Date of Degree

6-2017

Document Type

Dissertation

Degree Name

Ph.D.

Program

Chemistry

Advisor(s)

George John

Committee Members

Shubha Govind

Ruth E. Stark

Diana Bratu

Thomas Neubert

Subject Categories

Ecology and Evolutionary Biology | Genetics | Lipids | Materials Chemistry

Keywords

Aspirin, JAK-STAT, Molecular rotor, Molecular gel, Butterfly pigments, Batesian mimicry

Abstract

The first chapter will introduce the work carried out in collaboration with the Govind laboratory at CCNY. Our quest was set forth to investigate the intimate relationship lying between chronic inflammation and tumor development. For at least the last fifteen years much research has been conducted on this topic; yet, the level of complexity arising from exceedingly interwoven biochemical pathways in mammals has resulted in slow advancements in this field. This is why we resorted to a simple yet powerful immunogenetic model organism, the fruit fly Drosophila melanogaster, in combination with the administration of the most common anti-inflammatory drug, that is aspirin, that in recent years has shown remarkable anti-cancer properties. We induced chronic inflammation and tumor development through the constitutive expression of pro-inflammatory signaling pathways in genetically-tractable Drosophila models. Upon aspirin treatment we discovered aspirin-triggered fatty acid derivatives with known potent anti-inflammatory properties in humans. Aspirin administration concurrently restored immune and lipid homeostasis, rescued microtumor-inflammation and improved viability. Aspirin’s coordinated effects on immune signaling and bioactive lipid circuitry suggest novel but conserved chemoprotective mechanisms for therapeutic intervention at the earliest stages of tumor development.

The second chapter will present an original approach for the development and study of small fluorescent compounds that are able to respond to changes in local viscosity for in vitro applications. Even though these molecules were originally designed to be tested directly in live cells and image compartments with different fluidity (cell membrane, cytoplasm, etc.), we decided to take a step back in order to first have a clear idea on how these novel viscosity probes behave in highly heterogeneous environments, such as the inside of a cell, and render this question easier to address. In order to develop a robust model, we took advantage of the John lab’s expertise and employed molecular gels that in spite of their solid-like nature mostly consist of liquid-like regions in which is present a physically distinct network of orderly arranged gelator molecules. This approach allowed us to make outstanding discoveries regarding the nanoscopic architecture of the gel under study as well as the photophysics underlying the behavior of these probes. I acknowledge that some material in Chapter 2 (paragraphs 1.1 - 1.4, 3.1 and 3.2) was previously published in my Master’s Thesis with the title “Synthesis and characterization of viscosity-dependent fluorophores for bioanalytical use”.

The final chapter will show how a chemical approach can be interestingly adopted even in the case of research in evolutionary biology. This collaborative project with Dr. Lohman at CCNY had the ambitious goal to prove that two butterfly sub-populations belonging to the same species (Elymnias hypermnestra) develop chemically different sets of wing pigments as a result of residing in geographically distinct regions (Thailand and Indonesia). So far the evolutionary biology community has mainly been interested in a genetic approach aimed at identifying subtle changes in the organism’s DNA sequence due to adaptation to a certain environment, predator, diet, etc. The present study tries for the first time to expand the tools available to biologists studying the evolution of butterfly as well as other organisms by looking at “chemical phenotypes”, namely variations in the chemical composition of wing pigments. Among specific aspects that will be thoroughly discussed later, this project also resulted in the remarkable discovery of previously unknown pigments that broaden our knowledge in naturally-occurring compounds.

This work is embargoed and will be available for download on Saturday, February 23, 2019

Graduate Center users:
To read this work, log in to your GC ILL account and place a thesis request.

Non-GC Users:
See the GC’s lending policies to learn more.

Share

COinS