice mutations. By identifying the types and locations of these mutations, we can further investigate how mutations of specific ciliary genes contribute to a particular cancer through using cancer cells or animal models.

HNSE-P9-4. Genes Potentially Related to Pcm1

Nabih Ghani1
Chinglan Chang1
Faculty Research Mentor: Edwin Oh, Ph.D.1
1College of Sciences, Department of Life Sciences
2College of Liberal Arts, Department of Psychology
3Nevada Institute of Personalized Medicine

The primary cilium is an important organelle in mammalian cells that plays a role in cell signaling and development. Problems with the function of primary cilia in cells are linked with many disorders that are collectively known as ciliopathies. Pericentriolar Material 1 (Pcm1) is a gene that plays an important role in the functioning of primary cilia. The goal of this project was to find genes that show phenotypes similar to Pcm1 when knocked out in mice. Using the International Mouse Phenotyping Consortium (IMPC), a database that houses data about knockout genes and their associated phenotypes in mice, we found nine phenotypes associated with a knockout mouse model of Pcm1. Then, using the IMPC database, we were able to identify genes associated with each phenotype and compiled and analyzed the data in Excel. During the summer, the analysis of the data revealed three genes that when deleted in mice shared six of the nine phenotypes associated with the Pcm1 knockout mouse. The three genes were Dnase1l2, Slc20a2, and Sparc. The IMPC database is often updated and performing this analysis after the updates will help identify more potential genes that mimic the loss of Pcm1. By identifying these genes, we can find new avenues for research that are associated with our gene of interest.

HNSE-P9-3. Diverse Viral UDG-fused DNA Polymerases in Metagenomes from Geothermal Springs and Possible Role in Coupled Nucleotide Repair and Replication

Ryan Doss1, 2
Brian Hedlund, Ph.D.1
Marike Palmer, Ph.D.1
Faculty Research Mentor: Philippos Tsourkas, Ph.D.1
1College of Sciences, Department of Life Sciences
2College of Sciences, Department of Chemistry and Biochemistry

High temperature exerts strong selective pressures on macromolecular structure, imparting well-characterized thermophilic adaptations to DNA, RNA, protein, and lipid structures. However, despite the low thermal stability of many monomers that are the building blocks of these macromolecules, biochemical adaptations to mitigate the instability of monomers in thermophiles are poorly studied. Here, we explored viral contigs obtained from metagenomes from a variety of high-temperature geothermal springs and describe an unusual fusion of a Uracil-DNA-glycosylase (UDG) domain to DNA polymerase I. UDG enzymes can excise uracil from DNA, allowing for the repair of uracil-DNA caused by the deamination of cytosine. A fusion to DNA polymerase, can mean UDG would be able to act in tandem with the polymerase, allowing for higher fidelity thermostable DNA synthesis and a possible advantage when compared to other viruses without UDG function. To determine how abundant these sequences are in thermal environments, metagenomes and single-cell genomes from the Integrated Microbial Genomes Database were interrogated to identify UDG-DNA polymerase fusion proteins. These genes were then characterized based on their protein domains using the NCBI Conserved-Domain Database and the Interpro protein database, to confirm that both functions were predicted. Multiple sequence alignments of the proteins were obtained with MAFFT/DASH, and similarity matrices and maximum-likelihood phylogenies were constructed. Two large sequence clusters (> 8 sequences) and 11 medium sequence clusters (3-7 sequences) were identified.The viral contigs comprising the UDG-DNA polymerase clusters will be further interrogated to determine their evolutionary relatedness, distribution, and abundance in thermal environments.

HNSE-P9-2. PyXtal-FF an Automated Python Library for Force Field Construction

David Zagaceta1, 2
Hoawrd Yanxon1, 2
Faculty Research Mentor: Qiang Zhu, Ph.D.1
1College of Sciences, Department of Physics and Astronomy
2College of Sciences, Department of Mathematical Sciences

We introduce a new chemical physics software library, based on the python programming language, that can automatically generate atomistic force fields from data consisting of the energies and forces experienced by atoms, as derived from quantum mechanical calculations, using techniques from representation theory and various machine learning techniques. Specifically, we utilize methods of harmonic analysis to generate so-called “invariant features” to use as input to a regression model (usually a neural net or a polynomial regression) to predict atomic energies, forces and stresses.

HNSE-P9-1. Measurement of the Energy Dependence of X‐ray-Induced Decomposition of Nucleobases

Kevin Ayala Pineda1
Petrika Cifligu1
Faculty Research Mentor: Michael Pravica, Ph.D.1
1College of Sciences, Department of Physics and Astronomy

With the developing field of useful hard x-ray induced chemistry, x-rays offer unique chemical pathways leading to novel synthesis and decomposition. In the crisis of the coronavirus COVID–19 and the urgency of creating a high-quality vaccine, here we present preliminary results that aims at utilizing hard x-rays to denature a virus with minimal damage to the capsid (protein coat), and thus target the DNA/RNA. For this study, we irradiated two nucleobases, adenine and uracil, via hard x-rays at selected energies. X-ray diffraction patterns and far-infrared data’s were then taken and analyzed for the decomposition of the material. Results from uracil suggest possible decomposition.

HNSE-P8-6. C-terminal Variants Associated with Disease

Zachary FitzHugh1, 2, 3
Xiaogang Wu4
Faculty Research Mentor: Martin Schiller, Ph.D.5
1Howard R. Hughes College of Engineering, Department of Computer Science
2Lee Business School, Department of Economics
3College of Sciences, Department of Mathematical Sciences
4Nevada Institute of Personalized Medicine
5College of Sciences, School of Life Sciences

This research investigates the extent to which pathogenic mutations are located on the C-termini of proteins in the human proteome. Proteins are directionally translated from the N-terminus to the C-terminus. We define C-terminus for the purposes of the project as being the last ten amino acids in a protein. There are eight pathogenic C-termini mutations supporting our hypothesis that many other mutations on C-termini may cause human disease. We addressed this hypothesis by analyzing existing data sets from the National Center for Biotechnology Information (NCBI), the Broad Institute of MIT and Harvard, UniProt, dbNSFP, and the Schiller Lab. NCBI’s RefSeq database and ClinVar database were especially important. Research began with identifying all of the proteins recorded in RefSeq. From there, we determined the amino acid sequences of their respective C-termini. We then ascertained which variants in ClinVar change an amino acid on a given C-terminus. These variants were matched where possible to their corresponding entries in the Broad Institute’s gnomAD data and in the dbNSFP annotation database to assess variant frequency and GERP scores, respectively. The resulting data set records C-termini variants by category of pathogenicity, the frequency of pathogenic variants, the diseases caused by the variants, the genes that possess pathogenic variants, and evolutionary conservation. We additionally analyze how C-termini variants disrupt minimotifs, short amino acid chains in a protein that perform a specific function, using the Schiller Lab’s C-Terminome database and the UniProt database. Data collection and analysis were performed using custom Python scripts.

HNSE-P8-5. Structure and Bandgap of O-incorporated CsPtI3 Halide Perovskites

Kristen Tagaytayan1
Faculty Research Mentor: Shubhra Bansal, Ph.D.1
1Howard R. Hughes College of Engineering, Department of Mechanical Engineering

Halide perovskite materials have shown significant promise for low-cost, high-efficiency photovoltaic devices due to their excellent optoelectronic properties and tunable bandgap. However, the toxicity of Pb and poor stability of MAPbI3 has proven to be a challenge for the commercialization of this technology. Alternate Pb-free halide perovskites need to be developed to address these challenges. Here, we study the structure and optical properties of O-containing CsPtI3 and Cs(PtNi)I3 mixed halogen-chalcogen perovskite materials. The effect of the addition of guanidinium thiocyanate (GuaSCN) additive is also discussed on the structure and bandgap of the material. The solution-processed CsPtI3 was deposited via doctor blade coating method. Nickel was added at a precursor ratio (Pt:Ni) of 50:50, and 5%, 10%, and 20% GuaSCN was added to the precursor solution. O-containing CsPtI3 perovskites had direct bandgaps of ~2.1 eV. With the addition of nickel, the bandgap can be tuned to ~1.52 eV while the addition of GuaSCN narrows the bandgap to 1.2–1.3 eV. This bandgap tuning achieved by solvent engineering can open the possibility of forming perovskite-perovskite tandem cells using these promising Pb-free compositions.

HNSE-P8-4. The Optimization of a Signed Tree

Janelle Domantay1
Alvaro Carbonero2
Karen Guthrie11
Faculty Research Mentor: 2, 3
1Howard R. Hughes College of Engineering, Department of Computer Science
2College of Sciences, Department of Mathematical Sciences

A signed graph G is a regular graph where each edge is assigned a + (positive edge) or a – (negative edge). The signed degree of a vertex v in a signed graph, denoted by sdeg(v), is the number of positive edges incident to v subtracted by the number of negative edges incident to v. Finally, we say G realizes the set D if: D = {sdeg(v) : v ∈ V(G) }.
In this paper we prove that D is the signed degree set of a tree if and only if 1 ∈ D or -1 ∈ D. Further, for every valid set D, we find the smallest diameter that a tree must have to realize D. Lastly, for valid sets D with nonnegative numbers, we find the smallest order that a tree must have to realize D.

HNSE-P8-3. The History of Fragile X Syndrome

Louie Zendejas1
Luis Burgos Banchs1
Erika Vaca Lopez1
Faculty Research Mentor: Kathryn Rafferty, Ph.D.1
1College of Sciences, School of Life Sciences

The purpose of this research is to investigate the discovery, social impact, and evolution of Fragile X Syndrome (FXS). Fragile X syndrome, previously known as Martin-Bell syndrome, was discovered by J. Purdon Martin and Julia Bell in 1943. It is a non-mendelian, X-linked dominant genetic disorder that causes mild to severe intellectual disabilities and abnormal physical features. FXS is characterized by the expansion of the Fragile X Mental Retardation (FMR1) gene with more than 200 CGG triplet repeats in the promoter. The research of FXS was slow until a 1991 study led to the discovery of the CGG repeats in the FMR1 gene promoter. Males are more likely to have the FMR1 expansion, which leads to FXS. The FMR1 expansion leads to gene silencing, which inhibits the production of the fragile X mental retardation protein (FMRP) that is known for protein regulation and synapse development. The manifestation of the disease is seen in childhood and has variable expressivity. The current treatments for the disorder are behavior therapies and medications for the mood disorders. Current research focuses on diseases caused by premature FMR1 mutations, in which there are 55-200 repeats. Currently, there is no cure for the disorder and the median cost per patient with FXS with no hospitalizations is between $1614 to $3064 annually. A possible prevention for FXS could be genome editing with the use of CRISPR-Cas9. The significance of this timeline is to understand FXS and identify the ways that treatments could be developed in the future.

HNSE-P8-2. Coronary Artery Disease (CAD) in Asian Populations

An Truong1, 2
Sijia Li1
Faculty Research Mentor: Kathryn Rafferty, Ph.D.1
1College of Sciences, School of Life Sciences
2College of Liberal Arts, Department of Psychology

The purpose of this research timeline is to synthesize the natural history of Coronary Artery Disease (CAD) to discover the gaps in knowledge and develop a public health message. CAD is the blockage of coronary arteries that causes atherosclerosis, which is a buildup of fatty plaque within the arteries. The earliest discovery of CAD was back in 1938, when scientists discovered hereditary patterns in familial hypercholesterolemia, a premature form of CAD. Currently, scientists have identified CAD as a complex multifactorial disease that has numerous possible biological pathways leading to the disease; including inflammation, lipid metabolism, folate metabolism, oxidative stress, DNA damage, Renin-angiotensin pathways. However, the primary cause of CAD is still unknown. This research will focus on the mutation on 9p21 locus. Unlike other genetic mutations, mutations on 9p21 are independent from other clinical risks, such as lipid metabolism and insulin level. Treatments for CAD currently include medications such as statin, anticoagulants, β-blockers, and calcium channel blockers that help in effectively preventing the onset of the disease.

CAD is one of the most common causes of death, killing around 500,000 individuals annually. Asian populations have a higher prevalence for CAD, due to more prominence in the 9q21 SNPs. In addition to that there are environmental factors that contribute to the early onset, including poor/fatty diets, sedentary lifestyles, and smoking. Scientists continue to progress in research to further their understanding of the disease. This project utilizes literature reviews to indulge into the history of CAD and how certain populations are affected.