Life Sciences Commons^™

Methods To Identify And Develop Drugs For Cryptosporidiosis, Rajiv Satish Jumani

Graduate College Dissertations and Theses

Cryptosporidiosis is a common diarrheal disease caused by intestinal infection with the apicomplexan parasite Cryptosporidium, in humans usually either with C. hominis or C. parvum. Unfortunately, given a large burden of disease in children and immunocompromised people like AIDS patients, the only currently approved treatment, nitazoxanide, is unreliable for these patient populations. To address the urgent need for new drugs for the most vulnerable populations, large phenotypic screening efforts have been established to identify anti-Cryptosporidium growth inhibitors in vitro (hits). However, in the absence of a gold standard drug, the in vitro and in vivo characteristics that should be used …

An Analysis Of Between-Cow Variation In Innate Immunity In Relation To Mastitis Severity, Filiz Korkmaz

Graduate College Dissertations and Theses

Bovine mastitis remains one of the costliest diseases affecting the dairy industry. Individual susceptibility to mastitis and severity of infection varies between animals and can only be partially explained by genetics. As such, understanding how genetic predisposition coordinately interacts with epigenetic modifications and environmental exposures is necessary to bridge the gap in missing heritability. The role of DNA methylation in regulating the response to bacterial lipopolysaccharide (LPS) was first determined by performing reduced representation bisulfite sequencing on fibroblasts isolated from heifers at 5- and 16-months of age that exhibit an age-dependent up-regulation in LPS-responsiveness. More than 14,000 differentially methylated sites …

Characterizing The Role And Regulation Of Glycogen Metabolism In Dendritic Cell Immune Responses, Phyu Myat Thwe

Graduate College Dissertations and Theses

Dendritic cells (DCs) are the most potent professional antigen presenting cells (pAPCs) of the immune system and play a fundamental role in coordinating innate and adaptive immune responses. Through the expression of a wide array of pattern recognition receptors (PRRs), such as toll-like receptors (TLRs), DCs recognize a variety of microbial pathogens and infectious stimuli. Stimulation of DCs through TLR ligation results in a rapid series of activation-associated events, termed "maturation," which include the upregulation of surface co-stimulatory molecule expression, inflammatory cytokine secretion, and stimulation of naïve T cells via antigen presentation by MHC molecules.

Activation of DCs through TLRs …

Methylation Controlled J Protein Is A Master Regulator Of Mitochondrial Metabolism, Devin Pierre Champagne

Graduate College Dissertations and Theses

Methylation controlled J protein (MCJ) is a negative regulator of mitochondrial metabolism that has a substantial impact on overall cell metabolism and function. MCJ is highly expressed by naïve CD8+ T cells, however its role in their immune effector functions was unknown. In this dissertation, it will be demonstrated that MCJ restricts the mitochondrial metabolism of CD8+ T cells, in part by reducing respiratory supercomplex formation. MCJ deficiency enhances the immune effector functions and memory responses of CD8+ T cells in a mitochondrial ATP dependent manner. As a consequence, protection to influenza virus infection is substantially improved. Reduced expression of …

Altered Gastrointestinal Motility In Multiple Sclerosis, Estelle Trego Spear

Graduate College Dissertations and Theses

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that causes motor, visual, and sensory symptoms. Patients also experience constipation, which is not yet understood, but could involve dysfunction of the enteric nervous system (ENS). Autoimmune targeting of the ENS occurs in other autoimmune diseases that exhibit gastrointestinal (GI) symptoms, and similar mechanisms could lead to GI dysfunction in MS. Here, we characterize GI dysmotility in the experimental autoimmune encephalomyelitis (EAE) model of MS and test whether autoantibodies targeting the ENS are present in the serum of MS patients.

Male SJL or B6 mice were induced with …

Uncovering The Variable Life History Traits And Strategies Of The Gregarine Parasite, Monocystis Perplexa, In Its Invasive Earthworm Host, Amynthas Agrestis, Erin L. Keller

Graduate College Dissertations and Theses

Parasite life histories influence many aspects of infection dynamics, from the parasite infrapopulation diversity to the fitness of the parasite (the number of successfully transmitted parasites). Studies of medically important parasites, such as the parasite responsible for malaria (Plasmodium spp.), demonstrate the usefulness of investigating the life histories of parasites to better understand infection characteristics such as parasite load and probability of transmission.

The gregarines are a diverse group of apicomplexan parasites that infect invertebrates, and are particularly common in insects and annelids. Given the great biodiversity and importance of their hosts, coupled with their close evolutionary relationship with important …