Biochemistry, Biophysics, and Structural Biology Commons^™

Molecular Mechanisms Of Amyloid-Like Fibril Formation, Sharareh Jalali

Dissertations

Proteins play a critical role in living systems by performing most of the functions inside cells. The latter is determined by the protein's three-dimensional structure when it is folded in its native state. However, under pathological conditions, proteins can misfold and aggregate, accounting for the formation of highly ordered insoluble assemblies known as amyloid fibrils. These assemblies are associated with diseases like Parkinson's and Alzheimer's. Strong evidence suggests that three mechanisms are critical for forming amyloid fibrils. These mechanisms are the nucleation of amyloid fibrils in solution (primary nucleation) as well as on the surface of existing fibrils (secondary nucleation) …

Exploring Topological Phonons In Different Length Scales: Microtubules And Acoustic Metamaterials, Ssu-Ying Chen

Dissertations

The topological concepts of electronic states have been extended to phononic systems, leading to the prediction of topological phonons in a variety of materials. These phonons play a crucial role in determining material properties such as thermal conductivity, thermoelectricity, superconductivity, and specific heat. The objective of this dissertation is to investigate the role of topological phonons at different length scales.

Firstly, the acoustic resonator properties of tubulin proteins, which form microtubules, will be explored The microtubule has been proposed as an analog of a topological phononic insulator due to its unique properties. One key characteristic of topological materials is the …

Continuum Modeling Of Active Nematics Via Data-Driven Equation Discovery, Connor Robertson

Dissertations

Data-driven modeling seeks to extract a parsimonious model for a physical system directly from measurement data. One of the most interpretable of these methods is Sparse Identification of Nonlinear Dynamics (SINDy), which selects a relatively sparse linear combination of model terms from a large set of (possibly nonlinear) candidates via optimization. This technique has shown promise for synthetic data generated by numerical simulations but the application of the techniques to real data is less developed. This dissertation applies SINDy to video data from a bio-inspired system of mictrotubule-motor protein assemblies, an example of nonequilibrium dynamics that has posed a significant …

Interactions Of Amyloid Peptides With Lipid Membranes, Yanxing Yang

Dissertations

The aggregation of amyloid proteins into fibrils is a hallmark of several diseases including Alzheimer’s (AD), Parkinson’s, and Type II diabetes. This aggregation process involves the formation of small size oligomers preceding the formation of insoluble fibrils. Recent studies have shown that these oligomers are more likely to be responsible for cell toxicity than fibrils. A possible mechanism of toxicity involves the interaction of oligomers with the cell membrane compromising its integrity. In particular, oligomers may form pore-like structures in the cell membrane affecting its permeability or they may induce lipid loss via a detergent-like effect. This dissertation aims to …

Reconstituting The Cyanobacterial Circadian Clock In Vitro, Pyong Hwa Kim

Dissertations

Cyanobacteria are photosynthetic organisms that are known to be responsible for oxygenating Earth’s early atmosphere. Having evolved to ensure optimal survival in the periodic light/dark cycle on this planet, their genetic codes are packed with various tools, including a sophisticated biological timekeeping system. Among the cyanobacteria is Synechococcus elongatus PCC 7942, the simplest clock-harboring organism with a powerful genetic tool that enabled the identification of its intricate timekeeping mechanism. The three central oscillator proteins—KaiA, KaiB, and KaiC—drive the 24 h cyclic gene expression rhythm of cyanobacteria, and the "ticking" of the oscillator can be reconstituted inside a test tube just …

Molecular Mechanism Of Cyanobacteria Circadian Clock Oscillator And Effect Of Co Factors On Its Oscillation, Manpreet Kaur

Dissertations

The circadian rhythms arise as an adaptation to the environmental 24-hour day and night cycle due to Earth's rotation. These rhythms prepare organisms to align their internal biological activities and day to day behavior or events with the environmental change of the 24-hour day and night cycle. Circadian rhythms are found widely in all living kingdoms of life on Earth. Cyanobacteria are photosynthetic prokaryotes which first used to study these circadian rhythms. Among cyanobacterial species, Synechococcus elongatus PCC 7942 (henceforth, S. Elongatus) is the simplest organism with a durable and sturdy circadian clock and is study as a model organism. …

1,4-Dioxane Biodegradation In Propanotrophs: Molecular Foundations And Implications For Environmental Remediation, Li Fei

Dissertations

1,4-Dioxane (dioxane) has emerged with an escalating concern given its human carcinogenicity and widespread occurrence in groundwater. Bioremediation is promising as an effective and cost-efficient treatment alternative for in situ or ex situ cleanup of dioxane and co-existing pollutants in the field. Soluble di-iron monooxygenases (SDIMOs) are reputed for their essential roles in initiating the cleavage of dioxane and other pollutants. In this doctoral dissertation, molecular foundations for SDIMOs-mediated dioxane biodegradation are untangled to promote the development and implication of site-specific bioremediation and natural attenuation strategies. This dissertation focused on propanotrophic bacteria given their pivotal roles in dioxane metabolism and …

Modeling Single Microtubules As A Colloidal System To Measure The Harmonic Interactions Between Tubulin Dimers In Bovine Brain Derived Versus Cancer Cell Derived Microtubules, Arooj Aslam

Dissertations

The local properties of tubulin dimers dictate the properties of the larger microtubule assembly. In order to elucidate this connection, tubulin-tubulin interactions are be modeled as harmonic interactions to map the stiffness matrix along the length of the microtubule. The strength of the interactions are measured by imaging and tracking the movement of segments along the microtubule over time, and then performing a fourier transform to extract the natural vibrational frequencies. Using this method the first ever reported experimental phonon spectrum of the microtubule is reported. This method can also be applied to other biological materials, and opens new doors …

Amyloid Proteins And Fibrils Stability, Farbod Mahmoudinobar

Dissertations

Compared to globular proteins that have a stable native structure, intrinsically disordered peptides (IDP) sample an ensemble of structures without folding into a native conformation.One example of IDP is the amyloid-beta(Abeta) protein which is the main constituent of senile plaques in the brain of Alzheimer's patients.Understanding the process by which IDPs undergo structural changes to form oligomers that eventually aggregate into senile plaques/amyloid fibrils may significantly advance the development of novel therapeutic methods to treat neurodegenerative diseases, for which there is no cure to date. This dissertation has two main objectives. The first one is to investigate and identify structural …

Engineering Of Escherichia Coli 2-Oxoglutarate Dehydrogenase Complex With Mechanistic And Synthetic Goals, Joydeep Chakraborty

Dissertations

The Escherichia coli 2-oxoglutarate dehydrogenase complex (OGDHc) compromises multiple copies of three enzymes - 2-oxoglutarate dehydrogenase (E1o), dihydrolipoyl succinyltransferase (E2o), and dihydrolipoyl dehydrogenase (E3). OGDHc is found in the Krebs cycle and catalyzes the formation of the all-important succinyl-Coenzyme A (succinyl-CoA). OGDHc was engineered to understand the catalytic mechanism and optimized for chemical synthetic goals.

Succinyl-CoA formation takes place within the catalytic domain of E2o via a transesterification reaction. The succinyl group from the thiol ester of S8-succinyldihydrolipoyl-E2o is transferred to the thiol group of CoA. Mechanistic studies were designed to investigate enzymatic transthioesterification. His375 and Asp374 was shown to …

Fluorescent Probes And Functionalized Nanoparticles For Bioimaging: Synthesis, Photophysical Properties And Applications, Xinglei Liu

Dissertations

The development of new organic molecular probes with excellent photophysical properties and high fluorescence quantum yields is of considerable interest to many research areas including one- and two-photon fluorescence microscopy, fluorescence-based sensing methodologies, and cancer therapy. Series of organic linear-/non-linear optical molecules including squaraine derivatives, and fluorene derivatives as well as other bioconjugates are designed and synthesized during the doctoral study for the aim of ion detection (Chapter 5), photo dynamic therapy, and deep-tissue imaging (Chapter 4). These optical probes are capable of absorbing light in the near infrared (NIR) window and thus have deeper penetration and cause less photodamage …