Headshot portrait of Isaac Applebaum - Bio-X Undergraduate Fellow
2021 & 2022 Undergraduate Summer Research Program Participant

Home Department: Biology

2021 Research Project: “Designing Improved Polymers for Application-Specific Gene Delivery with Graph Neural Networks and Non-Convex Optimization Algorithms”

2021 Mentors: Robert M. Waymouth (Chemistry) and Grant Rotskoff (Chemistry)

The Waymouth lab has created polymers called Charge-Altering Releasable Transporters (CARTs) that carry genetic material, such as RNA or DNA, into cells. CARTs have been used to develop successful cancer immunotherapies and mRNA vaccines for COVID-19 in mice, applications that each require gene delivery to specific cell types and organs. Varying the chemical structure of CART polymers leads to remarkable variation in the cell types and organs that genetic material is delivered to, but these relationships between chemical structure and biological function are poorly understood. Working in the Waymouth and Rotskoff labs, Isaac will use cutting-edge machine learning techniques to elucidate these connections and design improved CART polymers that can meet the unique needs of cancer therapies, vaccines, and treatments for genetic disease.

2022 Research Project: “Designing Improved Polymers for Cell-Type Selective Gene Delivery using Novel Neural Network Architectures and Non-Convex Optimization Algorithms”

2022 Mentors: Robert M. Waymouth (Chemistry), Grant Rotskoff (Chemistry), and Ronald Levy (Medicine - Oncology)

With his mentors, Isaac will use flow cytometry of primary immune cells to measure selective mRNA transfection of targeted immune cell types by gene-delivering Charge-Altering Releaseable Transporter (CART) polymers, designed by their novel machine-learning algorithms for maximum selectivity. These experiments will complete a paper they aim to publish by the end of the summer on their work using neural networks, non-convex optimization algorithms, and high-throughput data collection to design optimal polymers for various gene-delivery applications. Isaac will run flow cytometry experiments, synthesize polymers, improve their machine learning and optimization algorithms, and help write their manuscript. Their work developing a novel gene delivery method that selectively targets cells could improve the manufacturing of FDA-approved cell-based therapies.