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Characterization of the Antibacterial Activity of the Type VI Secretion System
(2014-02-25)
This dissertation summarizes advances made toward understanding of the composition, structure, mechanism, and regulation of the bacterial type VI secretion system (T6SS). The T6SS is a widely conserved bacterial nanomachine ...
Mapping the Fitness Landscape of Gene Expression Uncovers the Cause of Antagonism and Sign Epistasis between Adaptive Mutations
(Public Library of Science, 2014)
How do adapting populations navigate the tensions between the costs of gene expression and the benefits of gene products to optimize the levels of many genes at once? Here we combined independently-arising beneficial ...
Loss and Recovery of Genetic Diversity in Adapting Populations of HIV
(Public Library of Science, 2014)
The evolution of drug resistance in HIV occurs by the fixation of specific, well-known, drug-resistance mutations, but the underlying population genetic processes are not well understood. By analyzing within-patient ...
Evolution after Introduction of a Novel Metabolic Pathway Consistently Leads to Restoration of Wild-Type Physiology
(Public Library of Science, 2013)
Organisms cope with physiological stressors through acclimatizing mechanisms in the short-term and adaptive mechanisms over evolutionary timescales. During adaptation to an environmental or genetic perturbation, beneficial ...
The Methanol Dehydrogenase Gene, mxaF, as a Functional and Phylogenetic Marker for Proteobacterial Methanotrophs in Natural Environments
(Public Library of Science, 2013)
The mxaF gene, coding for the large \((\alpha)\) subunit of methanol dehydrogenase, is highly conserved among distantly related methylotrophic species in the Alpha-, Beta- and Gammaproteobacteria. It is ubiquitous in ...
Investigating Synthetic Lethal Interactions with the Wall Teichoic Acid Pathway of Staphylococcus aureus
(2014-06-06)
The peptidoglycan of many Gram-positive bacteria is densely functionalized with anionic glycopolymers called wall teichoic acids (WTAs). Recent studies have shown that these polymers play crucial roles in cell shape ...
Evolutionarily Conserved Function of Huntingtin in Cellular Dynamics Related to Cell Adhesion and the Cytoskeleton
(2013-03-15)
Huntington's disease (HD) is a rare, dominantly inherited neurodegenerative disorder characterized by progressive chorea, emotional and behavioral disturbances, and cognitive decline. The single, causative mutation is an ...
Genetic Surveillance Detects Both Clonal and Epidemic Transmission of Malaria following Enhanced Intervention in Senegal
(Public Library of Science, 2013)
Using parasite genotyping tools, we screened patients with mild uncomplicated malaria seeking treatment at a clinic in Thiès, Senegal, from 2006 to 2011. We identified a growing frequency of infections caused by genetically ...
Development of an Optimized Medium, Strain and High-Throughput Culturing Methods for Methylobacterium extorquens
(Public Library of Science, 2013)
Methylobacterium extorquens strains are the best-studied methylotrophic model system, and their metabolism of single carbon compounds has been studied for over 50 years. Here we develop a new system for high-throughput ...
Bistability in Pseudomonas aeruginosa
(2013-10-08)
The opportunistic pathogen P. aeruginosa is a leading cause of hospital-accquired infections, and is also the primary cause of morbidity and mortality in patients with cystic fibrosis (CF). In this thesis, I describe the ...