Publication Date

2016-11-11

Availability

Embargoed

Embargo Period

2018-11-11

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Biochemistry and Molecular Biology (Medicine)

Date of Defense

2016-11-01

First Committee Member

Sylvia Daunert

Second Committee Member

Sapna Deo

Third Committee Member

Joaquin J. Jimenez

Abstract

Advancements in diagnostics and therapeutics arise from acquiring new knowledge of biochemical and molecular processes. These breakthroughs can mean a quicker and more precise diagnosis, more efficient therapeutic treatments and a better quality of life for patients suffering from a disease. To better serve patients, scientists must find new and improved diagnostic tools and treatments. This starts by recognizing a shortcoming of the current methodologies or an unmet need in the medical field. The aim of the research of this thesis is to implement bionanotechnology strategies to generate new technologies to aid in the diagnosis and treatment of certain health conditions. The studies herein focus on binding of molecules to ligands, formulating delivery vehicles for drug transport, and targeting therapeutics to sites of injury. In the first part of the thesis, work toward developing new diagnostic/sensing systems for bacterial-related diseases was performed. In that regard, we focused on understanding ligand binding to further unravel the mechanism of bacterial communication by using Pseudomonas aeruginosa as the model system. Specifically, the work centered on developing a strategy for the preparation of the quorum sensing protein LasR, the sensing protein that we planned to use in our studies for the development of biosensors as diagnostics tools for bacterial disease or diseases with a heavy bacterial component. Protocols were optimized to obtain the soluble LasR ligand-binding domain (LBD) in the unbound state, which is essential for performing binding studies of the protein with the quorum sensing molecules of the bacterial communication system of Pseudomonas aeruginosa. Next, the focus centered on the development of drug delivery technologies for small drugs and for stem cells. The first project aimed at designing a drug delivery system for transdermal administration of a small well-known drug. Specifically, the need to administer the erectile dysfunction drug sildenafil citrate locally resulted in the formulation of a liposomal delivery platform that shows promising characteristics. In a separate project, we addressed the current need for improved inflammatory bowel disease treatments by developing a nanocarrier platform for the targeted delivery of stem cells to the gut. The developed approach has shown in mice models of inflammatory bowel disease its ability to selectively home stem cells to the site of injury and inflammation in the intestine of the mice.

Keywords

diagnostics; therapeutics; protein expression; biosensor; transdermal delivery; nanocarrier

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Available for download on Sunday, November 11, 2018

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