One of Synberc’s four primary research efforts is the design, construction and manipulation of standard biological parts.
Leader: Tanja Kortemme
University of California, San Francisco
School of Pharmacy, Department of Bioengineering & Therapeutic Sciences
A part is the most basic unit in the design of synthetic biological systems. Parts can be DNA, RNA, or protein molecules that encode and/or carry out a defined biological function – such as binding to another molecule or catalyzing a reaction. Parts can be combined to create devices that carry out more complex functions.
For this effort, the overall objective is to develop parts with specified properties so that they can be combined to others for the purpose of engineering biological devices and systems. PARTS projects pursue these interrelated goals:
• To develop foundational methodologies, both for the design of parts and for parts construction and assembly;
• To engineer and characterize new parts; and
• To redesign existing parts for greater efficiency, including the design of parts families with a range of tunable specifications.
Models and computational tools. Synberc has developed several computational models for designing and optimizing parts, which have been integrated into tools for designing biological systems. These tools include the ribosome binding calculator [ref], structure-based computational part design [ref]. and the Clotho platform that supports all synthetic biology software efforts [ref].
Translational research. The Parts thrust has developed methods that have been useful in non-Synberc labs, as well as in industry. For example, several Synberc and non-Synberc industry partners have licensed the RBS calculator. It has been incorporated into Vector NTI, Life Technologies’ molecular biology software. In addition, the Synberc BIOFAB’s collection of parts is leveraged in the design and assembly of genes within DNA2.0’s Gene Designer software.
Portability of parts into different organisms and contexts. Synberc researchers are exploring develop applications for human health by moving from laboratory organisms to mammalian cells. For example, the Silver lab at Harvard Medical School is developing synthetic sensors for hypoxia and memory circuits in mammalian cells. In addition, the Voigt lab at MIT has developed a system of “genetic wires” that are linked to computational optimization methods. [ref
Automated construction and design. A key bottleneck in the development of functional parts that work predictably in different organisms/contexts has been addressed by Synberc researchers in the Anderson lab at UC Berkeley, who have created standard protocols for the automated construction of devices. Additionally, the Weiss lab at MIT has developed a framework to rapidly assemble and deliver large-scale genetic circuits into mammalian cells
Parts with new functions. Synberc researchers are building and refining biological parts with new functions, including affinity-based oxygen sensors [ref], detectors of key metabolic intermediates [ref - Keasling], and parts that use light as a signal to perform specific actions [Levskaya, A., O. D. Weiner, W. A. Lim, and C. A. Voigt. 2009. Spatiotemporal control of cell signaling using a light-switchable protein interaction. Nature 461:997-1001.]