Electrogenetic communication structures to encode, propagate, and decode information through synthetic biology

Abstract

Cellular communication, the exchange of information between cells, is a process in which cues are encoded, propagated, and decoded through shared chemical and physical semantics. This general process forms the basis for homeostatic decision-making to which the cell dedicates substantial resources. Central to these processes are abstract communication structures each which serve a defined role and create semantic compatibility. “Transmitters” relay messages away from the source, the “channel” propagates the message through a network, and “receivers” are the terminal site of relay. When a particular semantic code of a message is not fit to the structure it must interact with there is a loss in communication capacity. Overcoming this barrier requires transformation of semantic variants to fit the context of a particular communication channel. For bioelectronics, communication structures must interconvert electron-oriented codes, such as current and voltage, into molecularly-oriented codes, such as genetic inducers and molecular gradients. Here, I present the creation of a redox electrogenetic communication channel which contains the principal transmitter, channel, and receiver structures, each of which is made through the combination of electrochemistry, materials science, and synthetic biology. Each of these structures is the focus of separate sections within my dissertation. First, I will present receiver structures that convert molecular information into electrochemical redox signals. These systems are comprised of engineered bacteria that recognize molecular cues and catalytically synthesize redox-active components that are received using electrochemistry. Second, I will present transmitter structures that encode electronic inputs into redox-active inducers that are perceived by genetic circuits. These circuits interact with the message to ensure faithful replication of the message and constitute electrogenetic noise suppression at the single-cell level and second messenger homogenization on the population level. Lastly, I will present channel propagation which links transmitter and receiver structures. These systems link the prior two sections and network communication into a greater context of biological control. I will demonstrate these interactions through controlled production of small molecules, on-demand cell lysis, and restructuring of cell consortia. Together, these methodologies constitute a bioelectronic communication paradigm that can directly mediate information exchange between electronic and molecular formats. Future application of these communication structures will enable logic-driven control systems and computer-learning models in a medical and environmental internet of bionano-things and true cybernetic integration.