The new BIOFAB: International Open Facility Advancing Biotechnology (BIOFAB), with two years of funding from NSF and matching support from founding partners, Lawrence Berkeley National Laboratory (LBNL) and the BioBricks Foundation (BBF), aims to produce thousands of free standardized DNA parts to shorten the development time and lower the cost of synthetic biology for academic or biotech laboratories.
Of the estimated 3,500 critical control elements in an E. coli bacterium, fewer than 100 have been seriously studied and characterized. Of the 500-plus promoters listed in current registries, for example, fewer than 50 have been measured.
BIOFAB is raising additional funds to hire 29 full-time staff who will systematically refine, standardize and characterize the activity of each genetic control element in E. coli, so that large-scale collections of genetic parts can be treated more like standardized components. What the researchers learn will be applied to parts collections in other microbes and used to assemble engineered biological systems.
BioFab projects will be designed to produce broadly useful collections of standard biological parts that can be made freely available to both academic and commercial users, while also enabling the rapid design and prototyping of genetic constructs needed to support specific needs of partner efforts such as SynBERC Testbeds. The BioFab will thus also represent the first significant focused investment in the development of open technology platforms underlying and supporting the next generation of biotechnology. Once fully operational the BioFab facility will be capable of producing tens of thousands of professionally engineered, high quality standard biological parts each year.
The Central Dogma (C-dog) project aims to design, build, and characterize a collection of ~6,000 standard biological parts necessary to control key aspects of genetic expression in a select number of organisms. This parts collection, to be known as the “C. dog.” collection, will support the scaleable rational engineering of the central dogma in E. coli and S. cerevisiae. More specifically, we will design, build, and test a collection of engineered genetic components that control DNA replication, constitutive RNA production, RNA processing and degradation, translation initiation, and protein degradation. For each class of functional genetic element, we will engineer and validate a full suite of specific elements.
As one example, in the case of bacterial transcription terminators, we will develop a set of terminators at each decade of termination efficiency (i.e., 0, 10, 20, 30 … 80, 90, 100% termination efficiency) using a combination of semi-rational library design and experimental screening. For each termination efficiency level, we will validate and document 10 sequence distinct terminators (i.e., ten different DNA sequences each encoding a transcriptional terminator that operates at 50% efficiency, et cetera). Being able to provide for multiple sequence distinct instances of specific genetic functions is essential in order to obtain reliable performance of integrated genetic systems across evolutionary times scales; frequent reuse of identical sequences in early synthetic biological systems leads to unintentional instability of many component genetic constructs due to direct sequence repeats.
SynBERC parts on demand
The BIOFAB is working closely with the Synthetic Biology Engineering Research Center (SynBERC) to develop parts and devices as requested for SynBERC testbed applications. We will make available a standing rapid prototyping service to all SynBERC researchers so that any needed engineered genetic systems can be quickly and effectively designed, assembled, and tested.
Bio-Fabrication and Human Practices
The BIOFAB — along with the field of synthetic biology as a whole — promises significant engineering advances in the design and composition of living systems. It also represents a practical exercise in the capacities and limits of a parts-based approach to biological engineering—organizationally, commercially, and biologically. In this way, the BIOFAB is an ideal testing ground for a range of human practices questions currently in circulation. Many of the security analysts, bioethicists, science studies practitioners and others studying synthetic biology have calibrated their work to the promises and dangers of making biology easier to engineer and making materials and know-how more widely available. To the extent that the BIOFAB successfully achieves its goals it is likely, in short, to ramify across multiple domains. In such a case, as its developers have recognized, the question of how the BIOFAB is organized and orchestrated becomes all the more pressing.