Life Sciences Commons^™

A Long-Term Neuroepigenomic Profile Of Prenatal Alcohol Exposure, Benjamin I. Laufer

Electronic Thesis and Dissertation Repository

Fetal Alcohol Spectrum Disorders (FASD) represent the largest preventable cause of cognitive deficits in the western world. The mechanism(s) of how prenatal alcohol exposure (PAE) results in FASD remain unknown. Towards this end, mouse models of PAE have successfully recreated endophenotypes that are characteristic of FASD. This doctoral thesis examines the long-term epigenomic alterations associated with PAE. I have examined both mice with PAE and human patients with FASD.

In the first set of experiments, mice with PAE and matched controls were raised to adulthood and then their whole brains were examined for alterations to gene expression, non-coding RNA (ncRNA) …

Ethanol Exposure During Synaptogenesis In A Mouse Model Of Fetal Alcohol Spectrum Disorders: Acute And Long-Term Effects On Gene Expression And Behaviour, Morgan L. Kleiber

Electronic Thesis and Dissertation Repository

Alcohol is a neuroactive molecule that is able to exert variable and often detrimental effects on the developing brain, resulting in a broad range of physiological, behavioural, and cognitive phenotypes that characterize ‘fetal alcohol spectrum disorders’ (FASD). Factors affecting the manifestation of these phenotypes include alcohol dosage, timing of exposure, and pattern of maternal alcohol consumption; however, the biological processes that are vulnerable to ethanol at any given neurodevelopmental stage are unclear, as is how their disruption results in the emergence of specific pathological phenotypes later in life.

The research included in this thesis utilizes a C57BL/6J (B6) mouse model …

The Intracellular Behaviour Of Burkholderia Cenocepacia In Murine Macrophages, Jennifer S. Tolman

Electronic Thesis and Dissertation Repository

Burkholderia cenocepacia is an opportunistic pathogen causing life-threatening infections in cystic fibrosis and other immunocompromised patients. The bacterium survives within macrophages by interfering with typical endocytic trafficking, resulting in delayed maturation of a B. cenocepacia-containing phagosome. We hypothesize that B. cenocepacia alters gene expression after internalization by macrophages, inducing genes involved in intracellular survival and host adaptation. Furthermore, we hypothesize that specialized bacterial secretion systems are involved in the interactions between intracellular bacteria and macrophages. In this work, we characterize later-stage infection of macrophages by B. cenocepacia, showing replication within an acidified endosomal compartment suggestive of a phagolysosome. …