Join us for a chat with Sam Schaffter, a postdoc at NIST working on realizing complex transcription-based strand displacement in living systems. We start the conversation with the story of how he made the transition from the molecular biology of food to molecular programming. We then move on to the details of his research on transcriptional circuits including where the idea came from and the trials of taking molecular computing from the test tube to cell systems. He tells us about the differences and similarities between academic and government research and how everything is a “measurement” when you work for NIST. We round out the conversation with Sam’s dreams of the future of nucleic acid-based sensors for diagnostic and control purposes and the research he would like to see in the next 5, 10, 25 and 50 years to advance the field toward application.

Sam conducted his PhD research in the field of DNA nanotechnology and DNA computing, working in Rebecca Schulman’s group at Johns Hopkins. He developed synthetic transcription-based networks with dynamics programmed via Franklin-Watson-Crick base pairing rules. These in vitro networks emulated key functionalities of cellular genetic regulatory networks and thus could serve as a programmable “synthetic genome” for controlling nucleic acid materials and devices, such as DNA nanostructures and DNA-responsive hydrogels. The goal of his research was to engineer synthetic materials capable of sophisticated behaviors seen in biology including hierarchical differentiation or self-healing. For this work, he won the 2021 Robert Dirks prize for molecular programming

As a National Research Council (NRC) postdoctoral fellow at NIST, Sam is interested in moving DNA computing circuits from the test tube to living cells. Current DNA-based circuits are only single use and suffer from degradation in vivo, limiting their practical applications. To overcome these limitations, Sam’s current research focuses on transcriptionally encoding RNA-based circuits, equivalent to those developed in DNA computing, that can operate continuously inside living cells. These circuits could be programmed to recognize complex differential gene expression patterns in real-time in vivo, potentially enabling a new class of living measurement systems.

Sam’s project at NIST: https://www.nist.gov/programs-projects/cellular-measurement-and-computation-rna-circuits
Co-transcriptional RNA strand displacement circuits: https://www.biorxiv.org/content/10.1101/2021.07.20.450530v1
Call for applications to the NIST Cellular Engineering Group: https://molpi.gs/files/220114-nist-call.pdf

For non-US citizens, the process for applying is essentially to contact someone at NIST you want to work with and to discuss potential projects. If NIST has available funding to hire students for a specific project, then the student can be hired through an external university. This process is actually done for both US an non-US citizens depending on need / the situation. There isn’t a funding mechanism like the NRC fellowship for non-US citizens so it depends more heavily on existing funding. But nonetheless, any interested international students are encouraged to reach out about available opportunities.

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Find more information at the episode page here:
https://podcast.molpi.gs/media/schaffter-s-1c8799780ad4af6f/