Physical Sciences and Mathematics Commons^™

Don't Sell Them Short, There's More To Bacterial Natural Products Than Antibiotics, Alison Clare Domzalski

Dissertations, Theses, and Capstone Projects

Recent genomic studies of microbiomes have revealed an overwhelming number of biosynthetic genes of unknown function. Most of these “cryptic” biosynthetic genes are not expressed in laboratory monocultures of individual microbes. Thus, there remains tremendous untapped potential for natural products discovery. Here we employ mixed microbial culture (MMC) as a simple yet powerful approach to awaken cryptic biosynthetic gene clusters. Our preliminary studies demonstrated that arrays of metabolites could be induced in MMCs upon environmental cues, such as surface adhesion. Using this system, we have screened, identified, and isolated bioactive bacterial metabolites, which were characterized structurally and biologically. Of the …

Tools And Strategies For The Patterning Of Bioactive Molecules And Macromolecules, Daniel J. Valles

Dissertations, Theses, and Capstone Projects

Hypersurface Photolithography (HP) is a printing method for fabricating structures and patterns composed of soft materials bound to solid surfaces and with ~1 micrometer resolution in the x, y, and z dimensions. This platform leverages benign, low intensity light to perform photochemical surface reactions with spatial and temporal control of irradiation, and, as a result, is particularly useful for patterning delicate organic and biological material. In particular, surface- initiated controlled radical polymerizations can be leveraged to create arbitrary polymer and block- copolymer brush patterns. Chapter 1 will review the advances in instrumentation architectures from our group that have made these …

Connecting Communities To Coastal Resilience: Enhancing Sustainability Through Public Participation In Salt Marsh Management And Restoration In Suffolk County, Ny, Jennifer L. Mcgivern

Dissertations, Theses, and Capstone Projects

Coastal resiliency is becoming significantly more critical to the livelihood of coastal communities as the frequency and intensity of storm events increases and is exacerbated by rising sea levels due to climate change. In October 2012 Superstorm Sandy impacted the New York-New Jersey area costing over $70 billion in storm damages and 147 lives lost, as storm surges surpassed record highs for the region. Protruding more than 100 miles into the Atlantic Ocean with over 1,000 miles of shoreline, Long Island is particularly vulnerable to the increasingly ferocious and numerous storms as well as the rising sea levels that climate …

Molecular Dynamics Simulations Of Self-Assemblies In Nature And Nanotechnology, Phu Khanh Tang

Dissertations, Theses, and Capstone Projects

Nature usually divides complex systems into smaller building blocks specializing in a few tasks since one entity cannot achieve everything. Therefore, self-assembly is a robust tool exploited by Nature to build hierarchical systems that accomplish unique functions. The cell membrane distinguishes itself as an example of Nature’s self-assembly, defining and protecting the cell. By mimicking Nature’s designs using synthetically designed self-assemblies, researchers with advanced nanotechnological comprehension can manipulate these synthetic self-assemblies to improve many aspects of modern medicine and materials science. Understanding the competing underlying molecular interactions in self-assembly is always of interest to the academic scientific community and industry. …

Computational Modeling Of Water And Proteins In Drug Discovery, Anthony Cruz Balberdy

Dissertations, Theses, and Capstone Projects

This thesis aims to improve how structural and thermodynamic properties of water on protein surfaces can be exploited to aid early stage drug discovery and lead optimization. We first discuss our development of SSTMap, a public domain software suite that maps out the properties of water on biomolecular surfaces. We then show the utility of these maps in describing differences in binding affinities between congeneric pairs of ligands. We then discuss our use of solvation maps in the prospective discovery of novel binders to cytochrome C peroxidase. Finally, we present our creation and validation of a homology model of Interleukin-24 …

Design, Synthesis And Evaluation Of Molecules With Selective And Poly-Pharmacological Actions At D1r, D3r And Sigma Receptors, Pierpaolo Cordone

Dissertations, Theses, and Capstone Projects

The dopamine D3 receptor (D3R) is one of the most studied receptors involved in drug addiction. One of the most common strategies to treat substance use disorders is via D3R antagonism. The majority of the D3R antagonists synthesized so far have poor pharmacokinetic properties and/or lack selectivity toward D3R. In this thesis, the design, synthesis and biological evaluation of novel molecules that target the dopamine D1 receptor (D1R), D3R and the serendipitous discovery of molecules that target s receptors will be described.

Chapter 1 presents a survey of the fundamental pharmacology of D1R, D3R and s receptors and the therapeutic …

Third Harmonic Generation: A Method For Visualizing Myelin In The Murine Cerebral Cortex, Michael Redlich

Dissertations, Theses, and Capstone Projects

Here we present the use of Third Harmonic Generation (THG) for the label-free imaging of myelinated axons in the murine cerebral cortex. Myelin plays an important role in the processes of learning and disease. However, much of the myelin biology research thus far has focused on white matter tracts where myelin is more visible. Much is still unknown, particularly with regard to myelin in gray matter. First, we engage in THG microscopy using an optical parametric oscillator pumped by a titanium-sapphire laser to demonstrate the utility of the technique for imaging myelin in vivo. Second, we investigate the use of …

The C. Neoformans Cell Wall: A Scaffold For Virulence, Christine Chrissian

Dissertations, Theses, and Capstone Projects

Cryptococcus neoformans is a globally distributed opportunistic fungal pathogen and the causative agent of life threatening cryptococcal meningoencephalitis in immunocompromised individuals, resulting in ~180,000 deaths each year worldwide. A primary virulence-associated trait of this organism is the production of melanin. Melanins are a class of diverse pigments produced via the oxidation and polymerization of aromatic ring compounds that have a characteristically complex, heterogenous, and amorphous structure. They are synthesized by representatives of all biological kingdoms and share a multitude of remarkable properties such as the ability to absorb ultraviolet (UV) light and protect against ionizing radiation. Melanin production in fungi …

Using The Marcus Inverted Region And Artificial Cofactors To Create A Charge Separated State In De Novo Designed Proteins, Eskil Me Andersen

Dissertations, Theses, and Capstone Projects

To create an efficient de novo photosynthetic protein it is important to create long lived charge separated states. Achieving stable charge separation leads to an increase in the efficiency of the photosynthetic reaction which in turn leads to higher yields of end products, such as biofuels, electrical charge, or synthetic chemicals. In an attempt to create charge separated states in de novo proteins we hypothesized that we could engineer the free energy gaps in the proteins from excited primary donor (PD) to acceptor (A), and A back to ground state PD such that the forward electron transfer (ET) would be …

A New Mathematical Theory For The Dynamics Of Large Tumor Populations, A Potential Mechanism For Cancer Dormancy & Recurrence And Experimental Observation Of Melanoma Progression In Zebrafish, Adeyinka A. Lesi

Dissertations and Theses

Cancer, a family of over a hundred disease varieties, results in 600,000 deaths in the U.S. alone. Yet, improvements in imaging technology to detect disease earlier, pharmaceutical developments to shrink or eliminate tumors, and modeling of biological interactions to guide treatment have prevented millions of deaths. Cancer patients with initially similar disease can experience vastly different outcomes, including sustained recovery, refractory disease or, remarkably, recurrence years after apparently successful treatment. The current understanding of such recurrences is that they depend on the random occurrence of critical mutations. Clearly, these biological changes appear to be sufficient for recurrence, but are they …

Long Term Nutrient And Chlorophyll A Dynamics Across Long Island Sound And Impacts On Dissolved Oxygen Conditions Within The Western Sound (1991-2019), Sherry Perreira

Dissertations and Theses

Nitrogen overload, eutrophication, and hypoxia have been challenging and persistent water quality problems in Long Island Sound (LIS) over the past decades with major impacts on commercial industries, ecology, and recreational activities in the region. Recognizing these problems, the EPA enforced three phases of the Clean Water Act (CWA) to reduce nitrogen loads in an effort to improve this important estuary. This study examines how nitrogen (NH₃, NO_x & TDN), chlorophyll a (CHLA), and dissolved oxygen (DO) concentrations changed in LIS over the past 30 years, in response to water quality regulations as well as changes in …