Molecular Biology Commons^™

Quantitative Imaging Of Tensile Forces At Cell-Cell Junction With Dna-Based Probes, Puspam Keshri

Doctoral Dissertations

Mechanical forces are an integral part in biology, they regulate several cellular properties, such as morphology, proliferation, migration. These forces are also involved in receptor signaling and the differentiation of different cell types. Different proteins and biomolecules such as cadherin, integrin, notch proteins are essential elements of these processes. Measuring these intercellular forces are challenging considering the minimal intensity (piconewton-level) of these molecular forces. In our lab, we have developed a membrane DNA tension probe (MDTP) that uses a DNA hairpin module to sense tensile forces and has a lipid anchor to modify onto live-cell membranes. The programmability of DNA …

Characterization Of Biodistribution Of Transferrin And Receptor Binding Mechanism By Mass Spectrometry, Hanwei Zhao

Doctoral Dissertations

Protein-based therapeutics have emerged as a key driver of rapid growth in drug development pipelines. However, developing such protein drugs is not straightforward in most cases, the existence of physiological barriers greatly restricts the efficient delivery of many therapeutic molecules, and therefore limits their clinical applications. A promising way to address this challenge takes advantage of certain transport protein which can effectively across and enhance the permeability of these barriers, such as transferrin (Tf) which can be internalized by malignant cells and cross physiological barriers via transferrin receptor (TfR)-mediated endocytosis and transcytosis. However, developing such products is impossible without successfully …

The Molecular Basis Of Caspase-9 Inactivation By Pka And C-Abl Kinases, Banyuhay Paningbatan Serrano

Doctoral Dissertations

Caspases are the cysteine proteases that facilitate the fundamental pathway of programmed cell death or apoptosis. The activation and function of these powerful enzymes are tightly regulated to ensure the faithful execution of apoptosis and prevent untimely cell death. Many deadly human diseases such as cancer, neurodegeneration and autoimmune disorders have been associated with defective activation and faulty regulation of caspases. As such, caspases are considered as attractive drug targets, which when properly controlled, can lead to effective therapeutics for apoptosis-related diseases. Thus, comprehensive investigations of the structure, function and regulation of caspases are necessary to understand the complex mechanisms …

Photolysis Of Triazenylbenzoic Acids For Click Chemistry, Adam Gann

Doctoral Dissertations

Copper catalyzed cycloaddition of terminal alkynes and azides has revolutionized the field of bioconjugate chemistry. Unfortunately, typical copper catalysts are known to disrupt relevant biological systems, so it has become necessary to develop new, copper-free methods that are less cytotoxic. particular interest are "click" probes which can be activated with an outside light source, giving the user spatial and temporal control over the system being investigated. We have developed a method in which an aryl diazonium salt is rapidly generated using photolysis of the triazene functional group, and subsequently coupled with an electron rich aromatic nucleophile to yield an azobenzene. …

Application Of Computational Molecular Biophysics To Problems In Bacterial Chemotaxis, Davi Ortega

Doctoral Dissertations

The combination of physics, biology, chemistry, and computer science constitutes the promising field of computational molecular biophysics. This field studies the molecular properties of DNA, protein lipids and biomolecules using computational methods. For this dissertation, I approached four problems involving the chemotaxis pathway, the set of proteins that function as the navigation system of bacteria and lower eukaryotes.

In the first chapter, I used a special-purpose machine for molecular dynamics simulations, Anton, to simulate the signaling domain of the chemoreceptor in different signaling states for a total of 6 microseconds. Among other findings, this study provides enough evidence to propose …

A Time-And-Space Parallelized Algorithm For The Cable Equation, Chuan Li

Doctoral Dissertations

Electrical propagation in excitable tissue, such as nerve fibers and heart muscle, is described by a nonlinear diffusion-reaction parabolic partial differential equation for the transmembrane voltage $V(x,t)$, known as the cable equation. This equation involves a highly nonlinear source term, representing the total ionic current across the membrane, governed by a Hodgkin-Huxley type ionic model, and requires the solution of a system of ordinary differential equations. Thus, the model consists of a PDE (in 1-, 2- or 3-dimensions) coupled to a system of ODEs, and it is very expensive to solve, especially in 2 and 3 dimensions.

In order to …

Human Decomposition Ecology At The University Of Tennessee Anthropology Research Facility, Franklin Edward Damann

Doctoral Dissertations

The University of Tennessee Anthropology Research Facility (ARF) is well known for its unique history as a site of human decomposition research in a natural environment. It has been integral to our understanding of the processes of human decomposition. Over the last 30 years 1,089 bodies have decomposed at this 1.28 acre facility, producing a density of 850 corpses per acre of land. This project evaluated the abiotic and biotic characteristics of the soil exposed to various levels of human decomposition in order to determine the effect on the physicochemical properties and the indigenous bacterial communities.

Specifically, 75 soil samples …