My Research Projects
Deuterium Adduct Bioactivity Screening
Background
Natural product discovery pipelines suffer from a number of issues that has led to recent struggles in the identification of new molecules with potent or relevant bioactivities (ex. antibiotics, anticancer drugs). One concept proposed by this project was the desire to detect molecules that may at native titers be too low to detect an obvious bioactivity, but may in fact be able to perform as drug candidates.
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Project
This projects goal was to develop a novel screening platform utilizing tags that swapped out hydrogen with deuterium as a means of non-invasively labeling small molecules. These tagged compounds are then bound to human cancer cell lines as a means of detecting intrinsic bioactivity of these molecules.
Skill Sets Developed
Coding and Data Processing: I designed multiple programs in Matlab and Python to help allow for ready detection of these molecules. Using a combination of data importation, queried searching, and library mining to allow for predictive isotope abundances, I was able to develop a program with a <1% false negative likelyhood for detection of these molecule. This feat is by far my favorite accomplishment in grad school.
Mass Spectrometry: Furthering complex data processing, I developed skills in the usage and design of experiments around liquid chromatography mass spectrometry. I've gained expertise and am now the mass spec technical expert of my lab. This has lead to a number of collaborations with both my lab mates and even exteral labs on campus (publication to come).
Microbial and Mamallian Cell Culturing: Outside of my data handling, I've developed a versatile skills set in culturing that spans the phylogenetic tree of life.
Oral Microbiome
Background
The human mouth has a fascinating microbiome. Some of these bacteria can assist preventing tooth decay; others have developed specialized weapons that cause it. My work on this project focused on an array of genes that are expected to endow Streptococcus mutans, a bacterial family that causes dental plaques, with extrodinary prowess in the microbiome. These genes make molecules that can play a wide role in a number of activities including roles as antibiotics, biofilm formation, quorum sensing, metal binding, and cell surface hydrophobicity adjustments. These molecules give the bacteria some powerful abilities that we want to better understand, and potentially use to aid in human health.
Project (some vagueness required due to prepublication status)
Our project has narrowed in one of these gene clusters and the discovery of the molecule that it generates. We have both identified the molecule, purified and discovered its structure, and discovered a powerful bioactivity that it endows into its microbe.
Skill Sets Developed
Comparative Metabolomics and -omics work: This project required the usage of comparitive mass spectrometry, RNA-omics and Prote-omics experiments. All of these data contributed to produce a vivid image of the molecules role in these dangerous strains.
Small molecule and protein purification: Extensive experience in many types of chromatography allowed for the purification of the target metabolite from thousands of other molecules. A particular point of pride was my ability to purify enough of this molecule to perform structural NMR; the yield of this compound is <1 mg per 20Ls of bacteria. Purification of the domain proteins involved in the manufacturing of the molecule also allowed me to exercise my skills in protein purification.
Bioactivity Assay Screening: Identifying the bioactivity of this molecule required a complex array of experiments ranging from attempts to bind the molecule to transition metals, all the way to determining if it had anti-cancer activity. Beyond the actual tests themselves, this portion of the project exercised my abilty to rapidly assimilate new techniques and to efficiently gain proficiency.
