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GSBS Dissertations and Theses

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Modulating Mcm Levels Causes Differential Loading At Origins Of Replication And Changes Replication Timing, Livio Dukaj Dec 2019

Modulating Mcm Levels Causes Differential Loading At Origins Of Replication And Changes Replication Timing, Livio Dukaj

GSBS Dissertations and Theses

DNA replication is a highly complex part of cell metabolism that ensures safe propagation of the genome through tight regulation of the expression, localization, and activity of a large number of factors. Replication starts from distinct sites in the genome and initiation events are temporally ordered in a manner that is, on average, highly reproducible across cell populations. The specific order with which different parts of the genome are replicated has been proposed to be important to processes such as gene expression, cell differentiation, development, and genome evolution. Nevertheless, the fundamental mechanisms that are responsible for establishing these timing programs ...


Robustness Mechanisms Of Temporal Cell-Fate Progression In C. Elegans, Orkan Ilbay Dec 2019

Robustness Mechanisms Of Temporal Cell-Fate Progression In C. Elegans, Orkan Ilbay

GSBS Dissertations and Theses

Robustness is a ubiquitous property of biological systems, however, underlying mechanisms that help reinforce the optimal phenotypes despite environmental or physiological perturbations are poorly understood.

C. elegans development consists of four larval stages (L1-L4) and well-characterized invariant cell lineages, within which the heterochronic pathway controls the order and timing of cell-fates. Environmental or physiological stress signals can slow or temporarily halt larval stage progression; remarkably, however, temporal cell-fate progression remains unaffected.

We show that two widely conserved signaling pathways, insulin and TGF- β, that regulate C. elegans larval stage progression in response to starvation and crowding, respectively, also regulate a ...


Intron And Small Rna Localization In Mammalian Neurons, Harleen Saini Jul 2019

Intron And Small Rna Localization In Mammalian Neurons, Harleen Saini

GSBS Dissertations and Theses

RNA molecules are diverse in form and function. They include messenger RNAs (mRNAs) that are templates for proteins, splice products such as introns that can generate functional noncoding RNAs, and a slew of smaller RNAs such as transfer RNAs (tRNAs) that help decode mRNAs into proteins. RNAs can show distinct patterns of subcellular localization that play an important role in protein localization. However, RNA distribution in cells is incompletely understood, with prior studies focusing primarily on RNAs that are long (>200 nucleotides), fully processed, and polyadenylated. We examined the distribution of RNAs in neurons. Neuronal compartments can be separated by ...


Identification Of Essential Genes In Hepatocellular Carcinomas Using Crispr Screening, Ankur Sheel Jul 2019

Identification Of Essential Genes In Hepatocellular Carcinomas Using Crispr Screening, Ankur Sheel

GSBS Dissertations and Theses

Hepatocellular carcinoma (HCC) is an aggressive subtype of liver cancer with a poor prognosis. Currently, prognosis for HCC patients remains poor as few therapies are available. The clinical need for more effective HCC treatments remains unmet partially because HCC is genetically heterogeneous and HCC driver genes amenable to targeted therapy are largely unknown. Mutations in the TP53 gene are found in ~30% of HCC patients and confer poor prognosis to patients. Identifying genes whose depletion can inhibit HCC growth, and determining the mechanisms involved, will aid the development of targeted therapies for HCC patients. Therefore, the first half of this ...


Mechanistic Basis For Control Of Early Embryonic Development By A 5’ Trna Fragment, Xin Y. Bing Jul 2019

Mechanistic Basis For Control Of Early Embryonic Development By A 5’ Trna Fragment, Xin Y. Bing

GSBS Dissertations and Theses

Ancestral environmental conditions can instruct offspring development, although the mechanism(s) underlying such transgenerational epigenetic inheritance is unclear. In murine models focused on paternal dietary effects, we and others have identified tRNA fragments (tRFs) in mature sperm as potential carriers of epigenetic information. In our search for molecular targets of specific tRFs, we observed that altering the level of 5’-tRF Glycine-GCC (tRF-GG) in mouse embryonic stem cells (mESCs) and preimplantation embryos modulates the expression of the endogenous retrovirus MERV-L and genes regulated by MERV-L. Intriguingly, transient derepression of MERV-L is associated with totipotency of two-cell stage embryos and a ...


Tcr Signal Strength Controls Dynamic Nfat Activation Threshold And Graded Irf4 Expression In Cd8+ T Cells, James M. Conley Apr 2019

Tcr Signal Strength Controls Dynamic Nfat Activation Threshold And Graded Irf4 Expression In Cd8+ T Cells, James M. Conley

GSBS Dissertations and Theses

TCR signal strength is critical for CD8+ T cell clonal expansion after antigen stimulation. Levels of the transcription factor IRF4 control the magnitude of this process through induction of genes involved in proliferation and glycolytic metabolism. The signaling mechanism connecting graded TCR signaling to the generation of varying amounts of IRF4 is not well understood. Here, using multiple methods to vary TCR signal strength and measure changes in transcriptional activation in single CD8+ T cells, we connect antigen potency to the kinetics of NFAT activation and Irf4 mRNA expression. T cells that transduce weaker TCR signals exhibit a marked delay ...


Understanding The Role Of Prdm12b In Zebrafish Development, Ozge Yildiz Mar 2019

Understanding The Role Of Prdm12b In Zebrafish Development, Ozge Yildiz

GSBS Dissertations and Theses

Function of the adult nervous system relies on the appropriate establishment of neural circuits during embryogenesis. In vertebrates, the neurons that make up motor circuits form in distinct domains along the dorsoventral (DV) axis of the neural tube. Each domain is characterized by a unique combination of transcription factors (TFs) that promote a specific fate, while repressing the fates of adjacent domains. The prdm12 TF is required for the expression of eng1b and the generation of V1 interneurons in the p1 domain, but the details of its function remain unclear.

We used CRISPR/Cas9 genome editing technology to generate the ...


Identification Of Deubiquitinating Enzymes That Control The Cell Cycle In Saccharomyces Cerevisiae, Claudine E. Mapa Nov 2018

Identification Of Deubiquitinating Enzymes That Control The Cell Cycle In Saccharomyces Cerevisiae, Claudine E. Mapa

GSBS Dissertations and Theses

A large fraction of the proteome displays cell cycle-dependent expression, which is important for cells to accurately grow and divide. Cyclical protein expression requires protein degradation via the ubiquitin proteasome system (UPS), and several ubiquitin ligases (E3) have established roles in this regulation. Less is understood about the roles of deubiquitinating enzymes (DUB), which antagonize E3 activity. A few DUBs have been shown to interact with and deubiquitinate cell cycle-regulatory E3s and their protein substrates, suggesting DUBs play key roles in cell cycle control. However, in vitro studies and characterization of individual DUB deletion strains in yeast suggest that these ...


Characterization Of The Caspase-3 Cleavage Motif Of The Salmonella Typhimurium Effector Protein Sifa And Its Role In Pathogenesis, Samir Patel Nov 2018

Characterization Of The Caspase-3 Cleavage Motif Of The Salmonella Typhimurium Effector Protein Sifa And Its Role In Pathogenesis, Samir Patel

GSBS Dissertations and Theses

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a Gram-negative facultative anaerobe that induces severe inflammation resulting in gastroenteritis. In the case of S. Typhimurium infection, induction of an inflammatory response has been linked to its primary virulence mechanism, the type III secretion system (T3SS). The T3SS secretes protein effectors that exploit the host’s cell biology to facilitate bacterial entry and intracellular survival, and to modulate the host immune response.

One such effector, SifA, is a bi-functional T3SS effector protein that plays an important role in Salmonella virulence. The N-terminal domain of SifA binds SifA-Kinesin-Interacting-Protein (SKIP), and via an interaction ...


The Relationship Between Inhibition, Conformation, And Catalysis Of The Aminopeptidase Erap1, Zachary Maben Nov 2018

The Relationship Between Inhibition, Conformation, And Catalysis Of The Aminopeptidase Erap1, Zachary Maben

GSBS Dissertations and Theses

ERAP1 is an aminopeptidase that is a component of antigen processing. To distinguish the role of ERAP1 from homologs ERAP2 and IRAP, I identified three specific ERAP1 inhibitors via a high-throughput screen. These compounds inhibit hydrolysis of a decamer peptide, and some inhibit ERAP1 in a cellular assay. These inhibitors enable dissection of ERAP1 mechanism. ERAP1 has been crystallized in two conformations: open and closed. I collected SAXS data on ERAP1 in the presence of various inhibitors. ERAP1 adopts an open conformation in solution, but some inhibitors stabilize the closed form. Compound 3 docks to a distal pocket 28Å from ...


Tumor-Stroma Interactions Differentially Alter Drug Sensitivity Based On The Origin Of Stromal Cells, Benjamin D. Landry Oct 2018

Tumor-Stroma Interactions Differentially Alter Drug Sensitivity Based On The Origin Of Stromal Cells, Benjamin D. Landry

GSBS Dissertations and Theses

Tumor heterogeneity observed between patients has made it challenging to develop universal or broadly effective cancer therapies. Therefore, an ever-growing movement within cancer research aims to tailor cancer therapies to individual patients or specific tumor subtypes. Tumor stratification is generally dictated by the genomic mutation status of the tumor cells themselves. Importantly, non-genetic influences – such as interactions between tumor cells and other components of the tumor microenvironment – have largely been ignored. Therefore, in an effort to increase treatment predictability and efficacy, we investigated how tumor-stroma interactions contribute to drug sensitivity and drug resistance.

I designed a high throughput co-culture screening ...


Transcriptional Regulation Of Effector And Memory Responses During Acute And Chronic Lymphocytic Choriomeningitis Virus (Lcmv) Infection, Elizabeth A. Olesin Oct 2018

Transcriptional Regulation Of Effector And Memory Responses During Acute And Chronic Lymphocytic Choriomeningitis Virus (Lcmv) Infection, Elizabeth A. Olesin

GSBS Dissertations and Theses

Transcriptional regulation of CD8+ T cell differentiation during acute and chronic viral infections is an intricate web made up of many of transcription factors. While several transcription factors have been elucidated in this process, there are still many more that remain elusive. In this work, we look into the role of two transcription factors, IRF4 and Runx2, and their role in CD8+ T cell terminal effector cells and memory precursor cells during acute LCMV-Armstrong infection. We found that IRF4 expression was regulated by TCR signal strength during infection, and that IRF4 expression levels directly correlated with the magnitude of the ...


Histone Deacetylase 3 (Hdac3) Regulates Lymphatic Vascular Development, Harish P. Palleti Janardhan Sep 2018

Histone Deacetylase 3 (Hdac3) Regulates Lymphatic Vascular Development, Harish P. Palleti Janardhan

GSBS Dissertations and Theses

Cardiovascular disease continues to be the leading cause of morbidity and mortality worldwide with an estimated 17 million annual deaths. A majority of cases are attributed to disease affecting the vascular system including arterial, venous and lymphatic vessels. Despite progress in understanding the molecular bases of vascular development and disease, the role of chromatin modifying enzymes in vascular processes remains ill defined. Here we show that the histone-modifying enzyme Hdac3 is a critical regulator of lymphatic vascular development. Endothelial specific loss of Hdac3 in mice affects the development of lymphovenous and lymphatic valves resulting in aberrant blood lymph separation, lymphedema ...


Illuminating Biology With Membrane Penetrating Sulfonate Delivery Scaffolds And Near-Infrared Azasiline Fluorophores, Adam Choi Sep 2018

Illuminating Biology With Membrane Penetrating Sulfonate Delivery Scaffolds And Near-Infrared Azasiline Fluorophores, Adam Choi

GSBS Dissertations and Theses

Near-infrared (NIR) light, with wavelengths of 650 to 900 nanometers, effectively penetrates tissues. The high signal to noise ratio and low phototoxicity of NIR light makes this wavelength range ideal for deep tissue imaging. However, current NIR fluorophores are generally large hydrophobic molecules that are prone to aggregation. Sulfonation can enhance aqueous solubility, but their anionic nature prevents membrane diffusion, and thus, restricts the applications of sulfonated molecules to in vitro or fixed cells.

The repertoire of commercially available sulfonated NIR probes is mostly limited cyanines, which have low photostability. Moreover, larger cyanines require multiple sulfonates to maintain aqueous solubility ...


Fluorescent Visualization Of Cellular Proton Fluxes, Lejie Zhang Sep 2018

Fluorescent Visualization Of Cellular Proton Fluxes, Lejie Zhang

GSBS Dissertations and Theses

Proton fluxes through plasma membranes are essential for regulating intracellular and extracellular pH and mediating co-transport of metabolites and ions. Although conventional electrical measurements are highly sensitive and precise for proton current detection, they provide limited specificity and spatial information. My thesis focuses on developing optical approaches to visualize proton fluxes from ion channels and transporters.

It has been demonstrated that channel-mediated acid extrusion causes proton depletion at the inner surface of the plasma membrane. Yet, proton dynamics at the extracellular microenvironment are still unclear. In Chapter II, we developed an optical approach to directly measure pH change in this ...


Investigation Of Lin-28 Function In Somatic Gonadal Development And Fertility, And Characterization Of The Lin-28 Isoforms In C. Elegans Hermaphrodites, Sungwook Choi Aug 2018

Investigation Of Lin-28 Function In Somatic Gonadal Development And Fertility, And Characterization Of The Lin-28 Isoforms In C. Elegans Hermaphrodites, Sungwook Choi

GSBS Dissertations and Theses

lin-28 was first characterized as a developmental timing regulator in Caenorhabditis elegans. Loss of lin-28 function (lin-28(lf)) mutants skip the hypodermal cell fates specific to the 2nd larval stage. Here, we studied two aspects of lin-28 which had not yet been investigated.

First, we show that lin-28(lf) mutants exhibit reduced fertility associated with abnormal somatic gonadal morphology. In particular, the abnormal spermatheca-uterine valve morphology of lin-28(lf) hermaphrodites traps embryos in the spermatheca, which disrupts ovulation and causes embryonic lethality. The same genes downstream of lin-28 in the regulation of hypodermal developmental timing also act downstream of ...


Fus And Excitotoxicity Cross Paths In Als: New Insights Into Cellular Stress And Disease, Maeve Tischbein Aug 2018

Fus And Excitotoxicity Cross Paths In Als: New Insights Into Cellular Stress And Disease, Maeve Tischbein

GSBS Dissertations and Theses

Amyotrophic lateral sclerosis (ALS) is an incurable and fatal neurodegenerative disease characterized by motor neuron loss. Although pathological mutations exist in >15 genes, the mechanism(s) underlying ALS are unknown. FUS is one such gene and encodes the nuclear RNA-binding protein (RBP), fused in sarcoma (FUS), which actively shuttles between the nucleus and cytoplasm. Intriguingly, nearly half of the ALS mutations identified in FUS cause this protein to mislocalize, suggesting that FUS localization is relevant to disease.

Here, we found that excitotoxicity, a neuronal stress caused by aberrant glutamate signaling, induces the rapid redistribution of FUS and additional disease-linked RBPs ...


Understanding Nuage-Mitochondrial Coupling In Drosophila Pirna Biogenesis, Tianfang Ge Aug 2018

Understanding Nuage-Mitochondrial Coupling In Drosophila Pirna Biogenesis, Tianfang Ge

GSBS Dissertations and Theses

In the Drosophilaovary, PIWI-interacting RNAs (piRNAs) suppress transposon expression, ensuring female fertility. PIWI proteins Aub and Ago3, loaded with ping-pong piRNAs and reside in perinuclear nuage granules, engage in reciprocal transposon transcript cleavage termed the ping-pong cycle. The other PIWI protein Piwi, loaded with phased piRNAs and resides in the nucleus, silences transposon transcriptionally. Ping-pong piRNAs are made through the ping-pong amplification loop by Aub and Ago3, whereas phased piRNAs are made through consecutive endonucleolytic cleavages that spread in 5′-to-3′ direction, presumably by Zucchini (Zuc), an endonuclease resides on the surface of mitochondria. The ping-pong and phasing biogenesis ...


Serinc5: Its Sensitivity To Nef And Restriction Of Hiv-1, Weiwei Dai Aug 2018

Serinc5: Its Sensitivity To Nef And Restriction Of Hiv-1, Weiwei Dai

GSBS Dissertations and Theses

The accessory protein Nef of human immunodeficiency virus type 1 (HIV-1) has long been known to enhance the infectivity of HIV-1 progeny virions. The multipass transmembrane proteins serine incorporator 3 (SERINC3) and SERINC5 were recently identified as novel antiviral proteins that restrict HIV-1 infectivity. Nef enhances HIV-1 infectivity by removing SERINCs from the plasma membrane, which prevents their incorporation into progeny HIV-1 virions. To exploit this potent intrinsic antiretroviral factor for potential therapy development, it is critical to explore the determinants in SERINC5 that govern its downregulation by Nef and its restriction on HIV-1 infectivity. Here I report that the ...


Ripplit And Chimeratie: High Throughput Tools For Understanding Higher Order Rnp Structures, Mihir Metkar Jul 2018

Ripplit And Chimeratie: High Throughput Tools For Understanding Higher Order Rnp Structures, Mihir Metkar

GSBS Dissertations and Theses

Even after their discovery more than 60 years ago, little is known about how messenger RNAs (mRNAs) are packaged inside the cells. To ensure efficient and accurate delivery of the intended message to its proper destination, it is important to package the informational molecule in a way that protects it from premature degradation but also proper decoding at the destination. However, very little is known about the this fundamentally important step of mRNA packaging inside eukaryotic cells. To this end, we developed a novel approach, RIPPLiT (RNA ImmunoPrecipitation and Proximity Ligation in Tandem), to capture the 3D architecture of the ...


Innate Detection Of Hiv-1 In Myeloid Dendritic Cells, Sean Matthew Mccauley Jul 2018

Innate Detection Of Hiv-1 In Myeloid Dendritic Cells, Sean Matthew Mccauley

GSBS Dissertations and Theses

Protective antiviral immune responses require priming of naïve T cells by dendritic cells (DCs) that have matured sufficiently to produce co-stimulatory cell surface molecules and cytokines. Although only low levels of productive HIV-1 infection are detected in ex vivo DCs following HIV-1 challenge, those few cells exhibit innate activation. Experimentally bypassing blocks to entry and replication leads to more efficient transduction of DCs and maturation as indicated by production of interferons and interferon stimulated genes. Furthermore, similar innate activation occurs upon transduction of macrophages or CD4+ T cells. However, the mechanism by which HIV-1 is detected to activate innate immune ...


Pie-1, Sumoylation, And Epigenetic Regulation Of Germline Specification In Caenorhabditis Elegans, Heesun Kim Jul 2018

Pie-1, Sumoylation, And Epigenetic Regulation Of Germline Specification In Caenorhabditis Elegans, Heesun Kim

GSBS Dissertations and Theses

In many organisms, the most fundamental event during embryogenesis is differentiating between germline cells and specialized somatic cells. In C. elegans, PIE-1 functions to protect the germline from somatic differentiation and appears to do so by blocking transcription and by preventing chromatin remodeling in the germline during early embryogenesis. Yet the molecular mechanisms by which PIE-1 specifies germline remain poorly understood. Our work shows that SUMOylation facilitates PIE-1-dependent germline maintenance and specification. In vivo SUMO purification in various CRISPR strains revealed that PIE-1 is SUMOylated at lysine 68 in the germline and that this SUMOylation is essential for forming NuRD ...


Studies In Antigen Presentation And Antigen Recognition At Different Interfaces Of The Adaptive Immune System, Maria P. Negroni Jul 2018

Studies In Antigen Presentation And Antigen Recognition At Different Interfaces Of The Adaptive Immune System, Maria P. Negroni

GSBS Dissertations and Theses

Antigen presentation and recognition are key processes of the immune system necessary to initiate the adaptive immune response. Longstanding goals of these fields have been to understand the molecular mechanism of MHC II-peptide binding, the way in which dysregulation of this process can lead to disease, and determining how γδTCRs recognize their ligands. To examine some of these outstanding questions, I designed photocleavable peptides that could bind HLA-DR1 and could be used to facilitate peptide exchange. I also performed studies to understand whether peptide exchange on HLA-DR1 can be affected by glycation modifications, which occur in hyperglycemic conditions such as ...


The Role Of Eukaryotic Abc-Transporters In Eliciting Neutrophil Infiltration During Streptococcus Pneumoniae Infection, Andrew Zukauskas Jun 2018

The Role Of Eukaryotic Abc-Transporters In Eliciting Neutrophil Infiltration During Streptococcus Pneumoniae Infection, Andrew Zukauskas

GSBS Dissertations and Theses

Streptococcus pneumoniae (S. pneumoniae) is a Gram-positive, encapsulated bacterium capable of causing significant morbidity and mortality throughout the world. A hallmark of S. pneumoniae infection is infiltration of neutrophils (PMNs) that assist in controlling the spread infection but may also contribute to pathology. Paradoxically, studies have shown that limiting PMN infiltration into the lumen of the lung during infection actually betters clinical outcome in experimental S. pneumoniae infection. The final step in PMN luminal trafficking is a Hepoxilin A3 (HXA3)-dependent migration across the pulmonary epithelium. HXA3 is a PMN chemoattractant that forms gradients along the polarized epithelial ...


Investigating The Gene Regulatory Network Underlying Caudal Hindbrain Specification In Embryonic Zebrafish, Priyanjali Ghosh Jun 2018

Investigating The Gene Regulatory Network Underlying Caudal Hindbrain Specification In Embryonic Zebrafish, Priyanjali Ghosh

GSBS Dissertations and Theses

To understand the gene regulatory network (GRN) governing caudal hindbrain formation in embryonic zebrafish, several early expressed factors have been manipulated, and multiple genetic mutants have been characterized. Such analyses have identified morphogens such as Retinoic Acid (RA) and Fibroblast growth factors (FGFs), as well as transcription factors like hoxb1b, hoxb1a, hnf1ba, and valentino as being required for rhombomere (r) r4-r6 formation in zebrafish. Considering that the caudal hindbrain is relatively complex – for instance, unique sets of neurons are formed in each rhombomere segment – it is likely that additional essential genes remain to be identified and integrated into the caudal ...


An Examination Of Mhc, Peptide, And Tcr Interactions, Peter Trenh May 2018

An Examination Of Mhc, Peptide, And Tcr Interactions, Peter Trenh

GSBS Dissertations and Theses

T cell receptors (TCR) bind to peptides from various sources on MHC (Major Histocompatibility Complex) molecules. A long-standing goal in the field is to understand the mechanisms of MHC-peptide exchange and MHC-TCR interactions. Here, I present work from three uniquely different systems that address the following: HLA-DR1 conformational stability, self-tolerant mechanisms of TCRs isolated from self-reactive TCR transgenic mice, and TCR cross-reactivity mechanisms between LCMV and VV.

First, I present a crystal structure of HLA-DR1 in complex with A1L9 peptide, a peptide with two amino acid substitutions from the parental peptide. The singly substituted A1 peptide, which has a pocket ...


Maelstrom Represses Canonical Rna Polymerase Ii Transcription In Drosophila Dual-Strand Pirna Clusters, Timothy H. Chang Apr 2018

Maelstrom Represses Canonical Rna Polymerase Ii Transcription In Drosophila Dual-Strand Pirna Clusters, Timothy H. Chang

GSBS Dissertations and Theses

Transposons constitute much of the animal genome. While many transposons are ancient and inactivated, numerous others are intact and must be actively repressed. Uncontrolled transposons can cause genomic instability through DNA damage or mutations and must be carefully silenced in the germline or risk sterility or mutations that are passed on to offspring.

In Drosophila melanogaster, 23–30 nt long piRNAs direct transposon silencing by serving as guides for Aubergine, Argonaute3, and Piwi, the three fly PIWI proteins. piRNAs derive from piRNA clusters—large heterochromatic DNA loci comprising transposons and transposon fragments. piRNAs are loaded into PIWI proteins via the ...


Targeting Drug Resistance In Hcv Ns3/4a Protease: Mechanisms And Inhibitor Design Strategies, Ashley N. Matthew Apr 2018

Targeting Drug Resistance In Hcv Ns3/4a Protease: Mechanisms And Inhibitor Design Strategies, Ashley N. Matthew

GSBS Dissertations and Theses

The Hepatitis C virus (HCV) NS3/4A protease inhibitors (PIs) have become a mainstay of newer all-oral combination therapies. Despite improvements in potency of this inhibitor class, drug resistance remains a problem with the rapid emergence of resistance-associated substitutions (RASs). In this thesis I elucidate the molecular mechanisms of drug resistance for PIs against a resistant variant and apply insights toward the design of inhibitors with improved resistance profiles using structural, biochemical and computational techniques. Newer generation PIs retain high potency against most single substitutions in the protease active site by stacking on the catalytic triad. I investigated the molecular ...


A Suite Of Computational Tools To Interrogate Sequence Data With Local Haplotype Analysis Within Complex ​Plasmodium​ Infections And Other Microbial Mixtures, Nicholas J. Hathaway Mar 2018

A Suite Of Computational Tools To Interrogate Sequence Data With Local Haplotype Analysis Within Complex ​Plasmodium​ Infections And Other Microbial Mixtures, Nicholas J. Hathaway

GSBS Dissertations and Theses

The rapid development of DNA sequencing technologies has opened up new avenues of research, including the investigation of population structure within infectious diseases (both within patient and between populations). In order to take advantage of these advances in technologies and the generation of new types of data, novel bioinformatics tools are needed that won’t succumb to artifacts introduced by the data generation, and thus provide accurate and precise results. To achieve this goal I have create several tools.

First, SeekDeep, a pipeline for analyzing targeted amplicon sequencing datasets from various technologies, is able to achieve 1-base resolution even at ...


Role Of Trip6 And Angiomotins In The Regulation Of The Hippo Signaling Pathway, Shubham Dutta Mar 2018

Role Of Trip6 And Angiomotins In The Regulation Of The Hippo Signaling Pathway, Shubham Dutta

GSBS Dissertations and Theses

Mechanical tension is an important regulator of cell proliferation, differentiation, migration and cell death. It is involved in the control of tissue architecture and wound repair and its improper sensing can contribute to cancer. The Hippo tumor suppressor pathway was recently shown to be involved in regulating cell proliferation in response to mechanical tension. The core of the pathway consists of the kinases MST1/2 and LATS1/2, which regulate the target of the pathway, the transcription co-activator YAP/ TAZ (hereafter referred to as YAP). When the Hippo pathway is inactive, YAP remains in the nucleus and promotes cell proliferation ...