About This Program
The mission of the DNA Synthesis Science Program is to enable users to perform state-of-the-art functional genomics research and to help them translate genomic information into biological function. Our strategies are to provide users:
- Access to large-scale DNA synthesis and assembly capabilities
- Access to integrated genome technologies and informatics pipelines — from sequencing data generation and database mining including JGI genome databases (Genome portal; bacteria: IMG; fungi: MycoCosm; plants: Phytozome), to construct design, DNA synthesis, microbial strain engineering, transcriptomics, and high-throughput functional characterization.
Additionally, our value proposition is to enable users to study the function of genes that are otherwise difficult to source from environmental samples, including uncultured microbes and higher plants. For consortium-type projects, we can help coordinate the consortiums to publish articles on the highest impact journals.
Proposals may be submitted at any time as brief white papers and will be reviewed semi-annually.
All proposals will be reviewed for scientific merit, DOE relevance, proposed usage by the applicant/community, and track record of the applicant. Proposers are also encouraged to review Synthetic Biology Internal Review Process guidelines, as insufficient information will delay or potentially defer approval for the proposal.
For questions about the appropriateness of projects, program specifics or technical guidance, please contact Yasuo Yoshikuni (program head) and Miranda Harmon-Smith (project manager). For questions about the application process, please contact Miranda Harmon-Smith.
The DOE JGI DNA Synthesis Science Program is interested in the projects where DNA Synthesis Science enables new paradigms in transforming our understanding of microbial and plant physiology and in harnessing these biological systems for the creation of a green economy.
Among major initiatives of the DNA Synthesis Science Program are:
- Microbes-to-Biomes (M2B), a Berkeley lab-wide initiative designed to reveal, decode, and harness microbes that are relevant to bioenergy supply and environmental protection. Our program focuses on studying biological systems modulated by secondary metabolites. Leveraging our integrated pipeline, we will discover, identify, and characterize these secondary metabolites. We are also developing tools and methodologies to directly engineer microbes isolated from environments and to culture these microbes in various conditions. In the long-term, our goals are to enable engineering soil microbiota to augment their ability for biofertilization, biocontrol, and phytostimulation.
- Genome to Enzymes and Pathways, which focuses on large-scale discovery, identification, and characterization of enzymes and pathways that are relevant to the DOE missions. In collaboration with other science programs, we actively develop bioinformatics tools to mine unique enzymes and pathways involved in lignocellulose decomposition, carbon-carbon bond formation (e.g., CO2 fixation) and breaking reactions, redox reactions, and biosynthesis of plant secondary metabolites through the DOE JGI’s Genome Portals. These enzymes and pathways are subsequently synthesized and biochemically characterized. If needed, combinatorial (mutant) libraries are generated for further characterization.
- Fast-paced metabolic engineering. Metabolic engineering traditionally utilizes a stepwise approach for strain development, requiring cycles of construct design, building, and characterization. In partnership with the Joint BioEnergy Institute (JBEI), we are developing tools including ICE and DIVA (requires password) (requires password) to rapidly design combinatorial construct variations. These constructs are subsequently synthesized and tested for their ability to produce desired chemicals.
DOE JGI Capabilities
The DOE JGI offers the following synthetic biology product types, with the estimated cycle times listed:
- Short size constructs (<1 kb): ~80 calendar days
- Medium size constructs (1-5 kb): ~110 calendar days
- Large size constructs (5-10 kb): ~ 170 calendar days
- Very large size constructs (10-50 kb): ~210 calendar days
- Combinatorial library: ~300 calendar days
Estimated DNA Synthesis Capacity
In FY2015, it is anticipated that approximately 2.1 Mb of DNA synthesis capacity will be available under this program, contingent on satisfactory peer review and the availability of appropriated funds. The program accepts proposals from single investigator as well as consortium-style projects. A consortium can request very large-scale synthesis capacity (50 – 1200 kb). It requires participation of principal investigators from at least three different institutions and a plan to disseminate materials synthesized by the program to the scientific community. A single investigator can request from 50 – 400 kb. If the project requires combinatorial library, the applicants are encouraged to propose research projects requiring up to 2 M bases of DNA synthesis capacity (no cloning and sequencing validations will be carried out for each construct).
Between 5-8 awards are anticipated through each bi-annual call. Awards are expected to begin in as soon as all the approval processes described in the section VI are completed.
On average, we attempt to deliver at least 80-90% of all constructs in each project. Certain sequence characteristics (e.g. homo-polymers, repeats, hairpins and other secondary structures, and high/low local/global GC/AT compositions) should be minimized, because it makes synthesis less amenable.
DNA Synthesis Science proposals are accepted on a continuous basis and will be reviewed twice a year. Submission deadline for reach review process is listed below. Letters of intent are not required.
- January 30, 2017
Synthetic Biology Internal Review
All proposals are subjected to the Scientific Biology Internal Review (SBIR – see here for more details). Each proposal is reviewed by at least three external reviewers. The SBIR encourages investigators to extensively consider broader aspects of their research (e.g., environmental, bio-containment, biosafety, and biosecurity), to evaluate both positive and negative impacts regarding Environmental, Ethical, Legal, and Societal Implication (ELSI) issues associated with the proposal, and to propose strategies to mitigate issues of concern. If the issues of concern are not sufficiently addressed, we will request users to modify the proposal. If the issue is not resolved, the proposal may be rejected. SBIR generally takes three weeks.
Investigators should not merely write “None” or “All research will be conducted in a safe manner according to Federal regulations” in the broader implications statement, as this will lead to the reviewers asking for proposal modifications, incurring three week or longer delays.
Investigators must explicitly state if their proposed research would:
- Demonstrate how to make a vaccine ineffective
- Confer resistance to antibiotics or antiviral agents
- Enhance a pathogen’s virulence or make a non-virulent microbe virulent
- Increase transmissibility of a pathogen
- Alter the host range of a pathogen
- Enable a pathogen’s ability to evade diagnostic or detection modalities
- Enable the weaponization of a biological agent or toxin