Biochemistry, Biophysics, and Structural Biology Commons^™

A Novel Transmembrane Ligand Inhibits T Cell Receptor Activation, Yujie Ye

Doctoral Dissertations

T lymphocytes (T cells) play essential roles in the adaptive immune system. Each mature T cell expresses one type of functional T cell receptor (TCR). The TCR recognizes antigens bound to the major histocompatibility complex (MHC) in antigen presenting cells. The resulting stimulation signal crosses the transmembrane domain of TCR and initiates downstream signaling cascades. The human immune system relies on TCRs to recognize a variety of pathogens. Normally, TCR can distinguish the self-antigens from pathogenic antigens. However, dysfunction or aberrant expression of TCRs causes different inflammatory and autoimmune diseases, which afflict millions of people annually (Chapter I). Current treatments …

Investigating The Role Of Dullard And Tmem-188 In Lipid Droplet Biogenesis In Mammalian Cells, Mia Kaitlin Buono

Chancellor’s Honors Program Projects

No abstract provided.

Calmodulin Like 38 Is Required For Autophagy Of Hypoxia-Induced Cytoplasmic Rna Granules In Arabidopsis Thaliana, Sterling Field

Doctoral Dissertations

In response to the energy crisis resulting from submergence stress and hypoxia, the model plant Arabidopsis thaliana limits non-essential mRNA translation, and accumulates cytosolic stress granules. Stress granules are phase-separated mRNA-protein particles that partition transcripts for various fates: storage, degradation, or return to translation after stress alleviation. Another response by the plant cell to low oxygen stress is the induction of the turnover pathway autophagy. Stress granule regulation by autophagy occurs by a ‘granulophagy’ pathway in yeast and mammalian systems through which parts or whole stress granules are degraded. Whether this occurs in plants has not been investigated.

A connection …

Erecta Family Genes Regulate The Shoot Apical Meristem And Organ Formation, Daniel A. Degennaro

Doctoral Dissertations

Plants are sessile and must adjust their organ growth to their environments. A reservoir of stem cells in the shoot apical meristem (SAM) supplies cells for differentiation into organs. The SAM must balance organ production with stem cell maintenance. The ERECTA family (ERfs) encodes the leucine-rich repeat receptor-like kinases ERECTA (ER), ERECTA-LIKE 1 (ERL1), and ERL2. ERf signaling regulates organ initiation and stem cell maintenance. Results presented in this work include the following:

1) WUSCHEL (WUS) and CLAVATA3 (CLV3) make up a negative feedback loop to maintain SAM size. WUS and CLV3 expression localization is critical for …

The Histone Variant H2av Regulates Stress Responses And Tissue Development Through Interactions With Chromatin Insulator Proteins In Drosophila Melanogaster, James Ryan Simmons

Doctoral Dissertations

The ability of a cell to sense and respond to various forms of stress is essential to maintain integrity of the genome. Numerous pathways have been implicated in cellular responses to environmental and genotoxic stresses, often involving proteins and complexes that bind DNA directly to orchestrate changes in transcription and genome organization. Chromatin insulators describe a class of protein complex that bind specific sequences in the genome and work through two classically described functions: to restrict communication between enhancers and promoters through physical separation into different genomic domains and to prevent the spread of heterochromatin into euchromatic regions of the …

Iojap: Morphological And Physiological Phenotype Characterization In Arabidopsis, Thomas Jay Payne

Doctoral Dissertations

IOJAP protein is found in all organisms that contain a ribosome of bacterial origin. The majority of studies suggest that IOJAP plays a role in translation, although this has yet to be thoroughly investigated in plants. Using Arabidopsis thaliana, an extensive phenotype characterization of iojap mutants was performed. Many processes of plant growth were slightly impaired at optimal temperature (22˚C) but became severely hindered at low temperature (12˚C and 4˚C). These cold temperature defects manifested in an overall reduction of plant growth as well as variegation, chlorosis, leaf hyponasty, as well as reduced maximum quantum yield (F_v/F …

Investigating The Effects Of Excitotoxic Stimuli On The Suprachiasmatic Nucleus, Rachel A. Brandes

Chancellor’s Honors Program Projects

No abstract provided.

Investigation For Novel Anti-Apoptotic Factors In The Neurons Of Drosophila Melanogaster, Haylie Rachel Lam

Chancellor’s Honors Program Projects

No abstract provided.

Constitutive Expression Of Thioglucoside Glucohydrolase 1 (Tgg1) Decreases Intercellular Trafficking In Arabidopsis Thaliana, Alessandro Francesco Sarno

EURēCA: Exhibition of Undergraduate Research and Creative Achievement

Plasmodesmata (PD) are pores that traverse plant cell walls, providing a route for intercellular trafficking of essential metabolites, nutrients, and signaling molecules between adjacent plant cells, thereby aiding communication. The increased size exclusion limit 2 (ise2) mutant of Arabidopsis thaliana has an increased abundance of branched PD, as well as a greater flux of intercellular trafficking. A search for proteins that interact with ISE2 identified THIOGLUCOSIDE GLUCOHYDROLASE 2 (a myrosinase). A. thaliana also encodes a second, closely-related myrosinase, TGG1. Myrosinases are enzymes that catalyze the hydrolysis of glucosinolates, a type of secondary metabolite that are amino acid derivatives. The breakdown …

Myosin Xi-I Works In Tandem With A Microtubule-Associated Mechanism To Position The Nucleus In Arabidopsis Root Hairs, Ian Andrew Windham

Chancellor’s Honors Program Projects

No abstract provided.

Biophysical Studies Of Cell Division Protein Localization Mechanisms In Escherichia Coli, Matthew Wayne Bailey

Doctoral Dissertations

How nanometer-scale proteins position accurately within micron-scale bacteria has intrigued both biologists and physicists alike. A critical process requiring precise protein localization is cell division. In most bacteria, cell division starts with the self-assembly of the FtsZ proteins into filaments that form a ring-like structure encircling the cell at its middle, the Z-ring. The Z-ring is a scaffold for additional proteins that synthesize the lateral cell wall which separates the two daughter cells. If division planes are misplaced relative to bacterial chromosomes, also called nucleoids, daughter cells with incomplete genetic material can be produced. In Escherichia coli, research carried out …

Calmodulin-Like Protein 38: A Component Of Ribonucleoprotein Particles During Hypoxic Stress Responses In Arabidopsis, Ansul Lokdarshi

Doctoral Dissertations

Waterlogging stress leads to a crisis in energy metabolism and the accumulation of toxic metabolites due to the hypoxic and/or anoxic environment associated with this condition. To respond and adapt to this situation, higher plants employ an integrated genetic program that leads to the induction of anaerobic response polypeptide genes that encode metabolic and signaling proteins involved in altering metabolic flow and other adaptive responses. The study presented here shows that the Arabidopsis thaliana calmodulin-like protein CML38 is calcium sensor protein that serves as a member of the core anaerobic response gene family and is involved in modulating the survival …

The Characterization Of Amyloid Fibrils And Novel Synthetic Heparin-Binding Peptides Binding To Cell Surfaces, Nicole Marie Hackenbrack

Chancellor’s Honors Program Projects

No abstract provided.

Characterization Of The Role Of Alpha-Arylphorin In The Heliothis Virescens Midgut Response To Cry1ac Toxin From Bacillus Thuringiensis, Jerreme Jamael Jackson

Doctoral Dissertations

Homeostasis of the intestinal epithelium in Heliothis virescens is mediated by the proliferation and differentiation of multipotent intestinal stem cells (ISCs) that lie adjacent to the basal lamina. In response to extrinsic and intrinsic signals, ISC proliferation and differentiation promotes epithelial growth and regeneration following the loss of integrity. We tested the in vivo effects of the ISC mitogen, a [alpha]-arylphorin, on ISC proliferation and the morphological changes of the midgut during larval development. Additionally, we examined how these changes affected the intestinal epithelium response to Cry1Ac toxin from Bacillus thuringiensis. Histological and in vitro evidence supported two distinct …

The Role Of Nag-1 In Tumorigenesis, Kyung-Won Min

Doctoral Dissertations

This dissertation explores the nature of a divergent member of the Transforming Growth Factor-β [beta] superfamily, the non-steroidal anti-inflammatory drugs activated gene (NAG-1), as it relates to its regulation and biological activity in cancer context. Our lab has extensively studied on the molecular mechanism by which phytochemicals and NSAIDs induce apoptosis correlation with NAG-1 expression in human colorectal cancer (CRC) cells. Significant data from in vitro studies suggest that NAG-1 has an anti-tumorigenic activity which elicits apoptosis in a cyclooxygenase (COX)-independent manner in CRC cells. Indeed, NAG-1 transgenic mice developed less aberrant polyp foci (APC) compared to those of control …

Examining The Functional Consequences Of The Flexibility Of Aminoglycoside Phosphotransferase (3’)-Iiia, Katelyn Dawn Rosendall

Masters Theses

The use of aminoglycoside antibiotics began in 1940 with the discovery of streptomycin. The overuse and misuse of antibiotics has resulted in prevalent cases of antibiotic resistance. The most common source of aminoglycoside resistance is the presence of enzymes that covalently modify the antibiotics at specific locations. One such enzyme, APH(3′)-IIIa [the aminoglycoside phosphotransferase three prime three a] conveys resistance by transferring the γ-phosphate [gamma phosphate] from ATP [adenosine triphosphate] onto the 3′ [three prime] carbon of the aminoglycoside antibiotic sugar ring. APH(3′)-IIIa has been shown to be flexible in solution and this flexibility is proposed to be responsible for …

Chromatin Insulators: Master Regulators Of The Eukaryotic Genome, Todd Andrew Schoborg

Doctoral Dissertations

Proper organization of the chromatin fiber within the three dimensional space of the eukaryotic nucleus relies on a number of DNA elements and their interacting proteins whose structural and functional consequences exert significant influence on genome behavior. Chromatin insulators are one such example, where it is thought that these elements assist in the formation of higher order chromatin loop structures by mediating long-range contacts between distant sites scattered throughout the genome. Such looping serves a dual role, helping to satisfy both the physical constraints needed to package the linear DNA polymer within the small volume of the nucleus while simultaneously …

Characterization Of A Glycosyphosphatidylinositol Anchor Transamidase In Arabidopsis Thaliana And The Function Of Gpi Anchored Proteins In Stomatal Development, Mark Gerald Ronald Bundy

Masters Theses

In plants stomata play a vital role for survival by allowing the gas exchange of CO₂ [carbon dioxide] and water vapor to occur. A stoma is a central pore flanked by two kidney shaped guard cells and in wild type there is at least one pavement cell between each stoma. The ERECTA (ER) gene family consisting of ER, ERL1, ERL2 is involved in regulation of stomata development, where a triple mutant of er erl1 erl2 displays an increased stomata index and clusters of stomata that disobey the one cell spacing rule. To better understand the pathway of stomata development, …

Role Of Retinoids In The Regulation Of Hepatic Glucose And Lipid Metabolism, Rui Li

Doctoral Dissertations

The liver plays an important role in controlling glucose and lipid homeostasis. Metabolic abnormalities such as obesity and type 2 diabetes are often associated with profound changes in the expression of genes involved in hepatic glucose and lipid metabolism. Dietary nutrients provide us with macronutrients for energy and micronutrients for maintenance of general health. However, the effects of individual micronutrients on the development of metabolic diseases are unknown. Sterol regulatory element binding protein-1c (SREBP-1c) is the master regulator of fatty acid synthesis, and glucokinase (GK) is the key enzyme in glucose metabolism. Based on the preliminary results from our laboratory …

Experimental And Computational Analysis Of Chloroplast Transit Peptide Domain Architecture And Function, Prakitchai Chotewutmontri

Doctoral Dissertations

The Majority of chloroplast proteins are nuclear-encoded and utilize an N-terminal transit peptide (TP) to target into chloroplasts via the general import pathway. Bioinformatic and proteomic analyses provide thousands of predicted TPs, which show low sequence similarity. How the common chloroplast translocon components recognize these diverse TPs is not well understood. Previous results support either sequence- or physicochemical-specific recognitions. To further address this question, a reverse sequence approach was utilized such that the reverse TP contains the same amino acid composition as wild-type TP but lack similar sequence motifs. Using both native and reverse TPs of the two well-studied precursors, …

Development And Application Of Mass Spectrometry-Based Proteomics To Generate And Navigate The Proteomes Of The Genus Populus, Paul Edward Abraham

Doctoral Dissertations

Historically, there has been tremendous synergy between biology and analytical technology, such that one drives the development of the other. Over the past two decades, their interrelatedness has catalyzed entirely new experimental approaches and unlocked new types of biological questions, as exemplified by the advancements of the field of mass spectrometry (MS)-based proteomics. MS-based proteomics, which provides a more complete measurement of all the proteins in a cell, has revolutionized a variety of scientific fields, ranging from characterizing proteins expressed by a microorganism to tracking cancer-related biomarkers. Though MS technology has advanced significantly, the analysis of complicated proteomes, such as …

Phosphorylation Regulates Myosin Driven Organelle Movements, Peter Andrew Duden

EURēCA: Exhibition of Undergraduate Research and Creative Achievement

Cytoplasmic streaming in plant cells is the continuous flow of cytoplasm and organelles throughout the cell, with the first observation of cytoplasmic streaming being publicized in 1774. However, the mechanism of cytoplasmic streaming remained unclear until components of the cytoskeleton were researched. Research now supports that the motive force generating cytoplasmic streaming is the interaction of myosin XI motor proteins with organelles while sliding along actin filaments. From this, a key topic of interest is how myosin driven organelle movement is regulated. Our research focuses on whether phosphorylation affects the regulation of myosin XI motor proteins. Specifically, the goal of …

Elucidating The Effect Of Silver On Ethylene Signaling In Arabidopsis Thaliana, Brittany Kathleen Mcdaniel

Masters Theses

Ethylene, a gaseous plant hormone, is involved in numerous plant developmental processes such as seed germination, senescence, and fruit ripening. In Arabidopsis thaliana, ethylene is perceived by a family of five membrane-bound receptors, which upon binding ethylene trigger downstream effects. At the receptor level, it is known that the coordination of a copper ion is necessary for ethylene to bind, resulting in a conformational change of the receptor and the initiation of the ethylene signal transduction pathway. Interestingly, silver ions are also able to support binding of ethylene but ethylene responses are blocked in the presence of silver. When …

Suppression Of Chronically Induced Breast Carcinogenesis And Role Of Mesenchymal Stem-Like Cells, Kusum Rathore

Doctoral Dissertations

Sporadic breast cancers are mainly attributable to long-term exposure to environmental factors, via a multi-year, multi-step, and multi-path process of tumorigenesis involving cumulative genetic and epigenetic alterations in the chronic carcinogenesis of breast cells from a non-cancerous stage to precancerous and cancerous stages. Epidemiologic and experimental studies have suggested that various dietary compounds like green tea and grape seed may be used as preventive agents for breast cancer control. In this research, I have developed a cellular model that mimics breast cell carcinogenesis chronically induced by cumulative exposures to low doses of environmental carcinogens. I used the chronic carcinogenesis model …

Novel Constitutively Active Point Mutations In The Nh2 Domain Of Cxcr2 Capture The Receptor In Different Activation States, Giljun Park

Doctoral Dissertations

Chemokines are structurally and functionally related 8-10 kDa proteins defined by four conserved cysteine residues. They consist of a superfamily of proinflammatory mediators that promote the recruitment of various kinds of leukocytes and other cell types through binding to their respective chemokine receptor, a member of the GPCR family. Abnormal control of this system results in various diseases including tumorigenesis and cancer metastasis. Deregulation can occur when constitutively active mutant (CAM) chemokine receptors are locked in the “on” position. This can lead to cellular transformation/tumorigenesis. A viral CAM receptor, ORF74, that can cause tumors in humans, also has homology to …

Study Of The Structure And Function Of Cxc Chemokine Receptor 2, Hae Ryong Kwon

Masters Theses

It has been shown that the amino terminus and second extracellular loop (EC2) of CXCR2 are crucial for ligand binding and receptor activation. The lack of an ionic lock motif in the third intracellular loop of CXCR2 focuses an investigation of the mechanism by which these two extracellular regions contribute to receptor recognition and activation.

The first objective of this investigation was to predict the structure of CXCR2 based on known structures of crystallized GPCRs. Rhodopsin, β2-adrenergic receptor, CXCR4 were used for homology modeling of CXCR2 structure. Highly conserved motifs found in sequence alignments of the template GPCRs were helpful …

Characterizing The Role Of Dna Repair Proteins In Telomere Length Regulation And Maintenance: Fanconi Anemia Complementation Group C Protein And 8-Oxoguanine Dna Glycosylase, David Beomjin Rhee

Doctoral Dissertations

Telomeres are the chromosome end structures consisting of telomere-associated proteins and short tandem repeat sequences, TTAGGG, in humans and mice. Telomeres prevent chromosome termini from being recognized as broken DNA ends. The structural integrity of DNA including telomeres is constantly threatened by a variety of DNA damaging agents on a daily basis. To counteract the constant threats from DNA damage, organisms have developed a number of DNA repair pathways to ensure that the integrity of genome remains intact. A number of DNA repair proteins localize to telomeres and contribute to telomere maintenance; however, it is still unclear as to what …

Functional Analysis Of Chromodomain Helicase Dna Binding Protein 2(Chd2) Mediated Genomic Stability, Sangeetha Rajagopalan

Doctoral Dissertations

Histone modifying enzymes and chromatin remodeling complexes play an important regulatory role in chromatin dynamics that dictate the interaction of regulatory factors involved in processes such as DNA replication, recombination, repair and transcription, with DNA template. The CHD (Chromodomain Helicase DNA Binding Protein) family of proteins is known to be involved in the regulation of gene expression, recombination and chromatin remodeling via their chromatin specific interactions and activities. Phenotypic analysis of the Chd2 mutant mouse model developed by our laboratory indicates that the Chd2 protein plays a critical role in tumor suppression as the heterozygous mutant mice develop spontaneous lymphomas. …

Reverse Genetic And Cell Biological Approaches To The Study Of Developmental Functions Of Class Xi Myosin In Arabidopsis Thaliana, Eunsook Park

Doctoral Dissertations

Myosin proteins function as molecular motors that drive the ATP-dependent movement of cellular components along actin filaments. Vascular plants encode two different types of myosin, referred to as class VIII and class XI. Although class XI myosins have been suggested to function in organelle movement and cytoplasmic streaming, little is known about their cellular function in detail.

The Arabidopsis genome encodes 13 class XI myosin genes. The reasons for the relatively large number of myosin XI isoforms present within a single plant species are unknown. To investigate the function of these gene products in the cell, we determined the spatial …

Ppar Agonists Down-Regulate The Expression Of Atp10c Mrna During Adipogenesis, A Peretich, Maria Cekanova Ms, Rndr, Phd, S Hurst, Sj Baek, Madhu Dahr

Faculty Publications and Other Works -- Biochemistry, Cellular and Molecular Biology

No abstract provided.