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An Analysis Of The Interaction Between Sin3 And Methionine Metabolism In Drosophila, Mengying Liu

Wayne State University Dissertations

Chromatin modification and cellular metabolism are tightly connected. The mechanism for this cross-talk, however, remains incompletely understood. SIN3 controls histone acetylation through association with the histone deacetylase RPD3. In this study, my major goal is to explore the mechanism of how SIN3 regulates cellular metabolism.

Methionine metabolism generates the major methyl donor S-adenosylmethionine (SAM) for histone methylation. In collaboration with others, I report that reduced levels of some enzymes involved in methionine metabolism and histone demethylases lead to lethality, as well as wing development and cell proliferation defects in Drosophila melanogaster. Additionally, disruption of methionine metabolism can directly affect histone …

A Novel Role For Repetitive Sequences In Recognition Of The Drosophila Melanogaster X Chromosome, Sonal Suresh Joshi

Wayne State University Dissertations

In humans and fruit flies, males have one X chromosome while females have two. This imbalance in gene dosage is potentially lethal, and the process of dosage compensation corrects it. The MSL (Male Specific Lethal) complex, which is composed of five proteins and one of two functionally redundant long non-coding roX (RNA on the X) RNAs, brings about dosage compensation in Drosophila melanogaster. In fruit fly dosage compensation, all the genes on the single male X chromosome are upregulated approximately twofold, via chromatin modifications, to equalize gene dosage with the two X chromosomes of females. This process calls for highly …

Ecology Of Coyotes (Canis Latrans) In The Greater Detroit Area Of Southeastern Michigan, William B. Dodge

Wayne State University Dissertations

Coyote distribution and habitat use, diet and foraging behavior and space use patterns were investigated in the greater Detroit area of southeastern Michigan. We found evidence of coyotes on 24 of 30 (80%) suburban and 7 of 11 (64%) urban plots. Overall fifty-eight percent of coyote evidence was found within edge habitats, with den sites and tracks the only types of evidence found strictly in interior habitats. Land cover around evidence points included more wooded land cover than expected in suburban areas, suggesting the importance of tree cover for coyote occupancy, and more open space and wooded land cover than …

Analyzing Sumo-2/3 Modification In Regulation Of Breast Cancer Progression And Mitotic Chromosome Segregation, Divya Subramonian

Wayne State University Dissertations

Roles of SUMOylation in cancer metastasis and mitotic progression has been elucidated in this thesis. This vital and dynamic post-translational modification has been known to be dysregulated in several kinds of cancer. Global SUMO-2/3 conjugation is upregulated in a mouse metastatic breast cancer cell line, 66cl4, compared to a non-metastatic cell line 168FARN from the same genetic background. In order to identify the SUMO-2/3 substrates, SILAC labeled lysates from the two cell lines were immunopurified using SUMO-2/3 monoclonal antibodies. By using SUMO-2/3 epitope peptide elution (SUMO-2/3-ePIPE) and quantitative mass spectrometry, 66 SUMO-2/3 targets were identified, of which 15 targets are …

Genome Wide Analysis Identifies Sphingolipid Metabolism As A New Target Of Valproic Acid, Shyamalagauri Jadhav Jadhav

Wayne State University Dissertations

Bipolar disorder (BD), which is characterized by depression and mania, affects about 1% of the total world population. Current treatments are effective in only 40-60% of cases and cause severe side effects. Valproic acid (VPA), a branched short-chain fatty acid, is one of the most widely used drugs for the treatment of BD. Although many hypotheses have been postulated to explain the molecular mechanism of action of this drug in BD, the therapeutic mechanism is not understood. This knowledge gap has hampered the development of new drugs to treat this disorder. To identify candidate pathways affected by VPA, I performed …

Unraveling The Molecular Mechanisms Of Aposematic Pigmentation In Oncopeltus Fasciatus, Jin Liu

Wayne State University Dissertations

Insects display the extraordinary amount of morphological variation, particularly in regard to their colorations. This diversity in coloration exists both in terms of the array of colors as well as the patterning of pigments. Previous studies have revealed that melanin, ommochrome, and pteridine are the most common pigments constituting insect color patterns. Among these three, the melanin pathway has been best studied so far and presents the foundation of the current understanding of insect coloration. At the same time, though, most of this insight relied on work performed in model systems such as Drosophila and Tribolium, which have significant limitations …

Imaging Anti-Proliferative Compounds With Flt-Pet, Christopher Mchugh

Wayne State University Dissertations

Imaging is critical in the detection and management of malignancies, and positron emission tomography (PET) is an imaging approach that provides information regarding cancer physiology through the tracking of molecular pathways and receptors. 3’-fluoro-3’-deoxythymidine (FLT) is a PET tracer designed to image cellular proliferation, which is a hallmark of cancer. FLT has been used to study the response of cancer to a variety of treatments such as chemotherapy, targeted agents, and radiation.

Here we explored FLT retention as a biomarker to monitor the anti-proliferative effect of the synthetic glucocorticoid (GC) dexamethasone (Dex) on non-small cell lung cancer (NSCLC). The basis …

Role Of Secretory Granule Heterogeneity In Calcium-Triggered Exocytosis, Tejeshwar Rao

Wayne State University Dissertations

The sympathetic nervous system is activated by a variety of threats to organismal homeostasis. The adrenomedullary chromaffin cell is the core effector of sympathetic activity in the peripheral nervous system. By design, the chromaffin cell secretory response is mutable so that release can be rapidly tuned to drive context-dependent changes in physiological function. However, the mechanisms by which this tuning is achieved with such high temporal fidelity and context specificity remain unclear. This represents a major gap in our understanding of the sympatho-adrenal system since it is known to modify the function of nearly every organ system in the body. …

Cardiolipin Is Required For Optimal Acetyl-Coa Metabolism, Vaishnavi Raja

Wayne State University Dissertations

The phospholipid cardiolipin (CL) is crucial for many cellular functions and signaling pathways, both inside and outside of mitochondria. My thesis focuses on the role of CL in energy metabolism. Many reactions of electron transport and oxidative phosphorylation, the transport of metabolites needed for these processes, and the stabilization of electron transport chain supercomplexes, require CL. Recent studies indicate that CL is required for the synthesis of iron-sulfur (Fe-S) co-factors, which are essential for numerous metabolic pathways. Activation of carnitine-acetylcarnitine translocase, which transports acetyl-CoA into the mitochondria, is CL dependent. The presence of substantial amounts of CL in the peroxisomal …