Life Sciences 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 …

What I Talk About When I Talk About Integration Of Single-Cell Data, Yang Xu

Doctoral Dissertations

Over the past decade, single-cell technologies evolved from profiling hundreds of cells to millions of cells, and emerged from a single modality of data to cover multiple views at single-cell resolution, including genome, epigenome, transcriptome, and so on. With advance of these single-cell technologies, the booming of multimodal single-cell data creates a valuable resource for us to understand cellular heterogeneity and molecular mechanism at a comprehensive level. However, the large-scale multimodal single-cell data also presents a huge computational challenge for insightful integrative analysis. Here, I will lay out problems in data integration that single-cell research community is interested in and …

Metabolism In The Colonocyte: Where Bacteria And Diet Meet, Bohye Park

Doctoral Dissertations

The host-microbiome interaction and the functions of microbial-derived metabolites, including butyrate, are important in colon health. Butyrate is the preferred energy source in colonocytes and has multiple physiological functions in the colon. A metabolic shift in colonocytes toward increased glucose utilization from butyrate oxidation is followed by several critical genetic modifications in cancerous colonocytes. Moreover, it has been suggested that the gut-microbiota composition is influenced by environmental factors, such as diets and the host's physiological status. Therefore, an understanding of the role of colonocyte metabolism toward impacting the host-microbiota commensal relationship would be an important step in understanding the functional …

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 …

The Role Of Cdc42 Regulation In Cell Growth Pattern And Timing, Julie Robinson

Doctoral Dissertations

In fission yeast, polarized cell growth stops during division and resumes after cell separation at the end that existed in the previous generation. It is unclear how growth occurs specifically at this end after cell division. Via a pedigree analysis of mutant cells which display a unique polarity phenotype, we show the existence of a memory of growth. This memory of growth exists at the pre-existing cell end, which grew in the previous generation, and facilitates growth at that end in the next generation. This memory of growth gives the pre-existing end some advantage in a competition for active Cdc42, …

Biofabricated Constructs Of Carbon-Based Nanoparticles With Mesenchymal Stem Cells For Orthopedic Repair, Steven D. Newby

Doctoral Dissertations

Breakthroughs in tissue engineering are moving at a rapid rate especially in the regenerative bone biofabrication. Technology growth in the field of additive manufacturing (AM) such 3D bioprinting which provides the ability to create biocompatible 3D construct on which a cell source could be seeded is an encouraging substitute to autologous grafts.

This present research aims to biofabricate a construct for bone tissue engineering using AM technology. The biocompatible material was chosen corresponding to bones extracellular matrix (ECM) composition, which demonstrates an inorganic and organic development phase: Poly (lactic-glycolic acid) was chosen as the polymeric matrix of the compound, due …

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.

A Mitotic Cue Triggers The Resumption Of Cell Growth After Division, Afton R. Russell

Chancellor’s Honors Program Projects

No abstract provided.

A Cell Cycle Cue Triggers Cell Growth Resumption After Division, Afton R. Russell

EURēCA: Exhibition of Undergraduate Research and Creative Achievement

The decoupling of the fundamental processes of cell division and growth is important for maintaining cell integrity. Through a chemical approach, we delayed the clock that controls when cells separate, uncoupling cell division and cell growth. This led to polarized cell growth before the cells completed separation. Using fluorescent markers to denote the cell’s stage in the cell cycle, we observed that only cells that were in mitosis exhibited this uncoupling. Previously it was thought that growth resumption occurred after completion of cell division, but this observation suggests that growth is triggered earlier, from a mitotic cue. This mitotic cue …

Investigating The Role Of The Rough Deal Protein In Spindle Assembly Complex Signaling, Ryan P. Mihealsick

Chancellor’s Honors Program Projects

No abstract provided.

Iteratively Improving Hi-C Experiments One Step At A Time, Rosela Golloshi, Jacob T. Sanders, Rachel Patton Mccord

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

The 3D organization of eukaryotic chromosomes affects key processes such as gene expression, DNA replication, cell division, and response to DNA damage. The genome-wide chromosome conformation capture (Hi-C) approach can characterize the landscape of 3D genome organization by measuring interaction frequencies between all genomic regions. Hi-C protocol improvements and rapid advances in DNA sequencing power have made Hi-C useful to study diverse biological systems, not only to elucidate the role of 3D genome structure in proper cellular function, but also to characterize genomic rearrangements, assemble new genomes, and consider chromatin interactions as potential biomarkers for diseases. Yet, the Hi-C protocol …

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 …

Using The Suprachiasmatic Nucleus As A Model System To Assess Tolerance And Withdrawal To Alcohol, Jonathan Houghton Lindsay

Doctoral Dissertations

Alcohol abuse induces many disorders including depression, metabolic syndrome, and sleep disturbances. The strong link between alcohol abuse and sleep problems, along with the close connection between sleep and circadian rhythms, led us to investigate ethanol’s effects on the circadian clock. Previous work has shown that acute ethanol blocks photic phase shifts in vivo and glutamatergic phase shifts in vitro. However, neural systems become tolerant to ethanol across different timeframes. Despite both ethanol tolerance and ethanol withdrawal syndrome being listed as criteria for developing alcohol use disorders, little is known about how ethanol tolerance and withdrawal induced hyperexcitability develop and …

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.

Identification Of A General Targeting Motif Guiding Interaction Between Nuclear-Encoded Plastid Precursors And The Translocon Of The Plastid Outer Membrane, Erika N. Sanders

Chancellor’s Honors Program Projects

No abstract provided.

Characterization Of The Chea2 Chemotaxis Operon In Azospirillum Brasilense, Erin Lutz

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 …

Expansion, Characterization, Differentiation, And Visualization Of Mc 3t3-E1 Preosteoblast Cells: An In Vitro Model To Study Bone Healing And Stem Cell-Mediated Regeneration, Jakob T. Samsel, Madhu Dhar, Austin Bow, Tom Masi

Chancellor’s Honors Program Projects

No abstract provided.

Brown And Beige Adipocytes: Effects Of Inflammation And Nutritional Intervention, Jiyoung Bae

Doctoral Dissertations

Recent findings of brown adipocytes and brown-like or beige adipocytes, capable of dissipating energy as heat, in adult humans have promised new hope for obesity treatment and prevention. Understanding of the regulation of brown and beige adipocytes will provide novel strategies to reach the goal. Pattern recognition receptors (PRR) are responsible for inflammation in adipose tissue, which leads to adipose dysfunction and obesity associated chronic diseases. It has been shown that PRR activation induces inflammation, leading to insulin resistance in white adipocytes and white adipose tissue (WAT). However, the roles of PRR activation in brown adipocytes and brown adipose tissue …

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.

Dominance Of Old End Growth Is Inherited In Fission Yeast, Julie Tia Rich

Chancellor’s Honors Program Projects

No abstract provided.

Reverse Genetics Approach To Examine Myosin Xi Functions In Pollen Tube Growth, Stephanie Lin Madison

Doctoral Dissertations

Pollen tube growth is an essential aspect of plant reproduction because it is the mechanism through which non-motile sperm cells are delivered to ovules thus allowing fertilization to occur. A pollen tube is a single cell that only grows at the tip, and this tip growth depends on actin filaments. Plants encode class VIII and class XI myosins as actin-based motor proteins, of which class XI myosins are required for cell expansion in vegetative tissues.

In Arabidopsis thaliana, 6 of 13 myosin XI genes are expressed in pollen: XIA, XIB, XIC, XID, XIE, and …

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 …

Understanding The Meiotic Roles Of Sisters Unbound In Drosophila Melanogaster, Badri Krishnan

Doctoral Dissertations

During meiosis, cohesin is required for sister chromatid cohesion and for formation of chromosome cores. Multiple processes including chromosome segregation, recombination and synaptonemal complex (SC) are dependent on cohesin. Cohesin complex consists of two SMC subunits- SMC1, SMC3 and two non-SMC subunits RAD21/REC8 in meiosis and SA. But in Drosophila, non-SMC subunits have not been shown to be required for cohesion. We have identified a gene sisters unbound, which along with previously identified ord and solo, form a group of three genes (sos) which do not have any sequence similarity to cohesins but performs functions …

Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Multiple sclerosis (MS) is a neurodegenerative disorder caused by a prolonged immune- mediated inflammatory response that targets myelin. Nearly all of the drugs approved for the treatment of MS are general immunosuppressants or only function in symptom management. The oral medication fingolimod, however, is reported to have direct therapeutic effects on cells of the central nervous system in addition to immunomodulatory functions. Fingolimod is known to interact with sphingosine-1-phosphate (S1P) receptors, and the most widely- accepted theory for its mechanism of action is functional antagonism of the receptor. This review examines significant neuromodulatory effects achieved by functional antagonism of the …