BIOTECHNOLOGY TRAINING PROGRAM

Doctoral Research Project:  Virus-like-particles (VLPs) are nanomolecules composed of many replicate subunit proteins, have the ability to self-assemble, and can act as therapeutic cargo carriers. However, VLPs still lack certain characteristics needed for cargo delivery, such as environmental stability or a cargo release mechanism. Using male-specific bacteriophage 2 (MS2) as a model for VLP assembly, the Tullman-Ercek group has discovered key biophysical properties that govern VLP self-assembly. To further learn more about VLP self-assembly, I will create an epistatic double mutant library of MS2 variants. Then, MS2 variants will be screened and I will characterize their physical properties, such as pH sensitivity, thermo stability, and capsid assembly.

Doctoral Research Project:  Food insecurity is an ongoing crisis currently affecting over a quarter of the global population. A major contributor to this public health concern is the reduction of agricultural productivity due to infection of staple crops by viral pathogens, resulting in losses amounting to approximately $30 billion every year. A pivotal step in plant viral pathogen management is the development of highly sensitive, specific and user-friendly diagnostic methods. Isothermal viral target amplification strategies can be paired with CRISPR-Cas systems to meet these specifications and enable rapid and accurate point-of-use detection. My current work involves combining the unique advantages offered by one such amplification strategy – NASBA – with that of CRISPR-Cas13a cleavage activity to develop a broad-range plant virus detection platform for field applications. To enable automated design of key NASBA-Cas13a assay components to detect emerging plant pathogens, I will develop an algorithm that utilizes machine learning strategies as well as viral sequence and structural properties to predict optimized gRNA and primer pairs. This computation-driven diagnostic platform will help meet the growing need for reliable, field-deployable assays for plant disease surveillance.

Doctoral Research Project:  GBM is an extraordinarily aggressive and most common primary brain
cancer in adults. Despite the standard of care treatment consisting of surgery, radiation, and chemotherapy, the median survival rate remains below 15 months. One of the hallmarks of GBM is the vast intra-tumoral heterogeneity. Gliomas display expansive differential expression of tumor antigen receptors, such as epidermal growth factor variant III (EGFRVIII) and interleukin 13 receptor α2 (IL-13Rα2). Chimeric antigen receptor (CAR)-T cells cell therapy has demonstrated efficacy against certain cancers. However, the effectiveness of single-targeted immunotherapies is severely limited in GBM. My project aims to address the problem of antigen escape by developing novel versatile multispecific CAR-T cells directed to glioma cells expressing distinct antigens, aiming to provide better tumor coverage. This therapy will employ single-domain antibodies, known as nanobodies (Nbs). Nbs have distinct advantages over traditional monoclonal antibodies, 1) they are smaller than single-chain variable fragment (scFv), and 2) highly stable. I will engineer a library of Nbs specific for the common GBM antigens. This system enables T cells to recognize GBM cells regardless of their antigen expression profile, mitigating the risk of antigen escape.

Doctoral Research Project:  My PhD research centers on discovering mechanisms by which organisms control mineral deposition with the end goal of exploiting these techniques to improve
synthetic materials processing. My work will focus on the sea urchin, a model organism for embryonic spiculogenesis. The sea urchin endoskeleton is formed from spicules of single crystal
calcite that demonstrate both triradiate and linear growth as they develop. This degree of control
over the shape and direction of the calcite mineral growth is unparalleled in current single crystal
synthesis techniques. Primary mesenchyme cells (PMCs) are the mineralizing operatives of the sea
urchin embryo and incubating them in different concentrations of vascular endothelial growth factor (VEGF) dictates the crystallographic axis direction and shape of the growing spicule. The goal of my current project is to clarify the relationship between PMC ultrastructure and VEGF signaling in the spicule growth process.

Doctoral Research Project: I investigate microbial metabolism and its ability to adapt on an hours-long timescale (regulation of enzyme-expressing genes) and on a generations-long timescale (evolvability). I hope gaining a better understanding of these forms of adaptation will improve our ability to design sustainable bioprocesses that meet the material and energetic demands of society.