Open Access. Powered by Scholars. Published by Universities.®

Molecular Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 15 of 15

Full-Text Articles in Molecular Biology

Characterization Of A Putative Helicase In Rifampicin Resistance Of Mycobacterium Abscessus:, Aavrati Saxena May 2021

Characterization Of A Putative Helicase In Rifampicin Resistance Of Mycobacterium Abscessus:, Aavrati Saxena

Legacy Theses & Dissertations (2009 - 2024)

Mycobacterium abscessus (Mab), a non-tuberculous environmental mycobacterium is one of the emerging pathogens. The number of Mab infections has doubled in the past decade. It is also an opportunistic pathogen usually infecting immunocompromised individuals and causing numerous skin and soft tissue infections. It commonly causes lung infections in people who are already infected with one or other lung infections such as tuberculosis. The treatment of Mab infections is difficult because of its intrinsic resistance to most of the antibiotics available. This project studies Rifampicin (RIF) resistance in Mab, as RIF is a well-established treatment for other mycobacterial infections including tuberculosis, …


Retrotransposon-Mediated Transduction Of An Environmental Cue To Regulate Centrosome Fate, Shawn Patrick Murphy Jan 2021

Retrotransposon-Mediated Transduction Of An Environmental Cue To Regulate Centrosome Fate, Shawn Patrick Murphy

Legacy Theses & Dissertations (2009 - 2024)

In 1969, the enrichment of mobile element repeat sequences led Britton and Davidson to propose the hypothesis that gene expression in higher eukaryotes is regulated through the exaptation of mobile elements. In this work, I have explored the hypothesis that mobile elements can also be harnessed by the host to regulate asymmetric cell division, thereby determining cell fate. Retrotransposons are ubiquitous eukaryotic mobile elements that transpose through an RNA intermediate. They are often active in cell types that divide asymmetrically to yield daughter cells with different fates, such as embryonic stem cells, germline stem cells, neuronal stem cells and the …


Premature Rho-Dependent Transcription Termination In Escherichia Coli : Link To Translation And Gene Regulation, Gabriele Baniulyte Jan 2019

Premature Rho-Dependent Transcription Termination In Escherichia Coli : Link To Translation And Gene Regulation, Gabriele Baniulyte

Legacy Theses & Dissertations (2009 - 2024)

Transcription termination factor Rho is an essential protein in Escherichia coli and related bacteria. The primary function of Rho is to clear unproductive RNA polymerases from the DNA template to minimize negative effects associated with uncontrolled transcription. Although most of the Rho termination events are constitutive, premature Rho-mediated termination was observed at 3% of all affected transcripts indicating active regulation of Rho activity. In this work, we investigated the regulatory mechanism behind premature Rho-dependent transcription termination in two unrelated genes: suhB and topAI. We show that in both cases transcription is terminated inside the coding gene as a consequence of …


Influence Of The Pre-Initiation Complex On Mediator Recruitment In Saccharomyces Cerevisiae, Elisabeth Rose Knoll Jan 2017

Influence Of The Pre-Initiation Complex On Mediator Recruitment In Saccharomyces Cerevisiae, Elisabeth Rose Knoll

Legacy Theses & Dissertations (2009 - 2024)

The Mediator complex plays a central, highly conserved role in eukaryotic transcription by RNA Polymerase II (Pol II) by stimulating the cooperative assembly of a pre-initiation complex (PIC) and recruitment of Pol II for gene activation. Mediator recruitment has generally been ascribed to sequence-specific activators engaging subunits from the tail module which in turn function to recruit the middle and head for complete assembly at the UAS. Mediator subunits of the middle and head then bridge the enhancer to connect with the PIC at the core promoter. It is reported that Mediator recruitment at the UAS preferentially occurs at SAGA-dependent, …


The Role Of The Mediator Transcriptional Co-Activator Complex And Promoter Dependence In Ty1 Retrotransposition In Saccharomyces Cerevisiae, Alicia Salinero Jan 2017

The Role Of The Mediator Transcriptional Co-Activator Complex And Promoter Dependence In Ty1 Retrotransposition In Saccharomyces Cerevisiae, Alicia Salinero

Legacy Theses & Dissertations (2009 - 2024)

Retrotransposons are mobile genetic elements that replicate via an RNA intermediary and constitute a significant portion of most eukaryotic genomes. Saccharomyces cerevisiae has been invaluable to retrotransposon research due to the presence of an active retroelement known as Ty1. The mobility of Ty1 is regulated both positively and negatively by numerous host factors, including several subunits of the Mediator transcriptional co-activator complex. The Mediator core complex is organized into genetically and structurally defined head, middle, and tail modules, along with a transiently associated kinase module. We show that with the exception of the kinase module, deletion of non-essential subunits from …


Altered Lipid Metabolism And Adipocyte Activity Support Her2+ Breast Cancer Progression, Jason Wong Jan 2017

Altered Lipid Metabolism And Adipocyte Activity Support Her2+ Breast Cancer Progression, Jason Wong

Legacy Theses & Dissertations (2009 - 2024)

Overexpression of HER2 (ERBB2/neu) in breast cancer is an established clinical marker for aggressive disease and increased mortality. HER2+ breast cancers have increased protein levels of Human Epidermal Growth Factor Receptor 2 and overexpression of its coding gene, ERBB2. Many HER2+ tumors feature concomitant co-expression of the Nuclear Receptor subfamily 1, Group D, Member 1 (NR1D1/RevERBα) which regulates adipogenesis and circadian rhythm; the dysregulation of these two processes are known risk factors for breast cancer. HER2+ breast cancer cells have increased lipid synthesis, with evidence suggesting that NR1D1 is responsible for the upregulation of several genes in the de novo …


Genome-Scale Analyses Of Transcription And Transcriptional Regulation In Bacteria, Devon Marie Fitzgerald Jan 2015

Genome-Scale Analyses Of Transcription And Transcriptional Regulation In Bacteria, Devon Marie Fitzgerald

Legacy Theses & Dissertations (2009 - 2024)

The textbook model of bacterial transcription regulation posits that promoters occur immediately upstream of genes and that transcription factors (TFs) modulate transcription through promoter-proximal binding. However, the recent application of unbiased genome-wide approaches, such as ChIP-seq and RNA-seq, has revealed a much more complex picture, including TF binding and transcription initiation occurring in unexpected locations. This dissertation describes the use of deep sequencing-based approaches to evaluate the genome-wide binding of transcription-related proteins and identify locations of transcription initiation. I have assessed the genome-wide binding of three Escherichia coli TFs and an alternative σ factor. Additionally, I have analyzed genome-wide patterns …


Regulation Of Ty1 Retrovirus-Like Transposon Rna Localization And Translation, Ryan Joseph Palumbo Jan 2014

Regulation Of Ty1 Retrovirus-Like Transposon Rna Localization And Translation, Ryan Joseph Palumbo

Legacy Theses & Dissertations (2009 - 2024)

Replication of the Ty1 retrovirus-like transposon of the yeast Saccharomyces cerevisiae is stringently regulated to reduce the frequency of deleterious retrotransposition events. However, under stress conditions, Ty1 retrotransposition can lead to adaptive genomic alterations. To characterize host regulation of Ty1 retrotransposition, I analyzed ribosome profiling data and showed that Ty1 RNA is efficiently translated. Moreover, the ribosome biogenesis factors BUD21, DBP7, HCR1, LOC1, MRT4, and PUF6 are required for optimal expression of the Ty1 protein Gag.


Molecular Actions Of The Vitamin D Receptor In Breast Cancer, Erika Laporta Jan 2014

Molecular Actions Of The Vitamin D Receptor In Breast Cancer, Erika Laporta

Legacy Theses & Dissertations (2009 - 2024)

1,25-Dihydroxyvitamin D (1,25D) exerts anti-cancer actions through the vitamin D receptor (VDR) but the specific targets that mediate these effects remain to be defined. In these studies, growth and genomic responses to 1,25D were evaluated in a cellular model system derived from mammary tumors generated in VDR knockout (KO) and wildtype (WT) mice. WT145 cells (derived from WT tumors) expressed VDR and were growth inhibited by 1,25D, whereas KO240 cells (derived from VDRKO tumors) lacked VDR and were not growth inhibited by 1,25D. KO240 cell clones stably expressing VDR (KOhVDR cells) were sensitized to 1,25D mediated growth arrest. Genomic profiling …


The Role Of Chromatin And Cofactors In The Transcriptional Memory Effect Exerted In Saccharomyces Cerevisiae, Emily Leigh Paul Jan 2012

The Role Of Chromatin And Cofactors In The Transcriptional Memory Effect Exerted In Saccharomyces Cerevisiae, Emily Leigh Paul

Legacy Theses & Dissertations (2009 - 2024)

Abf1 and Rap1 are functionally similar general regulatory factors (GRFs) found in Saccharomyces cerevisiae . Abf1, in its role as a transcriptional activator, exerts a memory effect on some genes under its control. This effect results in transcription levels remaining steady when Abf1 dissociates from its binding site in a conditional mutant. In contrast, Rap1 fails to elicit the same effect on its regulatory targets. Transcriptional memory effects have been observed in many fields of study, including immunology, cancer, and stem cells, and conservation of transcription machinery will allow studies in yeast to be applied to higher organisms.


The Role Of Ess1 In Survival, Morphogenetic Switching And Transcription In The Fungal Pathogen Candida Albicans, Dhanushki Poornima Samaranayake Jan 2012

The Role Of Ess1 In Survival, Morphogenetic Switching And Transcription In The Fungal Pathogen Candida Albicans, Dhanushki Poornima Samaranayake

Legacy Theses & Dissertations (2009 - 2024)

Candida albicans is a fungal pathogen that causes serious infections among immune-compromised patients and premature infants. C. albicans can become drug resistant, therefore, identifying new antifungal drug targets is an important goal. Here, we study a peptidyl-prolyl cis/trans isomerase called Ess1 as a potential drug target. Ess1 is conserved among pathogenic fungi, and therefore, potential inhibitors of Ess1 should display a broad spectrum of activity. We confirm that Ess1 is essential for growth in Candida albicans, but unlike the previously published find, deleting one copy of the C. albicans ESS1 gene did not affect morphogenetic switching. However, further reducing activity …


The Role Of Trm9 In Stress Responses, Ashish Ravindra Patil Jan 2011

The Role Of Trm9 In Stress Responses, Ashish Ravindra Patil

Legacy Theses & Dissertations (2009 - 2024)

Cells need to respond appropriately to environmental changes in order to maintain homeostasis. The cellular response to an environmental stress is regulated at transcriptional, translational and post translational levels. The tRNA, which acts as an adaptor molecule between the mRNA and the protein, plays an important role in the translational regulation of cellular responses to stress and is one of the most heavily modified biomolecules. In Saccharomyces cerevisiae , the wobble uracil of the tRNA(3'-UCU-5') Arg, tRNA(3'-UUC-5') Glu and certain other specific tRNAs are modified to 5-methoxycarbonylmethyluridine (mcm5U) and 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U) residues by the tRNA methyltransferase 9 (Trm9). Modifications at …


Group Ii Intron Dynamics In Heterologous Hosts, Venkata Raghavendra Aditya Chalamcharla Jan 2010

Group Ii Intron Dynamics In Heterologous Hosts, Venkata Raghavendra Aditya Chalamcharla

Legacy Theses & Dissertations (2009 - 2024)

Group II introns are ribozymes with an innate ability to self-splice. They are found predominantly in bacterial and bacterial-derived organellar genomes, but not in the nuclear genomes of eukaryotes. In bacteria, group II introns often behave as mobile retroelements, invading host DNA and exploiting its machinery to complete the retromobility process. The object of my studies is the group II intron found in the Lactococcus lactis relaxase gene. To determine the nature of the group II intron-host relationship, we performed a genetic screen and identified several host factors that affect group II intron retromobility in Escherichia coli, which provides a …


Role Of Cyp2a5 In Drug Metabolism, Chemical Toxicity, And Maintenance Of Steroid Hormone Homeostasis : Insights From Studies On A Novel Cyp2a5-Null Mouse Model, Xin Zhou Jan 2009

Role Of Cyp2a5 In Drug Metabolism, Chemical Toxicity, And Maintenance Of Steroid Hormone Homeostasis : Insights From Studies On A Novel Cyp2a5-Null Mouse Model, Xin Zhou

Legacy Theses & Dissertations (2009 - 2024)

The central hypothesis is that CYP2A5 plays an important role in the metabolism of xenobiotic substrates, and in the toxicity induced by over-exposure to drugs, as well as in the metabolism of endogenous compounds and regulation of steroid hormone homeostasis. The specific aims are: 1) to generate and characterize a Cyp2a5-null mouse; 2) to determine the role of CYP2A5 in the systemic clearance of nicotine and cotinine; and 3) to explore the mechanisms underlying the resistance of the lateral nasal gland (LNG) of male Cyp2g1-null/Cyp2a5-low mouse and Cyp2a5-null mouse to acetaminophen (AP) toxicity.


An Rnai Screen Targeting The Protein Tyrosine Kinases Identifies Bruton's Tyrosine Kinase (Btk) As A Breast Cancer Cell Survival Factor, Cheryl Lynne Eifert Jan 2009

An Rnai Screen Targeting The Protein Tyrosine Kinases Identifies Bruton's Tyrosine Kinase (Btk) As A Breast Cancer Cell Survival Factor, Cheryl Lynne Eifert

Legacy Theses & Dissertations (2009 - 2024)

The receptor protein tyrosine kinases (RPTKs) and the non- receptor protein tyrosine kinases (PTKs) are among the most commonly up-regulated genes found in all types of cancers. Although, a large body of data implicates a majority of tyrosine kinases (TKs) in cancer, few have been extensively evaluated for any potential therapeutic benefit in any of the many subtypes of breast cancer. We have used RNA interference (RNAi) to perform a large-scale loss-of-function analysis to facilitate the identification of individual factors necessary for the survival of an ErbB2 positive breast cancer cell line. We have found that 30% of the TKs …