Current Students

Bradley Biggs

Bradley Biggs
2012 B.S. Chemical Engineering, University of Southern California
Ph.D. Advisor: Keith Tyo

Doctoral Research Project:
I work in the laboratory of Prof. Keith Tyo in Chemical and Biological Engineering. My research focuses on protein engineering within the context of whole cells. This comes predominantly in the form of the introduction of new chemical functionality by way of novel ligand binding domains or protein-protein interactions for the output of either chemical signal transduction or chemical synthesis. To accomplish these output goals, I care about the free energy of each protein fold, using computational approaches to evaluate this parameter, and appreciate both promiscuous enzyme functionality and specific cell contexts (E. coli, S. cerevisiae, etc.).

Evan Buechel

Evan Buechel
2015 B.S. Biochemistry, University of Wisconsin - Madison
Ph.D. Advisor: Heather Pinkett

Doctoral Research Project:
The multiple drug resistance phenomenon that occurs in bacterial and fungal infections, as well as human cancer, is primarily the result of the upregulation of a set of ABC transporters that are capable of exporting a wide range of xenobiotics. In S. cerevisiae, the master regulator of this set of ABC transporters is the transcription factor Pdr1p, which has homologs in humans and in bacteria. Currently, it is known that Pdr1p is capable of binding xenobiotics, and what DNA sequences it binds to. Through structural and biochemical studies, I will answer how Pdr1p binds xenobiotics and identify what conformational changes it undergoes to upregulate transcription.

alec castinado

Alec Castinado

Ph.D. Advisor: Keith Tyo

Doctoral Research Project:
As interest and research surrounding the unprecedented data-storage potential of DNA continue, engineered DNA polymerases are poised to be a natural companion technology. I am working toward the realization of polymerase-based tools capable of encoding a record of changing intracellular conditions over time in a DNA template, allowing complex biological systems to collect data on themselves without excessive interference from external influences. Specifically, these tools are being developed with the goal of recording functional connectivity in the mammalian brain at single-cell resolution. By developing novel assays for polymerase function, I am expanding the accessibility of DNA polymerases to high-throughput protein engineering techniques with the expectation that these techniques, in concert with computational protein design tools, will produce novel polymerase functionalities that facilitate the real-time encoding of information in DNA.
Janel Davis

Janel Davis
2014 B.S. Biomedical Engineering, University of Texas at Austin
Ph.D. Advisor: Hao F. Zhang

Doctoral Research Project:
Recent advances in super resolution imaging techniques have presented the opportunity to investigate new detection and diagnosis methods. Working with collaborators, the Zhang lab has developed a spectroscopic photon localization microscopy (SPLM) platform. SPLM utilizes extrinsic emission to locate and detect spectral signatures with high spatial and spectral resolution. My research will use bacterial drug resistance as a model to demonstrate how this nanoscopic imaging platform can be used to detect and study nucleic acids. This technology has the potential to have many applications in the discovery, detection and characterization of numerous diseases. Additionally, the improved resolution is ideal for studying the process of gene expression which will allow us to better understand how pathogens become drug resistant and virulent.

nolan kennedy

Nolan Kennedy

Ph.D. Advisor: Danielle Tullman-Ercek

Doctoral Research Project:
Bacterial microcompartments are proteinaceous subcellular organelles that are utilized by numerous prokaryotes as a means of either increasing enzymatic efficiency or sequestering harmful intermediates in specialized metabolic pathways. These compartments are composed of thousands of small self-assembling protein subunits of multiple types. Specifically, my work focuses on the 1,2-propanediol utilization microcompartment found in Salmonella typhimurium. My work will look at how the proteins forming these unique organelles assemble into larger structures, such as rods, sheets, or complete compartments. Once the rules governing the assembly of these structures are elucidated, we hope to utilize them to create designer protein structures for scaffolding or drug delivery.

sara rigney

Sara Rigney

Ph.D. Advisor: Carole LaBonne

Doctoral Research Project:
Vertebrate development is a progressively restrictive process in which initially pluripotent cells capable of giving rise to all cell types become lineage restricted to specific fates.  While pluripotency in most embryonic cells is transient, an exception lies in the neural crest cells, which maintain their differential potential late into development.  Neural crest cells give rise to a diverse population of cells that contribute to the vertebrate body plan, and their defects are linked to many forms birth defects and cancer. In the LaBonne lab we utilize neural crest cells as a model to study the mechanistic controls of signaling pathways, transcription factors and epigenetic modifiers on pluripotency and lineage restriction.  My project is currently focused on developing powerful fluorescent imaging assays in both live and fixed Xenopus laevis embryos that will allow us to visualize and quantify the changes in gene activity at a single-cell resolution throughout embryogenesis, in order to understand how seemingly random cell to cell differences drive the restrictive developmental decision making of the embryo.

matthew robey

Matthew Robey
2013 B.S. Biochemistry and Molecular Biology
Ph.D. Advisor: Neil Kelleher

Doctoral Research Project:
Modern medicine relies heavily on microbial natural products with diverse structures and a wide range of pharmacological activities. With the advent of affordable and accessible genome sequencing, it has become apparent that an extraordinary wealth of bioactive natural products awaits discovery. The main goal of my research is to establish a cell-free protein synthesis-based system for reconstitution of natural product biosynthetic pathways, a system greatly enabled by high resolution LC-MS proteomics and metabolomics detection. This platform will allow for natural product discovery, pathway prototyping, and mechanistic studies of biosynthetic enzymes.

silverman

Adam Silverman
2016 B.S. Chemical and Biomolecular Engineering (Biotechnology Concentration), Georgia Institute of Technology
Ph.D. Advisors: Julius Lucks and Michael Jewett

Doctoral Research Project:
In the Lucks and Jewett labs, I am working on a project to engineer riboswitches, RNA-based biosensors, for the detection of both cellular and xenobiotic ligands in cell-free environments. Compared to traditional chemical sensors or cellular biosensors, cell-free biosensors are easier to test, respond more quickly, and can sense a wider array of compounds that may be toxic or impermeable to cells. By using RNA to detect target ligands, we can leverage structure-guided approaches that map transcript folding pathways towards the rational design of new riboswitch variants. I am also working on developing a cell-free protein synthesis platform optimized for rapid ligand detection which would be thermostable and field-deployable.

jonathan strutz

Jonathan Strutz
2015 B.S. Chemical and Biomolecular Engineering, Ohio State University
Ph.D. Advisors: Linda Broadbelt & Keith Tyo

Doctoral Research Project:
Lignin, a plant-based polymer, is currently a waste product, but it shows promise as a feedstock for pharmaceutical production. However, because of the diversity of chemical linkages within lignin, its depolymerization results in a diverse soup of aromatic monomers and oligomers, requiring costly separation methods to purify valuable components. To overcome this limitation, my research focuses on funneling this diverse mixture of aromatics into the metabolism of an aromatic-degrading organism, Acinetobacter baylyi ADP1. However, ADP1 comes with its own engineering challenges, including complex regulatory effects. To overcome these challenges, I am developing a kinetic model of ADP1 metabolism. The model will be used to infer unknown regulatory effects, identify metabolic bottlenecks and strategies for overcoming complex regulation, and simulate production of target molecules. Hopefully, this will allow us to intelligently engineer a strain that can utilize lignin in the production of life-saving small-molecule drugs.