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Articles 1 - 21 of 21
Full-Text Articles in Molecular Biology
Determining The Roles Of The Oligomerization And C-Terminal Domains In Mutant P53 Gain-Of-Function Activities, George K. Annor
Determining The Roles Of The Oligomerization And C-Terminal Domains In Mutant P53 Gain-Of-Function Activities, George K. Annor
Dissertations, Theses, and Capstone Projects
The tumor suppressor p53 (TP53) gene is often mutated in cancer, with missense mutations found in the central DNA binding domain, and less often in the oligomerization domain (OD) and C-terminal domain (CTD). The OD and CTD have been found to be critical for the tumor suppressor functionality of wild-type p53 (wtp53). Specific missense mutations in the DNA binding domain have been found to confer new gain-of-function (GOF) activities. Mutations that destabilize tetramer formation, or deletion of key lysine residues within the CTD, downregulate the ability of wtp53 to transactivate (increase the rate of transcription of) its target …
Cdc6 Is Sequentially Regulated By Pp2a-Cdc55, Cdc14, And Sic1 For Origin Licensing In S. Cerevisiae, Jasmin Philip
Cdc6 Is Sequentially Regulated By Pp2a-Cdc55, Cdc14, And Sic1 For Origin Licensing In S. Cerevisiae, Jasmin Philip
Dissertations, Theses, and Capstone Projects
Control of DNA replication is critical for progression of the cell cycle and genomic stability. Cyclin-dependent kinases (CDKs) coordinate numerous phosphorylation events to accomplish two biological tasks for all living organisms: DNA replication and cell division. One CDK, Cyclin-Cdc28, is responsible for cell cycle progression in budding yeast. DNA replication requires a stepwise assembly of the pre-replicative complex on DNA, including Orc1-6, Cdc6, Cdt1 and Mcm2-7, during M-G1 phase. Cdc6 contains eight Cdc28 consensus sites, SP or TP motifs. Clb5-Cdc28 phosphorylates Cdc6-T7 to recruit Cks1, the Cdc28 phospho-adaptor, for subsequent multisite phosphorylation during S phase. There are two phospho-degrons at …
Cryo-Em Structure Of Mechanosensitive Channel Ynai Using Sma2000: Challenges And Opportunities, Claudio Catalano, Danya Ben-Hail, Weihua Qiu, Paul Blount, Amedee Des Georges, Youzhong Guo
Cryo-Em Structure Of Mechanosensitive Channel Ynai Using Sma2000: Challenges And Opportunities, Claudio Catalano, Danya Ben-Hail, Weihua Qiu, Paul Blount, Amedee Des Georges, Youzhong Guo
Publications and Research
Mechanosensitive channels respond to mechanical forces exerted on the cell membrane and play vital roles in regulating the chemical equilibrium within cells and their environment. Highresolution structural information is required to understand the gating mechanisms of mechanosensitive channels. Protein-lipid interactions are essential for the structural and functional integrity of mechanosensitive channels, but detergents cannot maintain the crucial native lipid environment for purified mechanosensitive channels. Recently, detergent-free systems have emerged as alternatives for membrane protein structural biology. This report shows that while membrane-active polymer, SMA2000, could retain some native cell membrane lipids on the transmembrane domain of the mechanosensitive-like YnaI channel, …
Study Of The Gain-Of-Function Mutant P53 And Parp1 In Triple-Negative Breast Cancer, Devon Lundine
Study Of The Gain-Of-Function Mutant P53 And Parp1 In Triple-Negative Breast Cancer, Devon Lundine
Dissertations, Theses, and Capstone Projects
Cancer cells often lose expression of the p53 protein or express mutant forms of p53. Some of these mutant p53 proteins, called gain-of-function mutant p53, have gained oncogenic functions. Previously, our group observed mutant p53 R273H interacts with replicating DNA and upregulates the chromatin localization of several DNA replication factors including PCNA, MCM2-7, and PARP1 (termed the mtp53-PARP-MCM axis). In this thesis, we explore the contribution of mutant p53 and PARP1 in castration-resistant prostate cancer (mutant p53 P223L and V274F) and triple-negative breast cancer (mutant p53 R273H). In the castration-resistant prostate cancer cell line DU145, we examine two mutant p53 …
The Structural And Functional Role Of Photosensing In Rgs-Lov Proteins, Zaynab Jaber
The Structural And Functional Role Of Photosensing In Rgs-Lov Proteins, Zaynab Jaber
Dissertations, Theses, and Capstone Projects
Light provides organisms with energy and spatiotemporal information. To survive and adapt, organisms have developed the ability to sense light to drive biochemical effects that underlie vision, entrainment of circadian rhythm, stress response, virulence, and many other important molecularly driven responses. Blue-light sensing Light-Oxygen-Voltage (LOV) domains are ubiquitous across multiple kingdoms of life and modulate various physiological events via diverse effector domains. Using a small molecule flavin chromophore, the LOV domain undergoes light-dependent structural changes leading to activation or repression of these catalytic and non-catalytic effectors. In silico analyses of high-throughput genomic sequencing data has led to the marked expansion …
Mitochondrial Distribution Of Glycine Receptors In Motor Neuron Cell Lines, Katsiaryna Milashevich
Mitochondrial Distribution Of Glycine Receptors In Motor Neuron Cell Lines, Katsiaryna Milashevich
Student Theses and Dissertations
Although non-essential, glycine plays an important role in major metabolic reactions and is most known for its anti-inflammatory effects. An accumulation of contemporary research has shown that glycine is able to stabilize membrane potential using glycine receptors at the cellular level and to protect mitochondrial function directly, whether it is from inflammation, heavy metal poisoning, or ischemia-induced neuroinflammation. In this research, the existence of a hypothetical mitochondrial glycine receptor is examined. Immunofluorescence imaging was used to examine the presence of the glycine receptor subunits alpha 1 and alpha 2 in both non- differentiated and differentiated neuroblastoma cell lines. The preliminary …
Unconventional Constituents And Shared Molecular Architecture Of The Melanized Cell Wall Of C. Neoformans And Spore Wall Of S. Cerevisiae, Christine Chrissian, Coney Pei-Chin Lin, Emma Camacho, Arturo Casadevall, Aaron M. Neiman, Ruth E. Stark
Unconventional Constituents And Shared Molecular Architecture Of The Melanized Cell Wall Of C. Neoformans And Spore Wall Of S. Cerevisiae, Christine Chrissian, Coney Pei-Chin Lin, Emma Camacho, Arturo Casadevall, Aaron M. Neiman, Ruth E. Stark
Publications and Research
The fungal cell wall serves as the interface between the cell and the environment. Fungal cell walls are composed largely of polysaccharides, primarily glucans and chitin, though in many fungi stress-resistant cell types elaborate additional cell wall structures. Here, we use solid-state nuclear magnetic resonance spectroscopy to compare the architecture of cell wall fractions isolated from Saccharomyces cerevisiae spores and Cryptococcus neoformans melanized cells. The specialized cell walls of these two divergent fungi are highly similar in composition. Both use chitosan, the deacetylated derivative of chitin, as a scaffold on which a polyaromatic polymer, dityrosine and melanin, respectively, is assembled. …
Probing The Limits Of Singular Gene Expression Through The Activity Of High Representation Odorant Receptor Transgenes, Eugene Lempert
Probing The Limits Of Singular Gene Expression Through The Activity Of High Representation Odorant Receptor Transgenes, Eugene Lempert
Dissertations, Theses, and Capstone Projects
Singular gene expression is a common phenomenon in biology, making its appearance in immunoglobulin selection, protocadherin expression, X chromosome-inactivation, random monoallelic expression, and olfactory receptor choice. Singularity involves an activation and a feedback step. The mechanisms of singular gene choice have some capacity to integrate additional member genes while still maintaining singularity, but will activate an additional member if an earlier choice was incapable of triggering the feedback step. Odorant Receptor (OR) genes are substantially divergent from each other in terms of coding sequence, promoter structure, and genomic locus, all of which plays a role in how many Olfactory Sensory …
Dictyostelium Discoideum Protein Kinase C-Orthologue Pkca Regulates The Actin Cytoskeleton Through Interaction With Phospholipase D And P21-Activated Kinase, Sean Singh
Dissertations, Theses, and Capstone Projects
Proper regulation of the actin cytoskeleton is crucial to many cellular processes. Many of these processes are regulated by extracellular signaling cues, which direct changes in the actin cytoskeleton, resulting in changes to cellular morphology, and directed motility. The social amoeba, Dictyostelium discoideum, is used as a simple model system to study the translation of extracellular signals to the actin cytoskeleton. When starved, these unicellular amoebae undergo a multicellular developmental process characterized by a tightly regulated sequence of signaling events. This results in chemotaxis and formation of a multicellular aggregate, and ultimately cell differentiation and the formation of a fruiting …
Towards A Mathematical Model Of Motility Using Dictyostelium Discoideum: Proteins And Geometric Features That Regulate Bleb-Based Motility, Zully Santiago
Towards A Mathematical Model Of Motility Using Dictyostelium Discoideum: Proteins And Geometric Features That Regulate Bleb-Based Motility, Zully Santiago
Dissertations, Theses, and Capstone Projects
A variety of biological functions depend on actin organization. The organization of actin is tightly regulated by a plethora of extracellular and intracellular signaling, scaffolding, and actin-binding proteins. Dysfunctions in this regulation lead to immune diseases, increased susceptibility to pathogens, neurodegenerative diseases, developmental disorders, and cancer metastasis. A variety of actin-dependent processes, including cell motility, are regulated by several proteins of interest: Paxillin, a scaffolding protein; WASP, an actin nucleating protein; SCAR/WAVE, another WASP family actin nucleating protein; Talin, a cortex-to-membrane binding protein; Myosin II, an F-actin contracting motor protein; and Protein Kinase C, a protein kinase. D. discoideum cells …
Inhibition Of Mitochondrial Permeability Transition By Deletion Of The Ant Family And Cypd, Jason Karch, Michael J. Bround, Hadi Khalil, Michelle A. Sargent, Nadina Latchman, Naohiro Terada, Pablo M. Peixoto, Jeffery D. Molkentin
Inhibition Of Mitochondrial Permeability Transition By Deletion Of The Ant Family And Cypd, Jason Karch, Michael J. Bround, Hadi Khalil, Michelle A. Sargent, Nadina Latchman, Naohiro Terada, Pablo M. Peixoto, Jeffery D. Molkentin
Publications and Research
The mitochondrial permeability transition pore (MPTP) has resisted molecular identification. The original model of the MPTP that proposed the adenine nucleotide translocator (ANT) as the inner membrane pore-forming component was challenged when mitochondria from Ant1/2 double null mouse liver still had MPTP activity. Because mice express three Ant genes, we reinvestigated whether the ANTs comprise the MPTP. Liver mitochondria from Ant1, Ant2, and Ant4 deficient mice were highly refractory to Ca2+-induced MPTP formation, and when also given cyclosporine A (CsA), the MPTP was completely inhibited. Moreover, liver mitochondria from mice with quadruple deletion of Ant1, Ant2, Ant4, and Ppif (cyclophilin …
The Role And Regulation Of Alternative Polyadenylation In The Dna Damage Response, Michael R. Murphy
The Role And Regulation Of Alternative Polyadenylation In The Dna Damage Response, Michael R. Murphy
Dissertations, Theses, and Capstone Projects
Cellular homeostasis is achieved by the dynamic flux in gene expression. Post-transcriptional regulation of coding and non-coding RNA offers a fast method of adapting to a changing cellular environment, including deadenylation, microRNA (miRNA) pathway, and alternative polyadenylation (APA). In this dissertation, I explored some of the mechanisms involved in the post-transcriptional regulation of gene expression. The main hypothesis in these studies is that a single APA event after DNA damage is governed by specific conditions and factors outside of current known regulators of APA, and that the resultant transcript has a role in the DNA damage response (DDR). My aims …
Deletion Of Mgr2p Affects The Gating Behavior Of The Tim23 Complex, Oygul Mirzalieva, Shinhye Jeon, Kevin Damri, Ruth Hartke, Layla Drwesh, Keren Demishtein-Zohary, Abdussalam Azem, Cory D. Dunn, Pablo M. Peixoto
Deletion Of Mgr2p Affects The Gating Behavior Of The Tim23 Complex, Oygul Mirzalieva, Shinhye Jeon, Kevin Damri, Ruth Hartke, Layla Drwesh, Keren Demishtein-Zohary, Abdussalam Azem, Cory D. Dunn, Pablo M. Peixoto
Publications and Research
The TIM23 complex is a hub for translocation of preproteins into or across the mitochondrial inner membrane. This dual sorting mechanism is currently being investigated, and in yeast appears to be regulated by a recently discovered subunit, the Mgr2 protein. Deletion of Mgr2p has been found to delay protein translocation into the matrix and accumulation in the inner membrane. This result and other findings suggested that Mgr2p controls the lateral release of inner membrane proteins harboring a stop-transfer signal that follows an N-terminal amino acid signal. However, the mechanism of lateral release is unknown. Here, we used patch clamp electrophysiology …
Mechanisms Adopted By Dengue-2 Viruses To Induce Autophagy In Mammalian Cells, Sounak Ghosh Roy
Mechanisms Adopted By Dengue-2 Viruses To Induce Autophagy In Mammalian Cells, Sounak Ghosh Roy
Dissertations, Theses, and Capstone Projects
Dengue, the most rapidly spreading flavivirus, threatens to affect almost half of the human global population. We previously showed that dengue-2 protects canine kidney cells (MDCK) from cytotoxic chemicals. We showed, independently, that cell protection, as well as viral replication and maturation, are positively regulated by PI3K-dependent autophagy. However, we had not identified the specific pathway that induces autophagy in infected cells. The current study explores the role of a specific branch of the endoplasmic reticulum (ER) stress-mediated Unfolded Protein Response (UPR), the PERK/eIF2α/ATF4 pathway in the induction of autophagy by …
Renal Risk Variants Of Apolipoprotein L-1 Form Channels At The Plasma Membrane That Lead To A Cytotoxic Influx Of Calcium, Joseph A. Giovinazzo
Renal Risk Variants Of Apolipoprotein L-1 Form Channels At The Plasma Membrane That Lead To A Cytotoxic Influx Of Calcium, Joseph A. Giovinazzo
Dissertations, Theses, and Capstone Projects
Apolipoprotein L-1 (APOL1) is a secreted protein that provides protection against several protozoan parasites due to its channel forming properties. Recently evolved variants, G1 and G2, increase kidney disease risk when present in two copies. In mammalian cells, overexpression of G1 and G2, but not wild-type G0, leads to swelling and eventual lysis. However, the mechanism of cell death remains elusive with multiple pathways being invoked, such as autophagic cell death mediated by a BH3 domain in APOL1, which we evaluated in this study. We hypothesized that the common trigger for these pathways is the APOL1 cation channel, which is …
Regulation Of The Tubulin Homolog Ftsz In Escherichia Coli, Monika S. Buczek
Regulation Of The Tubulin Homolog Ftsz In Escherichia Coli, Monika S. Buczek
Dissertations, Theses, and Capstone Projects
Escherichia coli is a well-known pathogen, and importantly, a widely used model organism in all fields of biological sciences for cloning, protein purification, and as a model for Gram-negative bacterial species. And yet, researchers do not fully understand how this bacterium replicates and divides. Every year additional division proteins are discovered, which adds complexity to how we understand E. coli undergoes cell division. Due to their specific roles in cytokinesis, some of these proteins may be potential targets for development of antibacterials or bacteriostatics, which are much needed for fighting the current global antibacterial deficit. My thesis work focuses on …
Mechanisms For Survival And Drug Resistance In Cancer Cells, Matthew B. Utter
Mechanisms For Survival And Drug Resistance In Cancer Cells, Matthew B. Utter
Dissertations, Theses, and Capstone Projects
PART I
Prostate cells are hormonally driven to grow and divide. Typical treatments for prostate cancer involve blocking the hormone androgen from activating the androgen receptor (AR) and thus inhibit growth and proliferation of the cancer. Androgen deprivation therapy (ADT) can lead to the selection of cancer cells that grow and divide independently of androgen receptor activation. Prostate cancer cells that are insensitive to androgens commonly display metastatic phenotypes and reduced long-term survival of patients. In this study, we provide evidence that androgen-insensitive prostate cancer cells have elevated phospholipase D (PLD) activity relative to the androgen-sensitive prostate cancer cells. PLD …
Wnt Secretion Proteins Modulate Rankl-Induced Expression Of Aire In Thymic Epithelial Cells, Daniel Pollack
Wnt Secretion Proteins Modulate Rankl-Induced Expression Of Aire In Thymic Epithelial Cells, Daniel Pollack
Dissertations and Theses
Thymic epithelial cells (TEC) are essential for a proper adaptive immune response by regulating thymocyte development and establishing central tolerance. In the thymus, TECs differentially express Wnt proteins, which activate canonical and non-canonical Wnt signaling pathways. Wnt signaling is thought to regulate cell survival, proliferation, and development although the direct molecular mechanisms in TECs have yet to be elucidated. The inducible inhibition of canonical Wnt signaling with Dkk1 leads to a rapid loss of TEC progenitors as well as a decline in mature Aire-expressing mTECs. Therefore, we explore the role of Wnt ligands potentially responsible for stimulating and/or regulating Wnt …
Molecular Analysis Of Ftsz-Ring Assembly In E. Coli Cytokinesis, Kuo-Hsiang Huang
Molecular Analysis Of Ftsz-Ring Assembly In E. Coli Cytokinesis, Kuo-Hsiang Huang
Dissertations, Theses, and Capstone Projects
An essential first step in bacterial division is the assembly of a cytokinetic ring (Z-ring) formed by the tubulin-like FtsZ at midcell. The highly conserved core domain of FtsZ has been reported to mediate assembly of FtsZ polymers in vivo and in vitro. Species-specific differences in the FtsZ C-terminal domain such as the FtsZ CTV region and interactions with several modulatory proteins such as ZapC and ZapD, restricted to certain bacterial classes, also serve as key determinants of FtsZ protofilament bundling. Here, we characterize (i) the roles of the FtsZ CTV region in mediating both longitudinal and lateral interactions …
Polymerase Alpha Components Associate With Telomeres To Mediate Overhang Processing, Raffaella Diotti
Polymerase Alpha Components Associate With Telomeres To Mediate Overhang Processing, Raffaella Diotti
Dissertations, Theses, and Capstone Projects
Telomeres consist of TTAGGG repeats, which end with a 3' G-overhang and are bound by a six-protein complex, known as Shelterin. In humans, telomeres shorten at each cell division, unless telomerase is expressed and able to add telomeric repeats to the 3' G-overhang. However, for effective telomere maintenance, the DNA strand complementary to that made by telomerase must be synthesized. In this study, I focused on the Polα/primase complex, in particular the subunits p68 (POLA2, the regulatory subunit) and p180 (Polα, the catalytic subunit), and their potential roles at telomeres. I was able to detect p180, p68 and OBFC1, a …
The Sex Of The Cell Dictates Its Response, Carlos Ganesh Penaloza
The Sex Of The Cell Dictates Its Response, Carlos Ganesh Penaloza
Dissertations, Theses, and Capstone Projects
Male and female differences in frequency of occurrence in disease have perplexed scientists for some time. This in part derives from limitations in the systems in which one can evaluate sex differences. At the organismal level, differences can be hidden by a myriad of extensive and complex factors. Additional limitations exist since most biomedical studies are performed almost exclusively on male subjects, as the female hormonal milieu is intrinsically more variable and too troublesome for routine inclusion in research protocols. Research documenting sex differences continues to grow, and while most researchers suggests that sex hormones are at the core of …