RNAs play pivotal roles in the cell due to their structures. RNA disfunction is implicated in many diseases, including cancers and neurodegenerative disorders, making RNA a critical drug target. However, the flexibility of RNA, its anionic nature, limited chemical diversity, and nonfunctional sites pose significant challenges in drug design. Furthermore, the chemical space of known RNA-binders is limited to non-drug-like compounds. Recent studies have suggested that RNA is a viable drug target as pockets have been found that are comparable to those found in druggable proteins and various assays have found drug-like compounds that bind to RNAs. These recent findings suggest the existence of a chemical space of drug-like RNA-binders. To enable the development of RNA targeted therapeutics, this chemical space must be characterized. However, current methods to detect RNA-ligand interactions are either limited in their throughput or in the chemical scaffolds and targets that can be evaluated. This study aims to introduce the application of DMS-MaPseq as a high-throughput approach to evaluate a larger chemical space for RNA binding. This chemical probing technique modifies nucleotides based on their solvent accessibility, which is detected through reverse transcription and sequencing. The novelty in this approach is in utilizing multiplex sequencing which enables the evaluation of thousands of potential RNA-ligand interactions. To standardize this application of DMS-MaPseq, a set of known binding interactions will be evaluated to provide a standard set of data for binding. This will then provide a basis for high-throughput assays for the discovery of novel RNA-binding molecules.

There is a growing medical and scientific problem centered on the efficiency of antibiotics, which are used to stop the spread of bacteria-causing diseases. Antimicrobial resistance (AMR) is a growing concern as bacteria continue to develop antibiotic immunity. This research focuses on the design and preparation of antimicrobial polymers (AP) as an alternative strategy to combat AMR. Previous research has shown that AP's effectiveness against bacteria depends on amphiphilicity and cationic charge. This study aims to optimize the synthesis of various monomers using amino acid-based reagents, such as lysine, and to prepare these monomers as antimicrobial peptides (APs) for evaluation of their antimicrobial activity. The designed monomers were synthesized by reacting lysine reagents with aminoethyl methacrylamide (AEMA) using different coupling reagents, such as EDC and DIC, via nucleophilic acyl substitution reaction. Through this research, we can establish structure-activity relationships by evaluating a panel of lysine-derived cationic amphiphilic polymers and identify potential leads as APs.

New antibacterial drugs are urgently required to treat drug-resistant bacterial infections. The development of treatments for gram-negative bacteria is challenging due to the need to breach the impermeable outer membrane, which restricts the diffusion of most molecules larger than 600Da. To overcome this, antibiotics must be small enough to pass through membrane porins or sufficiently hydrophobic to penetrate the membrane directly. Class II microcins are an underexplored class of bacteriocins which offer a promising avenue to address this problem. Microcins, which are small antibacterial proteins, are secreted by bacteria and bind to specific outer membrane receptors to reach their antibacterial targets. However, our understanding of microcin biology has been hindered by challenges in their identification and limited characterization due to few known examples. Our research group recently developed a bioinformatics and in vitro confirmation pipeline which uncovered numerous novel class II microcins across various bacterial families. This project focuses on EN112, a class II microcin that targets OmpF outer membrane receptors for uptake and is active against a diverse range of bacterial strains. Here, the uptake domain of EN112 will be identified. Then, key amino acids of the uptake domain and OmpF that interact to facilitate uptake will be identified. Successful uptake of modified uptake domains through OmpF and into the periplasm can be quantified using a split-luciferase assay. Through these investigations, we seek to learn how EN112 crosses the bacterial outer membrane so that this information can be used in the development of antibiotics targeting gram-negative bacteria.

Vanadium (IV) oxide (VO2) is a canonical semiconducting material that undergoes a metal-to-insulator transition (MIT). This property presents the unique opportunity for this structure to serve as the material for smart windows, sensors, and neuromorphic materials. For this, control over the temperature range and hysteresis width where the MIT occurs is of great interest due to its direct relationship to the application. Approaches that include substitutional doping with several transition-metals, stabilizing ultrasmall particles (1-2 nm of width), and morphology changes have demonstrated to serve as a synthetic knob to tailor the MIT. The De Jesús Báez lab has recently developed a synthetic route for non-conventional morphologies (clustered rods and nanostars) of VOOH, a protonated structure of VO2. In this work, we seek to elucidate the mechanism of transformation of VOOH to VO2 by reacting VOOH with a base. We hypothesize that by exposing VOOH to a base, we are able to retain the morphology from VOOH and effectively transform the material to VO2.