Biochemistry, Biophysics, and Structural Biology Commons^™

Dna Methylation And The Response To Infection In Introduced House Sparrows, Melanie Gibson

College of Graduate Studies: Theses & Dissertations

Epigenetics is the study of molecular modification of a genome without changing its base pairs. The most studied type of epigenetic mechanism is DNA methylation, which is capable of turning a gene “on” or “off.” Epigenetic potential is the capacity to which an individual can have methylation on its genome. The more CpGs available, the greater the epigenetic potential. In invasive species, genetic variation has been observed to be paradoxical: not much of it exists on a genomic level, but epigenetically, phenotypic variation can occur. The focus on shift in gene expression in this study is on Toll-Like Receptor 4 …

Structure–Activity Relationship Studies On 6-Chloro-1-Phenylbenzazepines Leads To The Identification Of A New Dopamine D1 Receptor Antagonist, Rajan Giri, Hari K. Namballa, Vishwashiv Emogaje, Wayne W. Harding

Publications and Research

The 1-phenylbenzazepine template has yielded a number of D1R-like ligands, which, though useful as pharmacological tools, have significant drawbacks in terms of selectivity versus D5R as well as pharmacokinetic behavior. A number of 1-phenylbenzazepines contain a 6-chloro functional group, but extensive SAR studies around the 6-chloro-1-phenylbenzazepine framework have not been reported in the literature. To further understand the tolerance of the 6-chloro-1-phenylbenzazepine template for various substituent groups towards affinity and selectivity at D1R, we synthesized two series of analogs with structural variations at the C-7, C-8, N-3, C-3′ and C-4′ positions. The series 2 analogs differed from …

Effects Of Depth, Distance To Shore, And Water Velocity On Organismal And Extra-Organismal Environmental Dna Concentrations In A Large River, Dylan Keel

Cal Poly Humboldt theses and projects

Environmental DNA (eDNA) is a sensitive tool for detection of aquatic species and concentrations of eDNA in water samples have been useful for estimating abundance. This study evaluated the effects of depth, distance to shore, and water velocity on the concentration of organismal and extra-organismal eDNA concentrations in the Klamath River, California (basin area ≅ 40,000 km²). At each of six river cross sections 32 water samples were collected, including surface samples and depth samples evenly distributed across the cross section, and eDNA concentrations were determined for the parasite Ceratonova shasta and Chinook salmon, Oncorhynchus tshawytscha, using …

Plastic Recognition And Electrogenic Uniport Translocation Of 1st-, 2nd-, And 3rd-Row Transition And Post-Transition Metals By Primary-Active Transmembrane P1b-2-Type Atpase Pumps, Sameera S. Abeyrathna, Nisansala S. Abeyrathna, Priyanka Basak, Gordon W. Irvine, Limei Zhang, Gabriele Meloni

Department of Biochemistry: Faculty Publications

Transmembrane P-type ATPase pumps catalyze the extrusion of transition metal ions across cellular lipid membranes to maintain essential cellular metal homeostasis and detoxify toxic metals. Zn()-pumps of the P-type subclass, in addition to Zn , select diverse metals (Pb, Cdand Hg) at their transmembrane binding site and feature promiscuous metal-dependent ATP hydrolysis in the presence of these metals. Yet, a comprehensive understanding of the transport of these metals, their relative translocation rates, and transport mechanism remain elusive. We developed a platform for the characterization of primary-active Zn()-pumps in proteoliposomes to study metal selectivity, translocation events and transport mechanism in real-time, …

The Role Of Myocardin In The Progression Of Non-Small Cell Lung Cancer, Soromidayo Akinsiku

Biotechnology Theses

Lung cancer is the leading cause of cancer-related mortality in the world and NSCLC accounts for 85% of all lung cancer cases. The mainstay of treatment for patients with stage I, II and IIIA NSCLC is surgery, followed by post-operative cisplatin-based chemotherapy. Additional adjuvant therapy involving targeted tyrosine kinase inhibitors has been in use, however even for the targeted therapy, resistance eventually develops. Therefore, there is a need for identifying novel targets for this life-threatening disease. Given that preliminary studies in Ikebe lab revealed that myocardin knockdown significantly promoted caspase-3 degradation, in this study, using myocardin siRNA, we investigated the …

การเกิดภาวะพหุสัณฐานทางพันธุกรรมของยีนในวิถีวิตามินดีและความเสี่ยงต่อภาวะออทิซึมสเปกตรัมในประชากรไทย, ชาญณรงค์ แซ่ฉั่ว

Chulalongkorn University Theses and Dissertations (Chula ETD)

กลุ่มอาการออทิซึมสเปกตรัม (Autism spectrum disorder; ASD) เป็นปัญหาสุขภาพระดับโลกที่สำคัญ โดยพบว่ามีความชุกของโรคที่เพิ่มสูงขึ้น อย่างไรก็ตามสาเหตุและกลไกในการเกิดภาวะออทิซึมสเปกตรัมยังไม่ทราบแน่ชัดอาจเกี่ยวข้องกับปัจจัยด้านพันธุกรรมและสิ่งแวดล้อม โดยปัจจุบันมีรายงานถึงบทบาทของวิตามินกับภาวะออทิซึมสเปกตรัม วัตถุประสงค์ของการศึกษานี้คือศึกษาการเกิดภาวะพหุสัณฐานทางพันธุกรรมของยีนในวิถีเมทาบอลิกของวิตามินดีและความเสี่ยงต่อการเกิดภาวะออทิซึมสเปกตรัมและระดับความรุนแรงของโรคในเด็กไทย การศึกษานี้มีจำนวนอาสาสมัคร 276 ราย โดยเป็นกลุ่มเด็กที่มีภาวะออทิซึมสเปกตรัม 169 ราย และกลุ่มควบคุมเป็นเด็กที่ไม่มีโรคทางระบบประสาท 107 ราย ซึ่งได้ทำการตรวจวิเคราะห์ภาวะพหุสัณฐานทางพันธุกรรมของยีน CYP2R1, CYP27B1, GC และ VDR โดยเทคนิค TaqMan-based real-time Polymerase Chain Reaction (PCR) และตรวจวิเคราะห์ระดับวิตามินดีในกระแสเลือดโดยใช้เทคนิค Chemiluminescence Immunoassay (CLIA) โดยเด็กที่พบภาวะออทิซึมสเปกตรัมจะได้รับการตรวจระดับความรุนแรงของภาวะออทิซึมสเปกตรัมด้วย Childhood Autism Rating Scale, 2nd Edition (CARS2) โดยผลที่ได้จากการศึกษาพบว่า การเกิดภาวะพหุสัณฐานทางพันธุกรรมของยีน CYP2R1, CYP27B1, VDR และ GC (rs4588) ไม่มีความสัมพันธ์กับการเกิดภาวะออทิซึมสเปกตรัมและความรุนแรงของอาการออทิซึมสเปกตรัม อย่างไรก็ตามการศึกษาชี้ให้เห็นว่า การเกิดภาวะพหุสัณฐานทางพันธุกรรมของยีน GC (rs7041 (A>C)) มีความสัมพันธ์อย่างมีนัยสำคัญกับความเสี่ยงที่เพิ่มขึ้นต่อการเกิดภาวะออทิซึมสเปกตรัมและความรุนแรงของอาการออทิซึมสเปกตรัมด้วย โดยเฉพาะอย่างยิ่งบุคคลที่มีการขาดระดับวิตามินดีร่วมด้วย นอกจากนี้ผลศึกษาพบว่าไอโซฟอร์มของ GC1s และ GC1s-GC1s ฟีโนไทป์มีความสัมพันธ์อย่างมีนัยสำคัญกับความเสี่ยงต่อการเกิดภาวะออทิซึมสเปกตรัมตลอดจนความรุนแรงของอาการออทิซึมสเปกตรัม โดยสรุปการศึกษาวิจัยในครั้งนี้ชี้ให้เห็นว่า การเกิดภาวะพหุสัณฐานทางพันธุกรรมของยีน GC (rs7041 (A>C)) และไอโซฟอร์ม GC1s อาจเป็นตัวบ่งชี้ทางพันธุกรรมที่สามารถช่วยในการประเมินความเสี่ยงต่อการเกิดภาวะออทิซึมสเปกตรัมและความรุนแรงของอาการออทิซึมสเปกตรัมในเด็กไทยได้ในอนาคต อย่างไรก็ตามการศึกษาในอนาคตควรศึกษาในกลุ่มประชากรที่ใหญ่ขึ้นเพื่อยืนยันผลการศึกษาวิจัยครั้งนี้

Development And Biological Evaluation Of Selective Small-Molecule Inhibitors Of The Human Cytochrome P450 1b1, Austin Hachey

Theses and Dissertations--Chemistry

The human cytochrome P450 1B1 (CYP1B1) is an emerging target for small- molecule therapeutics. Several solid tumors overexpress CYP1B1 to the degree that it has been referred to as a universal tumor antigen. Conversely, its expression is low in healthy tissues. CYP1B1 may drive tumorigenesis through promoting the formation of reactive toxins from environmental pollutants or from endogenous hormone substrates. Additionally, the expression of CYP1B1 in tumors is associated with resistance to several common chemotherapies and with poor prognoses in cancer patients. However, inhibiting CYP1B1 with small molecules has been demonstrated in cellular and murine model systems to reverse this …

Characterization Of Parp1-Dependent Poly-Adp-Ribosylation Of Sprtn, Quincee Simonson

Electronic Theses and Dissertations

DNA-protein crosslinks (DPCs) are a type of DNA lesion that form when proteins become covalently linked to DNA. It is estimated that replicating cells experience approximately 6,000 DPCs per day per genome during exponential growth (Ruggiano & Ramadan, 2021). If left unrepaired, DPCs can be lethal to cells. For this reason, cells have evolved multiple pathways to repair or bypass DPCs to survive. One such pathway involves SPRTN, a nuclear metalloprotease that plays a key role in the repair of DPCs through direct proteolysis (Lopez-Mosqueda et al., 2016; Vaz et al., 2016). Once SPRTN degrades the bulky protein component of …

Modulatory Effects Of Deacetylated Sialic Acids (A Sugar Residue) In Nk-Mediated Cytotoxicity And Targeted Therapy By Receptor Tyrosine Kinase Inhibitors, Mathias Tawiah Anim

Electronic Theses and Dissertations

The complex nature of the biology of cancer is still an unraveling science, yielding several biomarkers that have served as molecular targets for detection and treatment of the disease. How sugars, glycans, play a role has remained relatively uninvestigated. Sialic acid (Sia), a sugar residue on the surface of cells, has been identified as a hallmark of cancer and its progression. Sialic acid can be highly functionalized, but we became interested in acetylated Sias. This functional group is modulated by Sialate O- acetylesterase (encoded by the gene SIAE) and Sialate O-acetyltransferase (encoded by CASD1), enzymes that play a crucial role …

Approaches To Avoid Proteolysis During Protein Expression And Purification, Gary T. Henehan, Barry J. Ryan, Gemma K. Kinsella

Books/Book Chapters/ Proceedings

All cells contain proteases, which hydrolyze the peptide bonds between amino acids of a protein backbone. Typically, proteases are prevented from nonspecific proteolysis by regulation and by their physical separation into different subcellular compartments; however, this segregation is not retained during cell lysis, which is the initial step in any protein isolation procedure. Prevention of proteolysis during protein purification often takes the form of a two-pronged approach: first, inhibition of proteolysis in situ, followed by the early separation of the protease from the protein of interest via chromatographic purification. Protease inhibitors are routinely used to limit the effect of the …

Structural And Spectroscopic Study Of New Copper(Ii) And Zinc(Ii) Complexes Of Coumarin Oxyacetate Ligands And Determination Of Their Antimicrobial Activity, Muhammad Mujahid, Natasha Trendafilova, Georgina Rosair, Kevin Kavanagh, Maureen Walsh, Bernadette Creaven, Ivelina Georgieva

Articles

Tackling antimicrobial resistance is of increasing concern in a post-pandemic world where overuse of antibiotics has increased the threat of another pandemic caused by antimicrobial-resistant pathogens. Derivatives of coumarins, a naturally occurring bioactive compound, and its metal complexes have proven therapeutic potential as antimicrobial agents and in this study a series of copper(II) and zinc(II) complexes of coumarin oxyacetate ligands were synthesised and characterised by spectroscopic techniques (IR, 1H, 13C NMR, UV-Vis) and by X-ray crystallography for two of the zinc complexes. The experimental spectroscopic data were then interpreted on the basis of molecular structure modelling and subsequent spectra simulation …

Identification Of Novel Biosynthetic Gene Clusters Encoding For Polyketide/Nrps-Producing Chemotherapeutic Compounds From Marine-Derived Streptomyces Hygroscopicus From A Marine Sanctuary, Hannah Ruth Flaherty

Honors Theses and Capstones

Nearly one out of six deaths in 2020, around ten million people, were caused by cancer, making it a leading cause of death worldwide (WHO, 2022). This major public health issue, in addition to the rise of multidrug-resistant (MDR) pathogens, provides a high demand for the discovery of new pharmaceutical drugs to be used clinically to treat these conditions. The Streptomyces genus accounts to produce 39% of all microbial metabolites currently approved for human health, indicating its potential as an important species to study for antimicrobial and anticancer agents. The long linear genome of Streptomyces contains specialized sequences known as …

Structural Files For The Etr1 Ethylene-Receptor Dimer Based On Computational Modeling, Beenish J. Azhar, Safdar Abbas, Sitwat Aman, Maria V. Yamburenko, Wei Chen, Lena Muller, Buket Uzun, David A. Jewell, Jian Dong, Samina N. Shakeel, Georg Groth, Brad M. Binder, Gevorg Grigoryan, G. Eric Schaller

Dartmouth Scholarship

Structural models for the ETR1 homodimer were generated with AlphaFold-Multimer. Coppers were modeled under two potential coordinations involving Cys65 and His69 of the ETR1 homodimer, one in which the two coppers are bound independently and do not share an interaction with each other, and another where they are closely bonded.

See the following publication for details: Azhar, B.J., Abbas, S., Aman, S., Yamburenko, M.V., Chen, W., Müller, L., Uzun, B., Jewell, D.A., Dong, J., Shakeel, S.N., Groth, G., Binder, B.M., Grigoryan, G., Schaller, G.E. (2023) Basis for high-affinity ethylene binding by the ethylene receptor ETR1 of Arabidopsis. Proc. Natl. Acad. …

Design Of Block Copolymer With Tunable Hydrophobic/Hydrophilic/Fluorophilic Interactions, Tatiane De Fatima Dutra

Theses, Dissertations and Culminating Projects

Block copolymers (BCP) with balanced interactions and their resultant bulk-phase self-assembly have become increasingly important in advancing nanotechnology, separation, and energy applications. However, a few reports have addressed the synthesis challenge and bulk-phase self-assembly of such triblock copolymers. This thesis presents a facile route for preparing triblock copolymer via controlled radical and organocatalytic ring-opening polymerization that allows precise control over the incorporation of individual moieties in resultant polymer, responsible for balanced hydrophilic, hydrophobic/lipophilic, and fluorophilic interactions. Synthesized polymer with suggested self-assembled 2D lamellar nanostructure exhibits high-temperature stability. The long-term goal of this work is to selectively use this polymer class …

A Computational Study Of The Copper-Catalyzed Trifluoromethylation Of Boronic Acids, Kevin Nyhuis

Theses, Dissertations and Culminating Projects

This work is a computational study of a reaction mechanism for the trifluoromethylation of boronic acids. Three steps of the proposed reaction mechanism are studied, •CF₃ addition to a copper catalyst center, base promoted transmetalation between copper and aryl boronic acid, and bond forming reductive elimination in which the CF₃ and aryl substituent form a bond. Limited information is known about this mechanism. This study uses computational methods to attempt to elucidate the mechanism and provide the groundwork for potential improvement. Quantum chemical methods in conjunction with tight-binding based conformational sampling methods are used to investigate the possible …

Investigating The Roles Of Active Site Residues K59, K119 And E168 In M. Tuberculosis Indole-3-Glycerol Phosphate Synthase, Maryum M. Bhatti

Theses, Dissertations and Culminating Projects

Tuberculosis (TB) is a disease that is caused by a bacteria called Mycobacterium tuberculosis and primarily attacks the lungs but can spread to other areas of the body as well. TB can develop resistance to drugs that may be used to cure the disease. Multidrug resistant TB is especially a growing issue as it does not respond to the two most powerful anti-TB drugs, isoniazid and rifampicin. For this reason, finding new ways to target TB are critically needed. One possible way to do this is to target the enzymes in the tryptophan biosynthetic pathway of M. tuberculosis. Studies have …

Presumptive Hepatogenous Photosensitization In Beef Cattle Winter Grazing A Cover Crop Containing Brassica Spp. Turnips, Matthew M. Hille, Scott A. Fritz, Breanna C. Brown

School of Veterinary and Biomedical Sciences: Faculty Publications

Over a period of ~2 wk, 5 adult beef cows developed severe necrotizing skin lesions on the face and neck shortly after being moved to a field with a cover crop of Brassica spp. turnips. We describe here the clinical signs, hematology, and serum chemistry results, as well as gross and histopathologic findings, from this outbreak. We made a presumptive diagnosis of Brassica-associated liver disease (BALD) based on the similarities in the history and diagnostic findings observed with previously reported cases of BALD from elsewhere in the world. BALD has not been reported previously in cattle in North America, …

Arginine-178 Is An Essential Residue For Itpa Function, Nicholas E. Burgis, Caitlin April, Kandise Vanwormer

Chemistry and Biochemistry Faculty Publications

The inosine triphosphate pyrophosphatase (ITPA) enzyme plays a critical cellular role by removing noncanonical nucleoside triphosphates from nucleotide pools. One of the first pathological ITPA mutants identified is R178C (rs746930990), which causes a fatal infantile encephalopathy, termed developmental and epileptic encephalopathy 35 (DEE 35). The accumulation of noncanonical nucleotides such as inosine triphosphate (ITP), is suspected to affect RNA and/or interfere with normal nucleotide function, leading to development of DEE 35. Molecular dynamics simulations have shown that the very rare R178C mutation does not significantly perturb the overall structure of the protein, but results in a high level of structural …

Role Of Grb2 Intracellular Localization In Progesterone Receptor Positive Breast Cancer, Nattamolphan Wittayavimol

Chulalongkorn University Theses and Dissertations (Chula ETD)

Progesterone receptor (PR) extranuclear signaling mediates mainly through PR polyproline domain (PPD) interaction with SH3 domain of cytoplasmic signaling molecules. PR-PPD interfered with Grb2-SOS binding through SH3 interaction resulting in decreased cell proliferation and correlates with a good prognosis in PR positive breast cancer. Grb2 is a key adaptor molecule and expressed in both nucleus and cytoplasm. We hypothesized that change in Grb2 localization alters PR transcription resulting in better clinical outcomes in PR positive breast cancer. BT-474 breast cancer cells expressing inducible Grb2-SV402x (nuclear Grb2, nuGrb2) or Grb2-MYR (membrane Grb2, memGrb2) were constructed. MemGrb2-BT-474 showed higher levels of PR …

Roles Of Progesterone Signaling On Dna Repair And Cell Survival In Ovarian Cancer Cells, Pattarasiri Rangsrikitphoti

Chulalongkorn University Theses and Dissertations (Chula ETD)

Every year over 300,000 women worldwide are diagnosed with ovarian cancer and half of these patients die from this disease. The symptoms of ovarian cancer are very general and often confused with other common female diseases making ovarian cancer a challenging disease to diagnose and treat. Platinum-based chemotherapy, including cisplatin, stands as the first-line treatment for ovarian cancer. However, chemotherapy resistance remains a continuing problem, contributing to a high mortality rate. Progesterone receptor (PR) signaling has been implicated in various aspects of ovarian cancer biology. Clinical studies show a positive correlation between PR expression, improved patient survival and cisplatin response, …

Cisplatin - Loaded Calcium Citrate Nanoparticlesfor Inhibition Of Lung Cancer Cell Growthand Quantum Mechanical Study Of Cisplatin And Citrate, Lipika Oopkaew

Chulalongkorn University Theses and Dissertations (Chula ETD)

The International Organization for Research on Cancer (International Agency for Research on Cancer (IARC) issued a statement saying lung cancer is a cancer with high incidence rates of new cases and deaths. Although there are current therapeutic approaches such as surgery, radiation therapy, and chemotherapy. However, these treatments exhibit ineffectiveness; the main limitation is severe side effects to normal cells or non-target organs. To address this challenge, the development of targeted therapy by nanoparticle-based drug delivery system is applied to increase drug stability and control the specificity to cancer cells with target-specific proteins that play an important role in intracellular …

Protein Extraction And Purification By Differential Solubilization, Barry J. Ryan, Gemma K. Kinsella, Gary T. Henehan

Books/Book Chapters/ Proceedings

The preparation of purified soluble proteins for biochemical studies is essential and the solubility of a protein of interest in various media is central to this process. Selectively altering the solubility of a protein is a rapid and economical step in protein purification and is based on exploiting the inherent physicochemical properties of a polypeptide. Precipitation of proteins, released from cells upon lysis, is often used to concentrate a protein of interest before further purification steps (e.g., ion exchange chromatography, size exclusion chromatography etc).

Recombinant proteins may be expressed in host cells as insoluble inclusion bodies due to various influences …

Apobec3 Regulation By Thyroid Hormone, Michelle Santiago

All Graduate Theses, Dissertations, and Other Capstone Projects

Thyroid hormone (TH) is crucial for many biological processes, including the development of the auditory system. Appropriate thyroid hormone signaling is important for the development of the cochlea, leading to the successful onset of hearing. More specifically, TH influences the timing of remodeling of the greater epithelial ridge (GER), a transient cochlear structure that secretes proteins that contribute to the formation of the tectorial membrane. Developmental hypothyroidism results in delayed GER regression, whereas excess TH results in premature remodeling. Both conditions result in deafness. However, it is unknown how TH mediates GER remodeling. Expression profiling identified APOBEC3 (A3) as a …

The Molecular Mechanisms Of Ifn-Γ Promoted Necroptosis In Macrophages, Meghan R. Vogt

Biotechnology Theses

Necroptosis, a form of programmed lytic cell death, has emerged as a driving factor in the pathogenesis of acute lung injury. One specific inflammatory mediator that is of interest is interferon-γ (IFN-γ). Our laboratory has reported that IFN-γ is the most potent enhancer of necroptosis in primary lung epithelial cells and macrophages by upregulating MLKL expression. How IFN-γ enhances necroptosis and MLKL upregulation is currently unknown. In this research, we utilized multiple approaches to study the potential molecular mechanisms of IFN-γ promoted necroptosis in macrophages. We found that MLKL and ZBP1 are significantly upregulated by IFN-γ through an unknown pathway …

Investigating The Relationship Between Metabolic Reprogramming And Peripheral Cd4+ T-Cell Inflammation In Human Type 2 Diabetes Pathogenesis, Gabriella Kalantar

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Chronic, low-grade systemic inflammation rises in obesity and promotes type 2 diabetes (T2D). Circulating immune cells are key indicators of obesity and T2D pathogenesis. T cells outnumber monocytes, in blood, suggesting that T cells might fuel peripheral inflammation in obesity/T2D. Our lab’s work supports this idea by identification of a Th17 cytokine profile in T2D from T-cell stimulated peripheral blood mononuclear cells. Work described herein further supported this work by demonstrating that T cells dominate peripheral inflammation over monocytes across the spectrum of obesity and glycemic control. Our lab has also recently shown that inflammation changes during prediabetes (preT2D), identified …

Developing A Biocatalytic Toolbox To Aid In Understanding Nucleoside Antibiotics, Jasmine Brianna Woods

Theses and Dissertations--Pharmacy

Antibiotic resistance happens when bacteria develop the ability to survive medications that normally terminate them. Instead, these super germs are able to survive in the body and produce a community of antibiotic resistance germs which can cause human fatalities. It is important to discover and develop new compounds and molecules that will improve this clinical obstacle. This research focused on analyzing the biosynthesis that incorporates distinctive chemical characteristic of various nucleoside antibiotics, ß-hydroxy amino acids and α-methyl-amino acids. ß-hydroxy amino acids and α-methyl-amino acids are considered an important class of industrially useful compounds, particularly for pharmaceutical development, and are found …

Impact Of Sample Conditions On Dna Phosphodiester Backbone Bi/Bii Conformational Equilibrium Dynamics, Autumn C. Pilarski

Graduate Theses/Dissertations

DNA damage, such as single base lesions and mismatches, is highly prevalent within cells. If these DNA damage events are not repaired, they could lead to mutations and thus disease and cancer. Intricate repair mechanisms are in place to fix these damage events, one such being Base Excision Repair (BER) and associated enzyme: Thymine DNA Glycosylase (TDG). The first step of this repair process, recognition of the lesion by TDG, is not well understood. The following thesis presents results to better understand the fundamental biophysical question of how a DNA lesion within a mismatch context is recognized in a million …

Investigating Mirna Regulation Of The Human Apobec3 Enzymes, William Dietrich

All Graduate Theses, Dissertations, and Other Capstone Projects

The human apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3, A3) are a family of proteins consisting of seven enzymes, A3A, B, C, D, F, G and H, which function as cytosine deaminases. The enzymes’ purpose in the cell is to mutate viral DNA during infection hindering or stopping replication of viruses such as human papillomavirus, herpes simplex virus, and HIV-1. Several of the A3 enzymes have also been implicated in contributing to cancers such as head and neck and breast cancers by mutating cellular genomic DNA, making the ability to control A3 expression an attractive target for cancer …

Novel Amino Acids Dictate Differences In Sivmac239 And Hiv-2 Rod9 Vpx Cellular Localization, Hunter D. Mayhew

All Graduate Theses, Dissertations, and Other Capstone Projects

Vpx is a protein encoded by Human Immunodeficiency Virus Type 2 (HIV-2) and specific Simian Immunodeficiency Viruses (SIVs) that is essential for successful infection of non-dividing myeloid cells. Vpx facilitates viral replication by trafficking the viral genome into the nucleus of infected cells and targeting the primarily nuclear innate immune protein SAMHD1 for proteasomal degradation. Considering that these activities occur at the nucleus, we hypothesized that Vpx nuclear localization would be tightly correlated with these functions. To assess this, site directed mutagenesis in combination with confocal microscopy or Western Blotting analyses were utilized to evaluate the determinants of nuclear accumulation …

Investigation Of Mechanical Regulation On Stat3 Activity And Mmp Production, Jaxson R. Libby

Honors Theses and Capstones

Transcription factor, STAT3, is inappropriately expressed in cancer cells, and has contrasting activation in 2D versus 3D microenvironments. 2D plates are often used for drug screening and do not always recapitulate in vivo responses. To combat inaccurate 2D drug studies, a 3D hydrogel was created to support the growth of cancer cells into a tumor-like environment. The hydrogel consists of a biocompatible dextran homopolysaccharide, cell adhesion RGD sequences, and crosslinker MMP labile peptides. A pH dependent reaction couples the RGD sequences to dextran then the polymers are crosslinked into a gel. Crosslinking is accomplished using terminal cysteine peptide sequences, allowing …