Leader: Christopher Voigt

A synthetic biological device is an engineered genetic object that produces a human-defined function under specified conditions. Devices are produced by combining one or more standard biological parts. Devices must provide for their reliable physical and functional composition with other devices so that many devices can be readily combined to produce higher order functions.  In theory, an infinite number of devices could be engineered, each slightly different. Individual investigators tend to produce many ad hoc devices in response to the needs of different applications or interests.  To practically complement this tendency and lay the foundation for “plug and play” genetic devices, we must define a reduced set of standard devices families.  Moreover, for each device family, we must also develop a model-backed family-wide specification of the performance requirements that individual devices must satisfy in order to be considered valid devices. 

The Devices and Device Composition (DDC) thrust was initiated with four long-term goals:

• to enable the engineering of a prescribed set of standard devices by developing formal definitions of device families, including family-specific device boundaries and device-device signal carriers,
• using computational modeling and practical experience, to define standard levels for inter-device coupling,
• to design and build devices needed by our testbed applications, and
• to develop and promulgate standard analytical, computational, and experimental methods that support the design, fabrication, characterization, and tuning of reliable, functioning devices.

Now in our third year, we are pursuing important changes in the scope and organization of the DDC thrust’s work. Specifically, we are transferring primary responsibility for the production of testbed devices to the testbeds themselves. The DDC thrust will continue to directly support testbed device engineering via the development of device family specifications as well as foundational methods and tools. Next, the DDC thrust will “reach down” into the Parts and Parts Composition thrust, by taking more direct responsibility for how parts might be engineered to better support composition into devices. Finally, we will be expanding the DDC thrust’s emphasis on measurement and modeling, noting our ongoing need to participate in the creation of a professionally-staffed production facility for producing many, high quality synthetic biological devices (aka, a BioFAB). 

Device Families
A device family is a set of devices that are designed for use in combination with one another. Use-in-combination requires that devices are physically and functionally compatible. Physical compatibility requires that the material encoding and instantiating the devices can be connected. Functional compatibility requires that the signal carrier(s) between devices is independent of the internal workings of each device, and that the signal levels and timing between devices are matched. Because devices are collections of parts that perform human-defined functions (above), there are as many possible families of devices as can be invented. Here, we will focus on those device families that we believe will be most generally useful to the development of synthetic biology:

• Gene expression devices: An existing family of devices that send and receive signals as levels of gene expression, or that process information and materials via the regulation of gene expression.
• Post-translational devices: A proposed family of devices that send and receive signals via the state of enzymes that modify proteins (e.g., protein kinases), or that process information and materials via the regulation of protein state or location (e.g., nuclear export).
• Cell signaling devices: An existing family of devices that send and receive information from one cell to the next via small molecules, peptides, nucleic acids, or other chemicals. As currently defined, cell signaling devices often include device-specific sender and receiver units that convert device-specific signal carriers (e.g., N-Acyl homoserine lactones) into device-independent signal carriers (e.g., gene expression level).
• Metabolic and material devices: A proposed family of devices that process or manipulate chemicals and materials. Metabolic and material devices will accept device-independent signals from other device families (e.g., gene expression), but provide device-specific control of chemical (and other) signals (e.g., metabolic feedback).

SynBERC researchers are working to develop and define these and other useful device families such that individual devices from the same family can be re-used in combination with one another. We have already begun to make good initial progress on describing “gene expression” and “cell signaling” devices. Canton et al presents much of our early work, including a first “datasheet” for a formally engineered synthetic biological device (“formal” in the sense that the device interacts with other devices via a common signal carrier, and is itself assembled from standardized biological parts).  Additional examples of recent accomplishments include modeling, analysis, and preliminary specification of gene expression device signal levels (R. Shetty, MIT Dissertation, 2008), scaffold-based approaches to developing enhanced biosynthetic devices (J. Dueber et al., UC Berkeley, Nature/Biotechnology, submitted), and engineered phosphoregulation of nuclear cytoplasmic shuttling in yeast (S. Sutton, MIT Dissertation, 2008; and submitted).