CAREER: Machine-guided design of enzymatically-synthesized polymers optimized for digital information storage

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There is a growing need for new information storage methods that can bridge the ever-widening gap between data generation and our ability to store it. Molecular information storage is a promising solution to this problem because it has key advantages over traditional storage media (e.g., magnetic tape and disk). These advantages include extremely high density, long shelf-life, and low energy costs. However, to make molecular information storage practical, several barriers must be overcome. Namely, the relatively high costs associated with reading and writing data in molecular form. This research is focused on harnessing the advantages of two promising technological areas originally developed for the life sciences (enzymatic DNA synthesis and nanopore DNA sequencing) by developing a new information storage medium based on synthetic polymers that can be synthesized at large scale and low cost, and can be quickly decoded with inexpensive laptop-powered nanopore readers. Together, these features will lower the cost, complexity, and latency of this system compared to traditional DNA-based data storage. As part of this award, the investigators are also committed to training students and professionals to be well versed in the intersection of biology and computing, which is a very promising new area of scientific and economic development. These research directions will be integrated into a new special topics course in which computer science students will be exposed to the concepts of molecular computing and information storage, while also gaining hands-on experience in molecular biology and computer hardware.This award aims to achieve the following goals: (1) Machine-guided design and chemical synthesis of new dNTP analogs; (2) Concatenation of these analogs into homo- and heteropolymer copolymers using enzymatic synthesis; (3) Demonstration of encoding digital information into copolymer sequences; (4) Computational models for predicting nanopore ionic currents from new analog sequences and for decoding new analog kmer signals into representative bits. Ultimately, the investigators expect to be able to demonstrate in their results that synthesis of an expanded polymer alphabet is possible as is encoding digital information using it. The ability to read this information out using nanopore technology will be a key driver of the system's high-throughput and low latency thanks to the portability and cost compared to mass spectrometry, which is the traditional readout for non-natural polymers. In its sum, this work represents a significant step forward in the feasibility of practical, large-scale digital data encoding in molecular form.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.