Structural Biology Commons^™

Fire Fossils: Biomineral Infrastructures In Untangling Climates, Tanmayee More

Masters Theses

Diatoms drift, sediments sink, wildfires generate their own weather. Lightning strikes can blast sand into glass, and microscopic organisms do the same in the cold recesses of the ocean. What alchemies and metabolisms catalyze space, time, and energy? What are the thermodynamics of infrastructure in Climate Change?

Places, materials, and beings are afterimages. Through alchemical experiments, and multi-scalar imaging, I develop simulations of wildfires, and their profound, reverberating effects. In this thesis, a glass-meets-landscape experimental process enters these obscured conditions and renders new material relations for the built environment.

Fast 3d Printing Of Fine, Continuous, And Soft Fibers Via Embedded Solvent Exchange, Wonsik Eom, Mohammad Tanver Hossain, Vidush Parasramka, Jeongmin Kim, Ryan W. Y. Siu, Kate A. Sanders, Dakota Piorkowski, Andrew Lowe, Hyun Gi Koh, Michael F. L. De Volder, Douglas S. Fudge, Randy H. Ewoldt, Sameh H. Tawfick

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Nature uses fibrous structures for sensing and structural functions as observed in hairs, whiskers, stereocilia, spider silks, and hagfish slime thread skeins. Here, we demonstrate multi-nozzle printing of 3D hair arrays having freeform trajectories at a very high rate, with fiber diameters as fine as 1.5 µm, continuous lengths reaching tens of centimeters, and a wide range of materials with elastic moduli from 5 MPa to 3500 MPa. This is achieved via 3D printing by rapid solvent exchange in high yield stress micro granular gel, leading to radial solidification of the extruded polymer filament at a rate of 2.33 μm/s. …

Phagolysosomes Break Down The Membrane Of A Non-Apoptotic Corpse Independent Of Macroautophagy, Shruti Kolli, Cassidy J. Kline, Kimya M. Rad, Ann M. Wehman

Biological Sciences: Faculty Scholarship

Cell corpses must be cleared in an efficient manner to maintain tissue homeostasis and regulate immune responses. Ubiquitin-like Atg8/LC3 family proteins promote the degradation of membranes and internal cargo during both macroautophagy and corpse clearance, raising the question how macroautophagy contributes to corpse clearance. Studying the clearance of non-apoptotic dying polar bodies in Caenorhabditis elegans embryos, we show that the LC3 ortholog LGG-2 is enriched inside the polar body phagolysosome independent of autophagosome formation. We demonstrate that ATG-16.1 and ATG-16.2, which promote membrane association of lipidated Atg8/LC3 proteins, redundantly promote polar body membrane breakdown in phagolysosomes independent of their role …

Structural Characterization Of Cardiomyocyte Microenvironment In Murine Myocardium By Multimodal Stimulated Emission Depletion Microscopy, Zhao Zhang

All Dissertations

Cardiomyopathy, a disease of the heart muscle, is characterized by structural and functional abnormalities of the myocardium, in the absence of coronary artery disease, hypertension, valvular disease or congenital heart disease. In 2020, there were approximately 6.11 million prevalent cases of cardiomyopathy and myocarditis, and 0.37 million related deaths worldwide. Many affected individuals are asymptomatic, and chronically treated patients are at risk of heart failure. Within the myocardium, cardiomyocytes reside in a complex and dynamic extracellular matrix (ECM), consisting of basement membrane and interstitial matrix. The interactions between cardiomyocytes and myocardial ECM play a critical role in maintaining cardiac geometry …

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 …

A Pipeline To Generate Deep Learning Surrogates Of Genome-Scale Metabolic Models, Achilles Rasquinha

School of Computing: Dissertations, Theses, and Student Research

Genome-Scale Metabolic Models (GEMMs) are powerful reconstructions of biological systems that help metabolic engineers understand and predict growth conditions subjected to various environmental factors around the cellular metabolism of an organism in observation, purely in silico. Applications of metabolic engineering range from perturbation analysis and drug-target discovery to predicting growth rates of biotechnologically important metabolites and reaction objectives within dierent single-cell and multi-cellular organism types. GEMMs use mathematical frameworks for quantitative estimations of flux distributions within metabolic networks. The reasons behind why an organism activates, stuns, or fluctuates between alternative pathways for growth and survival, however, remain relatively unknown. GEMMs …

Challenges Of Constructing Entrainment Map For Arbitrary Circadian Models, Yuxuan (Nelson) Wu

Honors Theses

The entrainment map, developed by Dr.Diekman and Dr.Bose, is claimed to be a 1-dimensional map that produces a better prediction for phase-locking than methods than the phase response curve for circadian models. In his paper, he constructs the entrainment map for the two-dimensional circadian model, the Novak-Tyson model, and the other two higher-dimensional circadian models. For this thesis, we concentrate on exploring if it is viable to construct the entrainment map for other circadian models that are not included in his paper: the Becker-Weimann model and the Relogio model. In addition, we discuss the challenges of constructing the entrainment map …

Mimicking The Namib Desert Beetle With Hydrophilic And Hydrophobic Surfaces, Tyler Bracewell

Williams Honors College, Honors Research Projects

The Namib Desert beetle, Stenocara gracilipes, condenses fog that rolls in off the west coast of Namibia to provide itself with the water it needs for the day. By lifting its abdomen into the air to collect the water vapor, it condenses on hydrophilic bumps that are about 500μm in diameter and are spaced apart about 500-1500μm. Once the water reaches a critical size, the droplet rolls off the hydrophilic bump and onto the flat hydrophobic surface of the elytra. Since the beetle is angled with its abdomen in the air, the water rolls down to its mouth. A …

Histological Comparison Of Shark Dermis Across Various Ecomorphologies, Olivia Schuitema

UNF Graduate Theses and Dissertations

The integument plays essential roles in the structural support, protection, and hydrodynamic capability among fishes. Most shark skin research has been done on the external epidermal layer containing the dermal denticles, while the larger dermis layer has been mostly ignored. The dermis layer in sharks is composed of two layers, the upper stratum laxum and the lower stratum compactum, holding supportive collagen and elastin fibers. There may be morphological and compositional differences in the dermis layers across various species of sharks, although the extent of such is unknown. These potential differences may be represented by various dermal thicknesses and different …

Computational Analysis And Prediction Of Intrinsic Disorder And Intrinsic Disorder Functions In Proteins, Akila I. Katuwawala

Theses and Dissertations

COMPUTATIONAL ANALYSIS AND PREDICTION OF INTRINSIC DISORDER AND INTRINSIC DISORDER FUNCTIONS IN PROTEINS

By Akila Imesha Katuwawala

A dissertation submitted in partial fulfillment of the requirements for the degree of Engineering, Doctor of Philosophy with a concentration in Computer Science at Virginia Commonwealth University.

Virginia Commonwealth University, 2021

Director: Lukasz Kurgan, Professor, Department of Computer Science

Proteins, as a fundamental class of biomolecules, have been studied from various perspectives over the past two centuries. The traditional notion is that proteins require fixed and stable three-dimensional structures to carry out biological functions. However, there is mounting evidence regarding a “special” class …

Physicochemical Characterization, Structural Determination, And Molecular Dynamic Modeling Of Proso Millet Proteins For Enhanced Food Functionality, Felix Akharume

Theses and Dissertations--Biosystems and Agricultural Engineering

More than one-third of Americans today incorporate plant-based protein into their diet and about 40% believed that plant-based protein is healthier than animal protein, especially Millennials. The increasing global demand for plant-based proteins driven by the high cost of animal proteins, consumers’ desire for lean protein, vegetarianism, and the need for more sustainable green protein products have necessitated research into alternate emerging and underutilized sources of protein to complement or supplement the major plant protein in the market- soy, pea, and gluten. Therefore, this dissertation is focused on the valorization of the proteins in proso millet. Specifically, this work focused …

Characterization And Enzyme Engineering Of Laccases Towards Lignin Valorization In Aqueous Ionic Liquids, Joseph Stevens

Theses and Dissertations--Biosystems and Agricultural Engineering

Lignin is one of the most abundant polymers found in nature, making up 15 – 40% of the weight of terrestrial biomass. Due to the structural and monomeric heterogeneity of lignin, it is recalcitrant thermochemical and biological valorization methods. Converting lignin to value-added products via sustainable and cost-effective pathways will reduce waste and add value to future cellulosic biorefineries. Biological methods for lignin valorization (e.g. lignin degrading enzymes or microbes) is limited by low lignin solubility in biocompatible solvents, resulting in low product yield. Recent reports on biocatalysts for lignin valorization have focused on the lignolytic multicopper oxidase laccase, …

Influence Of Single And Multiple Histidine Residues And Their Ionization Properties On Transmembrane Helix Dynamics, Orientations And Fraying, Fahmida Afrose

Graduate Theses and Dissertations

Since aromatic and charged residues are often present in various locations of transmembrane helices of integral membrane proteins, their impacts on the molecular properties of transmembrane proteins and their interactions with lipids are of particular interest in many studies. In this work, I used solid-state deuterium NMR spectroscopy in designed model peptide GWALP23 [GGALW(LA)6LWLAGA] with selective deuterium labels to addresses the pH dependence and influence of single and multiple “guest” histidine residues in the orientation and dynamic behaviors of transmembrane proteins. The mutations include Gly to His (G2/22 to H2/22), Trp to His (W5/19 to H5/19) and Leu to His …

Development Of A Sonically Powered Biodegradable Nanogenerator For Bone Regeneration, Avi S. Patel

University Scholar Projects

Background: Reconstruction of bone fractures and defects remains a big challenge in orthopedic surgery. While regenerative engineering has advanced the field greatly using a combination of biomaterial scaffolds and stem cells, one matter of difficulty is inducing osteogenesis in these cells. Recent works have shown electricity’s ability to promote osteogenesis in stem cell lines when seeded in bone scaffolds; however, typical electrical stimulators are either (a) externally housed and require overcomplex percutaneous wires be connected to the implanted scaffold or (b) implanted non-degradable devices which contain toxic batteries and require invasive removal surgeries.

Objective: Here, we establish a biodegradable, piezoelectric …

Development Of A Sonically Powered Biodegradable Nanogenerator For Bone Regeneration, Avi Patel

Honors Scholar Theses

Background: Reconstruction of bone fractures and defects remains a big challenge in orthopedic surgery. While regenerative engineering has advanced the field greatly using a combination of biomaterial scaffolds and stem cells, one matter of difficulty is inducing osteogenesis in these cells. Recent works have shown electricity’s ability to promote osteogenesis in stem cell lines when seeded in bone scaffolds; however, typical electrical stimulators are either (a) externally housed and require overcomplex percutaneous wires be connected to the implanted scaffold or (b) implanted non-degradable devices which contain toxic batteries and require invasive removal surgeries.

Objective: Here, we establish a biodegradable, piezoelectric …

Incorporation Of Egfr And Ron Receptors Into Nanodiscs, Cristina Flores-Cadengo

Biomedical Engineering ETDs

Understanding the structure-function relationship of membrane receptors is essential to comprehend the crosstalk between key signaling pathways. Aberrant trans-activation between receptors can lead to tumorigenesis. Two of these receptors known to be involved in cancer development are receptor tyrosine kinases (RTKs), RON (Recepteur d'Origine Nantais) and EGFR (Epidermal Growth Factor Receptor). There has been evidence of heterodimerization and crosstalk between these two receptors based on co-immunoprecipitation, however the structural requirements behind these interactions remain unknown. Structural studies could provide insights into these RTKs’ modes of dimerization and structure-function relationship. However, structural studies of full-length membrane proteins are often difficult due …

Accurate Flexible Refinement Of Atomic Models Against Medium-Resolution Cryo-Em Maps Using Damped Dynamics, Julio A. Kovacs, Vitold E. Galkin, Willy Wriggers

Mechanical & Aerospace Engineering Faculty Publications

Background: Dramatic progress has recently been made in cryo-electron microscopy technologies, which now make possible the reconstruction of a growing number of biomolecular structures to near-atomic resolution. However, the need persists for fitting and refinement approaches that address those cases that require modeling assistance.

Methods: In this paper, we describe algorithms to optimize the performance of such medium-resolution refinement methods. These algorithms aim to automatically optimize the parameters that define the density shape of the flexibly fitted model, as well as the time-dependent damper cutoff distance. Atomic distance constraints can be prescribed for cases where extra containment of parts of …

Can A Comprehensive Transition Plan To Barefoot Running Be The Solution To The Injury Epidemic In American Endurance Runners?, Michael A. Scarlett

CMC Senior Theses

Fossils belonging to the genus Homo, dating as far back as two million years ago, exhibit uniquely efficient features suggesting that early humans had evolved to become exceptional endurance runners. Although they did not have the cushion or stability-control features provided in our modern day running shoes, our early human ancestors experienced far less of the running-related injuries we experience today. The injury rate has been estimated as high as 90% annually for Americans training for a marathon and as high as 79% annually for all American endurance runners. There is an injury epidemic in conventionally shod populations that …

Understanding Carbohydrate Recognition Mechanisms In Non-Catalytic Proteins Through Molecular Simulations, Abhishek A. Kognole

Theses and Dissertations--Chemical and Materials Engineering

Non-catalytic protein-carbohydrate interactions are an essential element of various biological events. This dissertation presents the work on understanding carbohydrate recognition mechanisms and their physical significance in two groups of non-catalytic proteins, also called lectins, which play key roles in major applications such as cellulosic biofuel production and drug delivery pathways. A computational approach using molecular modeling, molecular dynamic simulations and free energy calculations was used to study molecular-level protein-carbohydrate and protein-protein interactions. Various microorganisms like bacteria and fungi secret multi-modular enzymes to deconstruct cellulosic biomass into fermentable sugars. The carbohydrate binding modules (CBM) are non-catalytic domains of such enzymes that …

Investigation Of The Inherent Chemical, Structural, And Mechanical Attributes Of Bio-Engineered Composites Found In Nature: Alligator Gar’S Exoskeleton Fish Scales, Wayne Derald Hodo

Graduate Theses and Dissertations

The U.S. Army has determined a huge cost savings of up to 51% can be accomplished by reducing the gross vehicle weight, for their personnel carrier, by 33%. To cut cost, composite materials are needed. Man-made composites can have superior material properties (high-strength, high-fracture toughness, and lightweight), but they are prone to delamination at the glued-layered interface. In contrast, fish scale is a natural composite that has the same material properties and, additionally, tend not to delaminate.

The focus of this study was to learn how nature integrates hard and soft materials at each length scale to form a layered …

Incorporation Of Fibrin Into A Collagen–Glycosaminoglycan Matrix Results In A Scaffold With Improved Mechanical Properties And Enhanced Capacity To Resist Cell-Mediated Contraction, Claire Brougham, Tanya J. Levingstone, Stefan Jockenhoevel, Thomas C. Flanagan, Fergal J. O'Brien

Articles

Fibrin has many uses as a tissue engineering scaffold, however many in vivo studies have shown a reduction in function resulting from the susceptibility of fibrin to cell-mediated contraction. The overall aim of the present study was to develop and characterise a reinforced natural scaffold using fibrin, collagen and glycosaminoglycan (FCG), and to examine the cell-mediated contraction of this scaffold in comparison to fibrin gels. Through the use of an injection loading technique, a homogenous FCG scaffold was developed. Mechanical testing showed a sixfold increase in compressive modulus and a thirtyfold increase in tensile modulus of fibrin when reinforced with …

Viewing The Extracellular Matrix: An Imaging Method For Tissue Engineering, Michael Drakopoulos, Sarah Calve

The Summer Undergraduate Research Fellowship (SURF) Symposium

The field of regenerative medicine seeks to create replacement tissues and organs, both to repair deficiencies in biological function and to treat structural damage caused by injury. Scaffoldings mimicking extracellular matrix (ECM), the structure to which cells attach to form tissues, have been developed from synthetic polymers and also been prepared by decellularizing adult tissue. However, the structure of ECM undergoes significant remodeling during natural tissue repair, suggesting that ECM-replacement constructs that mirror developing tissues may promote better regeneration than those modeled on adult tissues. This work investigated the effectiveness of a method of viewing the extracellular matrix of developing …

Three-Dimensional Ideal Gas Reference State Based Energy Function, Avdesh Mishra

LSU New Orleans Theses and Dissertations

Energy functions are found to be a key of protein structure prediction. In this work, we propose a novel 3-dimensional energy function based on hydrophobic-hydrophilic properties of amino acid where we consider at least three different possible interaction of amino acid in a 3-dimensional sphere categorized as hydrophilic versus hydrophilic, hydrophobic versus hydrophobic and hydrophobic versus hydrophilic. Each of these interactions are governed by a 3-dimensional parameter alpha used to model the interaction and 3-dimensional parameter beta used to model weight of contribution. We use Genetic Algorithm (GA) to optimize the value of alpha, beta and Z-score. We obtain three …

Development Of Electron Microscopy Analysis And Simulation Tools For Nanohub, Mingxuan Lu, Chang Wan Han, Benjamin P. Haley, Volkan Ortalan

The Summer Undergraduate Research Fellowship (SURF) Symposium

Electron microscopy has a crucial role in the field of materials science and structural biology. Although electron microscopy gives lots of important results and findings, some additional simulations and image processing/reconstruction is required to get more information from the data that are collected from the experiments. For this purpose, researchers are using IMOD¹ and QSTEM² for electron microscopy analysis and simulation. IMOD is a set of programs used for tomographic reconstruction and 3D visualization and QSTEM is used for quantitative simulations of TEM and STEM images. However, IMOD and QSTEM are hard to install or use for beginners …

Complex Of Myoglobin With Phenol Bound In A Proximal Cavity, Xiao Huang, Chunxue Wang, Lesa R. Celeste, Leslie L. Lovelace, Shengfang Sun, John H. Dawson, Lukasz Lebioda

Faculty Publications

Sperm whale myoglobin (Mb) has weak dehaloperoxidase activity and catalyzes the peroxidative dehalogenation of 2,4,6-trichlorophenol (TCP) to 2,6-dichloroquinone. Crystals of Mb and of its more active G65T variant were used to study the binding of TCP, 4-iodophenol (4-IP) and phenol. The structures of crystals soaked overnight in a 10 mM solution of phenol revealed that a phenol molecule binds in the proximal cavity, forming a hydrogen bond to the hydroxyl of Tyr146 and hydrophobic contacts which include interactions with C and C of the proximal histidine His93. The phenol position corresponds to the strongest xenon binding site, Xe1. It …

Structural Basis Of Substrate Recognition In Thimet Oligopeptidase And Development Of Nanoparticles For Therapeutic Enzyme Delivery, Jonathan Mark Wagner

Theses and Dissertations--Molecular and Cellular Biochemistry

Neuropeptidases are responsible for degradation of signaling peptides in the central nervous system and periphery. Some neuropeptidases have also been shown to play a role as part of the cell’s hydrolytic machinery responsible for breaking down proteins and peptides into amino acids, and these enzymes therefore influence small peptide availability for antigen presentation. A better understanding of how neuropeptidases recognize their substrates could lead to therapeutics that modulate the activity of these important enzymes. Alternatively, re-engineering these enzymes to selectively hydrolyze undesirable peptides could make them attractive as therapeutics themselves. A key question in understanding the activity of these enzymes …

Impact Of Collateral Enlargement On Smooth Muscle Phenotype, Alexander Jerome Bynum

Master's Theses

Peripheral Artery Disease is a very serious disease characterized by an arterial occlusion due to atherosclerotic plaques. In response to an arterial occlusion, arteriogenesis occurs, causing smooth muscle cells to transition from a contractile to synthetic state. Also following an arterial occlusion, functional impairment was seen in the collateral circuit. An immunofluorescence protocol was developed in order to assess the impact of collateral enlargement (arteriogenesis) on smooth muscle phenotype at various time points. Smooth muscle α-actin was used to mark all smooth muscle cells, Ki-67 was used to label proliferating smooth muscle cells, and a fluorescent nuclear stain was used …