Investigations of potential roles of hypoxic response genes in Drosophila primordial germ cell development

The cellular responses that allow a cell to survive and adapt to hypoxic stress (low oxygen) are largely conserved. The Hypoxia-Inducible Factor transcription factors (HIFs) are the primary transcription factors mediating responses to hypoxic stress. HIFs are composed of alpha and beta subunits. HIF-α is only stable in hypoxic conditions. The pathway for oxygen-dependent degradation of HIF-α includes a prolyl-hydroxylase (PHD) and the VHL E3 ligase. The Drosophila homlogs of HIF-α, HIF-β, PHD, and VHL are encoded by the similar, tango, fatiga/Hph, and Vhl genes, respectively. Previous studies have demonstrated that similar has roles in Drosophila tracheal development as well as border cell migration. Here I have used the development of germ cells in Drosophila as a tool to study the effects of low oxygen stress, and to explore the potential roles of hypoxic response genes in germ cell development. Utilizing low oxygen culture conditions and loss-of-function mutants I have observed that Drosophila embryogenesis is sensitive to oxygen tension and the zygotic loss of Drosophila HIF-1α is not sufficient to induce primordial germ cell defects. Further examination of the complete loss-of-function of other Drosophila HIF components, such as fatiga, could reveal whether it is the HIF hypoxic response pathway or a HIF independent hypoxia induced pathway that mediates Drosophila primordial germ cell development in wild-type embryos exposed to hypoxic conditions

Results from Iowa State Female Graduate Student Needs Assessment Survey, July 2012

During the spring 2012 semester, a task force of graduate students, staff, and faculty created a survey to gather information from women graduate students about their experiences at Iowa State University (ISU). The survey was adapted from similar surveys at MIT and University of Maryland. Our survey had four main sections: (1) Campus climate, (2) Professional development and academic services, (3) Student workload and student services, (4) Wellness, family and housing

Harnessing peripheral DNA methylation differences in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to reveal novel biomarkers of disease

Background Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease impacting an estimated 44 million adults worldwide. The causal pathology of AD (accumulation of amyloid-beta and tau), precedes hallmark symptoms of dementia by more than a decade, necessitating development of early diagnostic markers of disease onset, particularly for new drugs that aim to modify disease processes. To evaluate differentially methylated positions (DMPs) as novel blood-based biomarkers of AD, we used a subset of 653 individuals with peripheral blood (PB) samples in the Alzheimer’s disease Neuroimaging Initiative (ADNI) consortium. The selected cohort of AD, mild cognitive impairment (MCI), and age-matched healthy controls (CN) all had imaging, genetics, transcriptomics, cerebrospinal protein markers, and comprehensive clinical records, providing a rich resource of concurrent multi-omics and phenotypic information on a well-phenotyped subset of ADNI participants. Results In this manuscript, we report cross-diagnosis differential peripheral DNA methylation in a cohort of AD, MCI, and age-matched CN individuals with longitudinal DNA methylation measurements. Epigenome-wide association studies (EWAS) were performed using a mixed model with repeated measures over time with a P value cutoff of 1 × 10−5 to test contrasts of pairwise differential peripheral methylation in AD vs CN, AD vs MCI, and MCI vs CN. The most highly significant differentially methylated loci also tracked with Mini Mental State Examination (MMSE) scores. Differentially methylated loci were enriched near brain and neurodegeneration-related genes (e.g., BDNF, BIN1, APOC1) validated using the genotype tissue expression project portal (GTex). Conclusions Our work shows that peripheral differential methylation between age-matched subjects with AD relative to healthy controls will provide opportunities to further investigate and validate differential methylation as a surrogate of disease. Given the inaccessibility of brain tissue, the PB-associated methylation marks may help identify the stage of disease and progression phenotype, information that would be central to bringing forward successful drugs for AD

Investigations of potential roles of hypoxic response genes in Drosophila primordial germ cell development

The cellular responses that allow a cell to survive and adapt to hypoxic stress (low oxygen) are largely conserved. The Hypoxia-Inducible Factor transcription factors (HIFs) are the primary transcription factors mediating responses to hypoxic stress. HIFs are composed of alpha and beta subunits. HIF-α is only stable in hypoxic conditions. The pathway for oxygen-dependent degradation of HIF-α includes a prolyl-hydroxylase (PHD) and the VHL E3 ligase. The Drosophila homlogs of HIF-α, HIF-β, PHD, and VHL are encoded by the similar, tango, fatiga/Hph, and Vhl genes, respectively. Previous studies have demonstrated that similar has roles in Drosophila tracheal development as well as border cell migration. Here I have used the development of germ cells in Drosophila as a tool to study the effects of low oxygen stress, and to explore the potential roles of hypoxic response genes in germ cell development. Utilizing low oxygen culture conditions and loss-of-function mutants I have observed that Drosophila embryogenesis is sensitive to oxygen tension and the zygotic loss of Drosophila HIF-1α is not sufficient to induce primordial germ cell defects. Further examination of the complete loss-of-function of other Drosophila HIF components, such as fatiga, could reveal whether it is the HIF hypoxic response pathway or a HIF independent hypoxia induced pathway that mediates Drosophila primordial germ cell development in wild-type embryos exposed to hypoxic conditions.</p

Investigations of potential roles of hypoxic response genes in Drosophila primordial germ cell development

The cellular responses that allow a cell to survive and adapt to hypoxic stress (low oxygen) are largely conserved. The Hypoxia-Inducible Factor transcription factors (HIFs) are the primary transcription factors mediating responses to hypoxic stress. HIFs are composed of alpha and beta subunits. HIF-α is only stable in hypoxic conditions. The pathway for oxygen-dependent degradation of HIF-α includes a prolyl-hydroxylase (PHD) and the VHL E3 ligase. The Drosophila homlogs of HIF-α, HIF-β, PHD, and VHL are encoded by the similar, tango, fatiga/Hph, and Vhl genes, respectively. Previous studies have demonstrated that similar has roles in Drosophila tracheal development as well as border cell migration. Here I have used the development of germ cells in Drosophila as a tool to study the effects of low oxygen stress, and to explore the potential roles of hypoxic response genes in germ cell development. Utilizing low oxygen culture conditions and loss-of-function mutants I have observed that Drosophila embryogenesis is sensitive to oxygen tension and the zygotic loss of Drosophila HIF-1α is not sufficient to induce primordial germ cell defects. Further examination of the complete loss-of-function of other Drosophila HIF components, such as fatiga, could reveal whether it is the HIF hypoxic response pathway or a HIF independent hypoxia induced pathway that mediates Drosophila primordial germ cell development in wild-type embryos exposed to hypoxic conditions

Results from Iowa State Female Graduate Student Needs Assessment Survey, July 2012

During the spring 2012 semester, a task force of graduate students, staff, and faculty created a survey to gather information from women graduate students about their experiences at Iowa State University (ISU). The survey was adapted from similar surveys at MIT and University of Maryland. Our survey had four main sections: (1) Campus climate, (2) Professional development and academic services, (3) Student workload and student services, (4) Wellness, family and housing.</p