Research Projects

Glycopolymer Synthesis

In collaboration with Prof. Shishir Chundawat’s group in Chemical and Biochemical Engineering, the Gormley lab is using it’s automated, high-throughput polymer synthesis platform to create libraries of synthetic glycopolymers for use in a variety of applications, including creating high-affinity ligands for lectin purification and the creation of biomedically-relevant synthetic glycoproteins, such as mucin.

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Stabilization of Chondroitinase ABC using heteropolymers for SCI injury repair

Single enzyme nanoparticles (SENs) are used for stabilization of Chondroitinase ABC (chABC), an enzyme that is used for treating spinal cord injuries but suffers from instability under physiological conditions. The Gormley lab uses an automated liquid handling robot (PolyTron) for high through synthesis of polymer candidates that are quickly evaluated for their ability to stabilize chABC. Machine learning algorithms are used to analyze data and predict new polymers that have the ability to further improve the stability of chABC. Best polymer-enzyme constructs are characterized using dynamic light scattering (DLS) and circular dichroism (CD) and tested in vitro and in vivo for downstream applications.

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Automation of Controlled Living/Radical Polymerization

The last decade has seen a significant increase in the use of polymers for biological applications from drug delivery vehicles to materials for tissue engineering. While large combinatorial libraries of polymers have historically been difficult to develop due to the oxygen sensitivity of polymerization techniques, recent oxygen tolerant polymerization chemistries such as PET-RAFT are quite amendable to high-throughput techniques. This project focuses on adapting liquid handling robotic system that enable researchers to design and synthesize nanoscale polymers in an automated fashion. So far, the Gormley lab has shown the ability to synthesize polymers in both 96 and 384 well plates simultaneously. Additionally, this platform is capable of advanced synthetic procedures such as the synthesis of block copolymers and post-polymerization functionalization with strain promoted azide-alkyne cycloadditions (SPAAC) click chemistry. Going forward, the aim of this platform is for it to become a tool for high throughput synthesis of easily customizable polymers for various biological interfaces.

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Polymer Design and Biophysical Characterization

In 2019, the Gormley lab characterized a large combinatorial polymer library to quantify compactness and flexibility by dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS). Through this work, it was found that hydrophobicity of the polymer backbone impacts both the flexibility and compactness of the polymer (Upadhya et al., Macromolecules 2019). The lab has also characterized and validated gel filtration columns and 96-well plates that can be used to purify small molecule impurities associated with PET-RAFT polymerization and bioconjugation (Upadhya et al., Macromolecular Rapid Communications 2019).

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Multivalent polymer design, synthesis and characterization

Prior research has shown that multivalent nanoparticles have the ability to increase receptor-ligand binding affinity and specificity. This project is to take advantage of this idea to synthesize a multivalent BMP-2 nanoparticle to promote and accelerate osteogenesis. Utilizing the reagent handling machine available in lab as well as an oxygen tolerant polymerization method PET-RAFT, he will be able to automate the synthesis of a large library of potential multivalent polymer candidates. The candidates are screened for compactness and flexibility using dynamic light scattering (DLS) and binding affinity to the BMP receptor using surface plasmon resonance (SPR). The long-term goal is to create a library of optimized multivalent nanoparticles to be used in the building of a Quantitative Structure-Activity Relationship (QSAR) model for multivalency.

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Automated Gel Permeation Chromatography Data Analysis

Python scripts are being used to automate the analysis of GPC data. This provides an accurate and fast platform for high throughput polymer characterization, specifically polymer molecular weight data. (see right image)

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Lightbox for High Throughput Polymerization

A lightbox device is being developed to be used in conjunction with PET-RAFT that allows for polymerization control. This is being used with PolyCraft to aid in high throughput polymer testing and development.

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