Leader: Tanja Kortemme

The most basic unit in the design of synthetic biological systems are parts – pieces of DNA, RNA, or protein that encode and/or can carry out a defined biological function(s) – binding to another molecule or catalyzing a reaction. Parts can be assembled in combination to make devices that carry out more complex functions. Thus, a core thrust of SynBERC is the design and manipulation of standard biological parts. Over the last year, researchers in the Parts Thrust have focused on:

• the development and characterization of new parts,
• the development of methods to computationally design or improve parts, and
• improvement in methods to assemble parts into systems.

The goal of this thrust is to develop a large set of parts with specified properties that can be functionally linked together for the construction of complex biological systems.  Thus, the specific aims of this thrust are (i) to collect a large repository of parts, (ii) to quantitatively characterize the functional specifications of these parts, (iii) to redesign or modify these parts for new or optimized functions, and (iv) to optimize parts composability.
Many classes of parts are necessary to build complete biological systems, such as those targeted in our testbed examples.  Below are the major classes of parts that we plan to collect in the repository, either through “harvesting” parts that already exist in nature, or by designing new, synthetic parts.  Although broad, even this initial list is not meant to be representative of all types of biological parts:

• Expression control parts: Elements that control the synthesis of genetic components. This includes transcriptional elements such as promoters and their cognate DNA binding proteins and translational elements including ribosome binding sequences, riboswitches, and 5’ or 3’ UTR elements that could control either transcription or translation.
• Degradation parts: Elements that control the degradation of genetic components – both mRNA degradation, and  protein degradation (degrons). 
• Sensors: Receptors and transmembrane molecules that are able to detect and transmit stimuli from the external environment. 
• Post-translational regulatory parts: Molecules involved in regulation and signaling.  These might modulate the state of other components, either positively or negatively, as in the case of kinases and phosphatases.
• Transporters: Proteins that facilitate the transport of other molecules through the cell membrane.  This class includes passive channels and pumps/antiporters.
• Metabolic enzymes: Enzymes that carry out chemical rearrangements and that can be used for steps in the synthesis of particular chemical product.
• Adhesion/targeting parts: Molecules that anchor or target the cell in a particular place in the external environment.
• Mechanical/structural parts: Molecules that direct complex formation and higher order physical assembly.

SynBERC researchers are using the Registry of Standard Biological Parts to define and describe all basic parts already in use or parts that are being newly designed.  Because information in the Registry is web-accessible, all parts are available both within and beyond the Center. Based on on-going research, small numbers of new parts for each type (above) are being generated on a continuous basis. However, in some cases it is useful for the Center to focus its resources in order to quickly produce a comprehensive set of parts of a particular type (e.g., a dozen independent DNA binding proteins, or all the enzymes involved in the alkaloid biosynthetic pathway). In all cases, SynBERC is maintaining collections of the DNA encoding parts.  Also, in cases where de novo DNA synthesis is used to construct new open reading frame-based parts, SynBERC researchers are adding a barcode signature to identify the ORF as being a standard SynBERC part (see BioBricks Barcodes). By signing our designed DNA, SynBERC is helping to establish a culture of accountability in synthetic biology (e.g., responsible engineers sign their work), and provide a standard site that can be used for the rapid PCR-based detection of the presence or absence of our parts in an uncharacterized sample. By embedding detection features into synthetic biology technology from the beginning, we are working to preemptively avoid imaginable future biological risks.