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Single Cell Lineage Tracing Reveals Mechanisms Of Tumor Initiation And Chemoresistance In Small Cell Lung Cancer, Hannah Wollenzien

Dissertations and Theses

Small Cell Lung Cancer (SCLC) is a devastating disease characterized by a very low two-year survival rate and almost universal acquisition of chemoresistance. Nearly all patients have tumors driven by functional inactivation of the tumor suppressors Rb and p53, but despite the uniform origins of this tumor, not all patients are genetically or phenotypically identical. SCLC can be subtyped into four unique molecular subtypes, determined by the expression of ASCL1, NEUROD1, POU2F3, or YAP1. These subtypes are plastic, and subtype switching after chemotherapy has been documented. Without the understanding of how tumor heterogeneity arises, we cannot solve the challenge of …

Expanding Metabolic Diversity Of Two Archaeal Phyla: Nanoarchaeota And Korarchaeota, John Forad Kelley

Dissertations and Theses

Culture independent studies have revealed a greater diversity of Archaea than the two kingdoms initially defined by Carl Woese. Culturing species from the newly discovered archaeal lineages, as with the majority of microbes, has been difficult. To overcome the culturing dilemma, metagenomics is being used to reconstruct environmental genomes. Two metagenomic studies are presented in this thesis, with the aim of recovering newly proposed archaeal genomes from the Nanoarchaeota and Korarchaeota.

In the first study, a sediment sample, NZ13, was collected from a terrestrial New Zealand hot spring. Along with the sediment sample, two complex enrichments were sequenced on an …

Evolution And Metabolic Potential Of Francisella-Like Endosymbionts Of Ticks, Jonathan Graham Gerhart

Dissertations and Theses

Endosymbiosis in arthropods involves intracellular bacteria that supply an array of benefits to the host. Endosymbionts likely enhance the health of ticks by provisioning amino acids such as cysteine and tyrosine, and cofactors such as biotin and folic acid that are not available in blood--the sole nutrient source of ticks. Endosymbionts of ticks are of special interest due to their close evolutionary relationship with tick-vectored pathogens that impact livestock and human health. For example, ticks typically contain Coxiella-like endosymbionts (CLEs) that are the closest relatives of the human pathogen Coxiella burnetii. In order to understand the evolutionary relationship …

A Genetic And Biochemical Analysis Of Sulfolobus Spindle-Shaped Virus 1, Eric Alexander Iverson

Dissertations and Theses

Viruses infecting the Archaea exhibit a tremendous amount of morphological and genetic diversity. This is especially true for crenarchaeal viruses from the family Fuselloviridae, which possess spindle-shaped capsids and genomes that harbor a great number of uncharacterized genes. The functions of these unidentified gene products are of interest as they have the potential to provide valuable insights into the fusellovirus infection cycle and archaeal viruses in general. In an effort to better characterize the genetic requirements of the Fuselloviridae, we have performed genetic and biochemical experiments using the best studied fusellovirus, Sulfolobus spindle-shaped virus 1 (SSV1).

A comprehensive …

The Family Fuselloviridae : Diversity And Replication Of A Hyperthermic Virus Infecting The Archaeon Genus Sulfolobus, Adam Joseph Clore

Dissertations and Theses

The virus family Fuselloviridae infects the hyperthermophilic and acidophilic Crenarchaeon genus Sulfolobus and has been isolated from terrestrial hotsprings worldwide. Two previously uncharacterized Fuselloviruses, SSV-13 and SSV-L1, were isolated and sequenced and are compared to the five fully sequenced viruses presently in the public databases. Conserved promoters in all viruses and similar putative origins of replication suggest that these viruses use a transcriptional and genomic replication program similar to the relatively well-characterized SSV1. Pairwise comparisons of conserved genes in the seven virus genomes show that, like its host Sulfolobus, these viruses' genetic divergence correlates with geographic separation. Genome rearrangements, horizontal …