SemiSynBio-III: Towards Understanding and Controlling Redox for Microbial Memory and INteractions - TURIN

Modern electronics transformed our lives by allowing information to be communicated through electromagnetic radiation and processed through integrated circuits. Such electronic devices can transmit, receive and process digital information rapidly, cheaply and without error. Biology is also expert at information processing, typically communicating through various modalities (e.g., electrical, mechanical and molecular), and processing through cell-based “micro-processors” that are often embedded within multicellular systems (i.e., tissue or consortia).

Such biological systems can process noisy information to learn, adapt and store information for use by future generations. The long-term vision of this research is the fusion of orthogonal information processing capabilities in electronics and biology. This is denoted “bioelectronic communication” and the team is developing a new way of facilitating this transformative capability.

Their approach exploits electron flow and it bridges the gap that exists at the bio-device interface - electrons flow freely in microelectronics but are transferred in networked oxidation and reduction (i.e., redox) reactions in biology. By developing redox-linked synthetic biology that enables electron transfer to and from “smart” materials that, in turn, are electroactive components microelectronic devices, the team has already built the basis for opening new lines of bioelectronic communication.

A unique feature of their work will be the use of electronics to stimulate gene expression as well as to “write” retrievable “coded” information onto the genome of microbes. There are many opportunities envisioned for these capabilities. For example, with “biohybrid” devices built to enable these capabilities, one may be able to eavesdrop on and control our immune systems as they combat infections and guide wound healing.

These processes rely on redox communication. One may be able to explore the molecular communication in the GI tract or in the rhizosphere, where redox based signaling is also prevalent. Unraveling the complexities of these systems will help address the challenges of human health, environmental security, as well as food production and crop protection.

The TURIN multidisciplinary team is well-poised to not only develop the fundamental basis for bioelectronic communication, but to catalyze its transformation into practice through an extensive network of collaborations with industry and governmental agencies (i.e., NIST, FDA). Importantly, efforts will include the training of undergraduate and graduate students at the intersection of engineering, computer science and biology, and the development of a new summer school on redox-based bioelectronics.

The projects’s long-term vision is the fusion of orthogonal information processing capabilities of electronics and biology for the development of an emerging field of redox-based bioelectronics. The overarching hypothesis of this research is that the redox modality provides an unprecedented ability to interface biology and electronics because: (i) electrochemistry provides electronic access to this modality (i.e., redox signals can be readily generated and detected at an electrode); and (ii) redox is a native biological modality by which cells exchange information with their environment.

The project offers several important intellectual contributions across four Technological Focus (TF) areas. The first TF will fabricate biocompatible materials (i.e., thin hydrogel films) as an electronic layer that interconverts redox and electrical signals. These will transduce electrode-imposed inputs into biologically-recognized redox signals (e.g., H2O2, phenazines).

The second TF will create communicating cells capable of interconverting signals from the redox modality and a native biological signaling modality (quorum sensing autoinducers) to enable communication to a broader microbial population. The third TF will create decision-making cells that can be instructed by electric inputs to observe their context and perform context-dependent Boolean logic operations: either to write to their genome (permanent memory) or to adjust consortium populations (we hypothesize that population setpoints are a poorly-understood form of dynamic memory).

The fourth TF will integrate research activities using systems-level modeling to establish metrics for the efficient flow of energy and information through an electroassembled bio-electronic network. By physically and computationally linking the components of these TF areas, biohybrid devices are envisioned that open lines of communication between the biotic and abiotic worlds.

Further, the PIs will initiate a new summer school on redox-based bioelectronics and systems and synthetic biology-based design, especially targeting local undergraduate and graduate students, including those from other minority serving institutions. Summer schools will rotate among the three institutions and leverage the respective PIs' expertise and institutional strengths at Maryland (Center for Minorities in Science and Engineering), GT, and Wisconsin (WID Illuminating Discovery Hub) to ensure diverse participation and quantified outcomes.

This project has been jointly funded by Division of Molecular and Cellular Biosciences (MCB) in the Directorate for Biological Sciences (BIO), Division of Computing and Communication Foundations (CCF) in the Directorate for Computer and Information Science and Engineering (CISE), Division of Electrical, Communications and Cyber Systems (ECCS) in the Directorate for Engineering (ENG), and the Division of Materials Research (DMR) in the Directorate for Mathematical and Physical Sciences (MPS).

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.