Doctor of Philosophy

dissertationCopper zinc superoxide dismutase (Sod1) is a critical enzyme in limiting reactive oxygen species in both the cytosol and the mitochondrial inner membrane space. Sod1 dismutes superoxide anions to hydrogen peroxide and oxygen. The catalytic reaction is dependent on an active site copper ion and a disulfide-bonded conformation. The copper chaperone for superoxide dismutase (Ccs1) mediates the activation of Sod1 either through facilitated copper ion loading, disulfide bond formation or both. In the past several decades, Sod1 has been studied extensively due to frequent mutations found in the familial form of amyotrophic lateral sclerosis (ALS). To date, over 150 mutations have been characterized in Sod1; however, the basic maturation process of the enzyme is poorly understood. In this study, we explore the basic mechanism by which Sod1 matures. To define the activation process, we have performed extensive mutagenesis on the Cys residues in Ccs1. These mutations show a strict dependence on the CXC motif in domain 3, and the spacing of the two Cys residues. Mutations that alter the spacing or remove one of the cysteinyl residues from the CXC motif result in defects in copper metallation and disulfide oxidation. Mutations of the second Cys in the Ccs1 domain 3 or Cys146 of Sod1, which participates in the intramolecular disulfide, results in enhanced stalling of the heterdimeric complex between Ccs1 and Sod1 when affinity purification of Sod1 was performed. The two Sod1 cysteinyl residues exhibit differential phenotypes in copper loading. A C57S Sod1 mutant is catalytically dead and devoid of bound copper when purified from yeast. In contrast, a C146S mutant is partially copper loaded and exhibits weak Sod1 activity. C57S is proposed to serve as an entry site ligand during Cu(I) loading. In an attempt to observe an entry site Cu(I) site, X-ray absorption spectroscopy was performed on Sod1 and Ccs1 mutants that stall the heterodimer. The Cu(I) coordination site with thiolate ligands was observed. We believe that this entry site is functional, and that a single redox turnover of Cu(I) to Cu(II) is necessary to generate hydrogen peroxide. We characterize that through a reaction of hydrogen peroxide with a free thiol, cysteine146 of Sod1, a sulfenic acid intermediate is fomed. We propose that the sulfenic acid intermediate is able to undergo a nucleophilic attack, potential from a thiolate from the CXC motif in Ccs1, to promote a disulfide exchange reaction

A unification of the Holstein polaron and dynamic disorder pictures of charge transport in organic semiconductors

We present a unified and nonperturbative method for calculating spectral and transport properties of Hamiltonians with simultaneous Holstein (diagonal) and Peierls (off-diagonal) electron-phonon coupling. Our approach is motivated by the separation of energy scales in semiconducting organic molecular cystals, in which electrons couple to high-frequency intramolecular Holstein modes and to low-frequency intermolecular Peierls modes. We treat Peierls modes as quasi-classical dynamic disorder, while Holstein modes are included with a Lang-Firsov polaron transformation and no narrow-band approximation. Our method reduces to the popular polaron picture due to Holstein coupling and the dynamic disorder picture due to Peierls coupling. We derive an expression for efficient numerical evaluation of the frequency-resolved optical conductivity based on the Kubo formula and obtain the DC mobility from its zero-frequency component. We also use our method to calculate the electron-addition Green's function corresponding to the inverse photoemission spectrum. For realistic parameters, temperature-dependent DC mobility is largely determined by the Peierls-induced dynamic disorder with minor quantitative corrections due to polaronic band-narrowing, and an activated regime is not observed at relevant temperatures. In contrast, for frequency-resolved observables, a quantum mechanical treatment of the Holstein coupling is qualitatively important for capturing the phonon replica satellite structure.Comment: 12 pages, 7 figure

Panel: Restoring Grocery Access: The Vinton, Ohio

The village of McArthur sits in rural Vinton County in Southeast Ohio, with approximately 1,300 residents. In 2013, McArthur’s grocery store, the only grocery store in the county, was sold to Dollar General, which does not sell fresh food. As a result, residents had to travel more than 30 minutes from McArthur to another county to get fresh produce and groceries. McArthur also has a large population of seniors and others for whom access to transportation and to grocery stores is particularly limited. Launched in March of 2016, the Healthy Food for Ohio (HFFO) program, a Healthy Food Financing Initiative (HFFI), was able to attract and support a local grocer, Campbell’s Market, restoring the county with fresh food. The Campbell’s family has been in the grocery industry for more than 85 years and opened a 12,000 square foot store, adjacent to the local high school, in the winter of 2017. Campbell’s has hired over 30 employees from the local community and accepts SNAP and WIC food assistance benefits

Dynamics and spectroscopy of strongly coupled electrons and nuclei

This thesis describes work on several research topics in which transport and spectroscopy are influenced by strong electron-nuclear or nuclear-nuclear interactions. First, I give a broad overview of the motivations and background for the main topics covered in this thesis. In the next section, I explore the applicability of perturbative quantum master equations to linear absorption and nonlinear two-dimensional and pump-probe spectroscopies. Next, I introduce a theory of charge transport in organic semiconductors that unifies two popular pictures: incoherent polaron hopping and transient localization due to dynamic disorder. In the next section, I investigate the impact of phonon anharmonicity on the charge transport dynamics of soft semiconductors. Finally, I present a new method of efficiently calculating anharmonic vibrational spectra from ab initio molecular potential energy surfaces

The Connection, Volume 7, Issue 01, Fall 2010

The Connection is published by the Prevention Research Center (PRC), Prevention & Population Sciences, University of New Mexico, Albuquerque. The purpose of The Connection is to provide reports and updates on programs of the PRC and those of its Community Advisory Council and other partners.https://digitalrepository.unm.edu/hsc_prc_newsletters/1028/thumbnail.jp