Methylation of histone 3 lysine 4 (H3K4) catalyzed by the COMPASS family of lysine methyltransferases is universally associated with eukaryotic transcription. However, despite thousands of published studies examining the deposition, dynamics, and genomic positions of this chromatin modification, there is no clear consensus as to the molecular function or biological...
This work combines the use of high-throughput mass spectrometry with peptide arrays for to monitor reactions on peptides. The Mrksich lab introduced a high-throughput, label-free, biochemical assay that relies on self-assembled monolayers on gold and matrix-assisted laser desorption/ionization mass spectrometry, termed SAMDI-MS. This dissertation introduces new applications of SAMDI-MS and...
The work in this thesis focuses on computational methods for the identification of novel enzymatic pathways. In particular this work focuses on the utilization of the Biological Network Integrated Computational Explorer (BNICE) software suite to predict de novo enzymatic pathways for the production of commercially relevant compounds and on improvements...
SAMDI-MS (Self-Assembled Monolayers for MALDI-TOF Mass Spectrometry) couples the use of chemically-defined self-assembled monolayers of alkane thiolates on gold surfaces with MALDI-TOF mass spectrometry for rapid characterization of the surfaces. Reactions performed on the surfaces can be quantified directly by detection of the reaction substrates and products. This rapid detection...
Epigenetics is the study of chromatin-based events that regulate gene expression without the change of DNA sequence, including DNA methylation, histone modification and chromatin remodeling. Epigenetic regulators are encoded to modify chromatin in a highly regulated and dynamic manner. A growing number of studies have suggested the dysregulation of epigenetic...
More than half of proteins in humans are modified with carbohydrates in a process called glycosylation, yet this process remains poorly understood even though approximately 1% of the expressed human genome encodes biosynthetic machinery for glycosylation. Unlike genomics and proteomics where high throughput tools are now routinely used to generate...
The literature has established glucokinase (GCK) to be the principal hexokinase (HK) in the liver, operating as a glucose sensor to regulate glucose metabolism and lipid homeostasis. We have recently proposed Hexokinase Domain Containing-1 (HKDC1) to be a novel 5th HK with expression in the liver. Here, we reveal HKDC1...
One of the grand challenges in science is development of soft materials that mimic living organisms to optimize the way we use energy, translate or morph reversibly or sense their envi- ronment and respond in a useful fashion. Using the insights from studying biological structures, we hope to design soft...
Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated Cas proteins provide an immune-like response in many prokaryotes against extraneous nucleic acids. CRISPR-Cas systems are classified into different classes and types that vary widely in composition, target recognition, and overall mechanism. The main division of CRISPR-Cas systems occurs between...
Harnessing the metabolic potential of methanotrophic bacteria is a compelling strategy for the bioremediation of environmentally harmful methane gas. Methanotrophs can activate a 105 kcal/mol C-H bond in methane at ambient conditions using metalloenzymes called methane monooxygenases (MMOs). Particulate methane monooxygenase (pMMO) is a copper-dependent, membrane-bound enzyme that is the...