Analysis and Development of Database Resources for the Integration of Transporter Protein Research Across Biological Disciplines with an Emphasis on Vacuolar Transporters in Plants
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Analysis and Development of Database Resources for the Integration of Transporter Protein Research Across Biological Disciplines with an Emphasis on Vacuolar Transporters in Plants

Abstract

Transmembrane transporter proteins facilitate an essential biological role in all living organisms by regulating the movement of substances across lipid membranes. The ABC (ATPase-binding cassette) and SLC (solute carrier) transporter superfamilies are a large, ubiquitous, and highly conserved subset of active transporters across all domains of life. These superfamilies are known to play a key role in xenobiotic defense mechanisms protecting cells from potentially harmful chemicals, known as multixenobiotic resistance (MXR), multidrug resistance (MDR) in cancer cells, and the transport of numerous endogenous substances.Due to their key influence on the absorption and distribution of chemicals, ABC and SLC transporters are of critical interest in pharmacology, with many resources devoted to characterizing drug-transporter interactions including databases like UCSF-FDA TransPortal. However, they are also of critical importance in other fields including aquatic toxicology, plant biology, nutrition, and microbiology. Information on transporter-chemical interactions from across such disciplines is currently disorganized and not contained in any publicly accessible database. Consequently, transporters are studied as a niche subtopic within other fields of study instead of as a self-sufficient discipline with relevance to many others. This thesis aims to alter that dynamic. First in this work, an analysis of the newly updated UCSF-FDA TransPortal + UCSD/UCD-NIEHS TICBase is given, elucidating trends in drug transporter research and making recommendations for the field. Second, we present a new database, UC Transportal, an expansive data resource meant to integrate transporter research from across biological disciplines and become a central repository for all ABC and SLC transporter interaction data. Third, a method development project to isolate intact vacuoles from Arabidopsis thaliana leaves is described to support plant vacuolar transport studies, with glycosylated monolignol transport as a topic of primary interest.

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