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Isoform-Specific Roles Of Extracellular Signal-Regulated Kinases In Pain, Benedict Alter
Isoform-Specific Roles Of Extracellular Signal-Regulated Kinases In Pain, Benedict Alter
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ABSTRACT OF THE DISSERTATION Isoform-specific roles of Extracellular Signal-Regulated Kinases in pain by Benedict Joseph Alter Doctor of Philosophy in Biology and Biomedical Sciences Neurosciences Washington University in St. Louis, 2012 Professor Robert Gereau, Chairperson The extracellular signal-regulated kinase: ERK) isoforms, ERK1 and ERK2, are believed to be key signaling molecules in nociception and nociceptive sensitization. Studies utilizing inhibitors targeting the shared ERK1/2 upstream activator, mitogen-activated protein kinase kinase: MEK), and transgenic mice expressing a dominant negative form of MEK have established the importance of ERK1/2 signaling. However, these techniques do not discriminate between ERK1 and ERK2. To dissect the …
From Bacteria To Human: Biophysical Studies Of Inward Rectifying Potassium Channels, Wayland Cheng
From Bacteria To Human: Biophysical Studies Of Inward Rectifying Potassium Channels, Wayland Cheng
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Inward rectifying potassium: Kir) channels are important in regulating cellular excitability in organs such as the heart, brain and pancreas. Prokaryotic KirBac channels are structurally similar to eukaryotic Kir channels, but distantly related and of unknown function. The goal of this thesis has been to investigate the functional properties of KirBac1.1 and to relate these findings to eukaryotic Kir channels. The approach was to use recombinantly-expressed, purified K+ channels--KirBac1.1, KcsA, Kir2.1 and Kir2.2--in order to integrate findings from functional studies, using liposomal flux assays and patch-clamping, with high-resolution crystal structures. By reconstituting KirBac1.1 into giant liposomes for patch-clamping, I show …
Joint Functions Of Mett-10 And Dynein In The Caenorhabditis Elegans Germ Line, Maia Dorsett
Joint Functions Of Mett-10 And Dynein In The Caenorhabditis Elegans Germ Line, Maia Dorsett
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During normal development as well as in diseased states such as cancer, extracellular "niches" often provide cues to proximal cells and activate intracellular pathways. Activation of such signaling pathways in turn instructs cellular proliferation and differentiation. In the C.elegans gonad, GLP-1/Notch signaling instructs germ line stem cells to self renew through mitotic cell division. As germ cells progressively move out of the niche, they differentiate by entering meiosis and eventually form gametes. Using this model system, I uncovered a cooperative role for the METT-10 putative methyltransferase and the dynein motor complex in regulating the balance between germ cell proliferation and …
Atm Deficiency -- A Multifaceted Defect In Lymphocyte Development, Beth Helmink
Atm Deficiency -- A Multifaceted Defect In Lymphocyte Development, Beth Helmink
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The generation of a functional antigen receptor gene in developing lymphocytes requires that the second exon be assembled through a process known as V(D)J recombination, a process that necessarily involves the generation and repair of DNA double-strand breaks made by the Rag endonuclease. Double strand breaks incurred during G1 of the cell cycle activate ATM, a PI3-kinase-like kinase that, in response to genotoxic DNA damage, is known to phosphorylate hundreds of proteins with unique and diverse functions. Notably, deficiencies in ATM lead to ataxia-telangiectasia, a syndrome characterized by lymphopenia, genomic instability and a predisposition to tumors involving antigen receptor loci …
The Role Of Autophagy And Il-17 In Bone Resorption, Carl Deselm
The Role Of Autophagy And Il-17 In Bone Resorption, Carl Deselm
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Osteoclasts are essential for skeletal homeostasis: Teitelbaum, 2000). These macrophage-lineage cells function by generating a polarized microenvironment between themselves and bone wherein skeletal matrix is degraded. This resorptive compartment is isolated from the general extracellular space by an actin ring which encompasses the ruffled border, a convoluted plasma membrane structure formed by its fusion with lysosome-related vesicles containing an electrogenic H+ATPase, a chloride channel, LAMP-1, and cathepsin K. In consequence, resorption of bone reflects secretion of HCl to mobilize mineral, and cathepsin K to degrade the collagen-rich organic matrix, into the resorptive space: Stenbeck, 2002; Zhao et al., 2008). We …