William Marsh Rice University

Efri Begin Oi: Engineered Bacterial Consortia for Parallel Biocomputing -this Award Will Support Research to Develop New Platforms for Biological-electronic Communication That Can Be Harnessed for Biological Computing, Based on Microbial Sensing and Communication. Microbes Both Sense and Respond to Their Environments. These Processes Can Be Complex, Even for a Single Microbe. Microbes Also Communicate With One Another, Often Through Chemical Signaling, But Sometimes Using a Form of Electrical Signaling. This Communication Can Result in a Collective Response. Viewing Each Individual Microbe as an Information Processor Offers the Possibility of Connecting the Microbes Together to Create a Complex Living Computer. This Project Seeks to Connect Microbes Through Electronic Networks, Organized to Perform Intelligent Behaviors, Such as Learning Complex Patterns. Such Microbe-based Networks Could Serve as the Basis for Smart Sensors, for Example, Harnessing Biological-electronic Communication for Biological Computing. Importantly, This Technology Must Be Developed Safely and in Alignment With Public Values. in Support of This Goal, the Ethical, Legal, and Social Implications (ELSI) of Novel Biological Computers Will Be Investigated. This Research Could Enable Development of Programmable Living Biocomputers That Could Have Applications in Medical Monitoring. Microorganisms Are Capable of Sensing, Responding and Adapting to Their Environments. Such Biological Sensing and Information Processing Tools Could Be Harnessed to Detect and Interpret Complex Chemical Signatures Such as Biomarkers in Patient Samples or Contaminants in Environmental Samples. to Unlock This Potential, a Biocomputing Platform for High-dimensional Chemical Pattern Recognition Called the Electrogenetically-networked Cyber-bacterial Organoid Will Be Developed. These Synthetic Microbial Consortia Will Be Capable of Integrating Chemical and Electronic Inputs Into Electronic Outputs, Which Are Then Relayed to a Network of Parallel Consortia. to Implement Chemical Pattern Recognition, a Theoretical Framework That Combines Principles of Distributed and Biological Computing Will Be Developed. Next, the Computational Capabilities of the Bio-processors Will Be Extended Through Implementation of Cellular Memory and Adaptive Learning. This Will Require Development of Continuous Culture Systems That Maintain Long-term Microbial Activity and Support Electronic Interfacing. These Will Allow Learning and Iterative Response Refinement Through Long-term Electrogenetic Interfacing and Transcriptional Feedback That Sensitizes Cells to Inputs. These Intelligent Behaviors Will Be Used to Classify Chemical Signatures and Adapt to Changing Environments. Given That Intelligent Biological Computing Systems Raise Novel Questions About Responsible Development and Use, This Project Will Explore the Ethical, Legal, and Social Implications (ELSI) of Biocomputing, Focusing on Regulatory Frameworks, Public Perception, and Responsible Development of Bacterial Organoid Systems. This Integrated Approach Should Advance Both the Technical Capabilities and the Societal Readiness of Programmable Living Biocomputers With Applications in Diagnostics, Sense-and-respond Therapeutics and Other Monitoring Applications 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.- Subawards Are Planned for This Award.