Dissertation Defense Schedule
Academic Excellence
Sharing original dissertation research is a principle to which the University of Delaware is deeply committed. It is the single most important assignment our graduate students undertake and upon completion is met with great pride.
We invite you to celebrate this milestone by attending their dissertation defense. Please review the upcoming dissertation defense schedule below and join us!
PROGRAM | Bioinformatics & Computational Biology
From Single Amino Acid to Environmental Ecology and Back: The Saga of DNA Polymerase I
By: Rachel Keown Chair: Shawn Polson
ABSTRACT
Viruses, comprising a vast array of genetic diversity, are pivotal components of Earth’s ecosystems. Bacteriophages (phages), or viruses infecting bacteria, outnumber host populations by a factor of ten in marine environments and therefore have outsized impacts on microbially-mediated ecosystem dynamics. Metagenomic sequencing of viral communities (viromes) offers insights into this diversity and unveils the biochemical repertoire of novel viral enzymes. This dissertation investigates the biochemical characteristics of DNA polymerase I (PolA) enzymes encoded by environmental phages. PolA is encoded by an estimated 25% of dsDNA phages and is solely responsible for the faithful replication of the phage genome. Historical biochemical analyses and metagenome mining have shown that three variants of amino acid residues at a critical position responsible for nucleotide incorporation (762 in E. coli and 526 in Coliphage T7), result in distinct enzyme characteristics. Tyrosine at this position leads to very fast replication with a moderate mutation rate and is believed to be a marker of lytic phages. Phenylalanine slows DNA replication by 10-fold compared to tyrosine and is found in many bacteria and a wide range of viruses. Leucine, prevalent in many lysogenic phages and abundantly found in metagenome sequences, has been shown to slow replication by 1000-fold and decrease mutation rates. This study employs a multidisciplinary approach, utilizing biochemical assays on single-point mutant proteins and environmental proteins, genetic engineering of bacteriophage T7, and computational analysis to elucidate the functional roles of these residues, confirming their impact on enzyme activity and phage replication dynamics. Additionally, metagenomic data were used to classify viral populations across a depth gradient in the pelagic ocean, revealing novel 762 position identities such as histidine and glutamine, with currently unknown biochemical functions. The insights gained in this study have significant implications for both fundamental virology research and practical applications in biotechnology and environmental science.
The Process
Step-by-Step
Visit our “Step-by-Step Graduation Guide” to take you through the graduation process.From formatting your Dissertation to Doctoral Hooding procedures.
Dissertation Manual
Wondering how to set up the format for your paper. Refer to the “UD Thesis/Dissertation Manual” for formatting requirements and more.
Defense Submission Form
This form must be completed two weeks in advance of a dissertation defense to meet the University of Delaware Graduate and Professional Education’s requirements.
