General inquiries about the program
- Technical/Scientific Program Contact: Questions regarding the specific program areas/technical requirements can be directed to both a program head, Yasuo Yoshikuni, and a program manager, Miranda Harmon-Smith.
- Administrative Contact: Questions about program rules should be sent to the program manager, Miranda Harmon-Smith.
The vision of the DOE JGI, as set forth in its 10-year strategic vision, is to serve community science as a user facility pioneering functional genomics to solve the most relevant bioenergy and environmental problems. 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 (up to 500 K bases/proposal for independent PIs and 1.5 M bases/proposal for consortiums)
- 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 provide project management and help coordinate the consortiums to publish articles on the highest impact journals.
Specific Focus Areas
The DOE JGI DNA Synthesis Science Program is interested in the projects where DNA Synthesis Science enables new paradigm in transforming our understandings of microbial and plant physiology and in harnessing these biological systems for the creation of green economy.
Among the major initiatives of the DNA Synthesis Science Program are:
- Microbial and Plant Systems Modulated by Secondary Metabolites, secondary metabolites are often involved in communications among biomes. Therefore, our program focuses on discovery, identification, and characterization of these secondary metabolites, leveraging integrated pipeline including sequence data mining, construct design, synthesis, and assembly, and high through-put/resolution mass spectrometry. 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 facilitate understanding and engineering soil microbiota to augment their ability for bioenergy supply and environmental protection.
- 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 proprietary 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) to rapidly design combinatorial construct variations. These constructs are subsequently synthesized and tested for their ability to produce desired chemicals.
Estimated DNA Synthesis Capacity
In FY2015, it is anticipated that approximately 2.1 M bases 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 for consortium-type and independent-type projects. The consortium-type project can request very large-scale synthesis capacity (50 K bases – 1.5 M bases). 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. The independent-type project can request large-scale synthesis capacity (50 K bases – 500 K bases). There is no restriction in team composition and material sharing. 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.
The DOE JGI reserves the right to fund, in whole or in part, any, all, or none of the proposals submitted in response to this program.
Maximum and minimum award size
The award size will depend on the number of meritorious proposals and the availability of appropriated funds.
Independent-type project: ceiling 500K bases: floor 50K bases
Consortium-type project: ceiling 1.5M bases: floor 50K bases
Although the floor for both project types is 50 K bases, we encourage each proposal to request > 80% of each capacity.
Expected Number of Awards
The DOE JGI anticipates making 5-8 awards under this program. The exact number of awards will depend on the number of meritorious applications and the availability of appropriated funds.
Anticipated Award Size
The DOE JGI expects the typical award size of DNA synthesis capacity will be 320 – 500 K bases for independent-type project and 960 K – 1.5M bases for a consortium-type project over one year. Applicants are encouraged to propose research projects requiring 320-500 K bases of DNA synthesis capability for independent-type project and 960 K – 1.5 M bases of DNA synthesis capability for consortium-type project. 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). In 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.
Period of Performance
The DOE JGI anticipates synthesized constructs are delivered:
- 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
following the project initiation call.
Both US and international academic institutes (universities, government labs, and others) and companies are eligible to apply.
Each Principal Investigator may submit up to two proposals per semi-annual competition.
Cost sharing is not required.
In the proposal, we require all applicants to fill in the below sections and submit through the WIP web system:
Semiannual DNA Synthesis Call
Please state a title of your project proposal within 255 characters including spaces. The title should be technically informative.
- DOE mission relevance
Please select the area(s) of DOE mission relevance appropriate to your proposal from Bioenergy, Biogeochemistry, Bioremediation, Carbon cycling, and Phylogenetic diversity.
- Total request in kb
In general, each construct comprises regions account for an insert and a plasmid. Please state the total size of inserts requested in the proposal. If the plasmid also needs to be synthesized or modified, please include the size of the plasmid once in the total size requested.
- Number of constructs for each product
Please state the number of inserts and/or plasmids requested for synthesis and/or modification according to their sizes: Short (<1 Kb): Medium (1-5 Kb): Large (5-10 Kb): Very Large (10-50 Kb): and combinatorial.
Please answer the following questions by Yes or No
Are any of the genes or fragments to be synthesized:
- Related to the pathogenicity of an organism?
- Known to or shows a potential to encode any form of infectious agent or viral life-cycle component?
- Known to have any toxicity or the likelihood that this project might increase toxicity?
- Intended for use in creating a vaccine?
If you answered ‘Yes’ to any of the above questions, please state the reason.
Please briefly describe the high-level goal of the project, the relevance of the research, why it requires DNA synthesis, and how you plan to use the constructs once you receive them (3,000 characters including spaces).
Please briefly describe the scientific rationale for performing this work (3,000 characters including spaces).
- Technical info
Please briefly describe technical information for constructs to be synthesized, the design strategy, codon optimization (if any), vectors, technical challenges, source of sequence information (databases and organisms), estimated schedule for delivering sequence files and vectors to JGI (3,000 characters including spaces).
- Preliminary data
Please briefly describe preliminary data to support your proposal if there is any (3,000 characters including spaces).
- Biosafety, Biosecurity, Biocontainment, and Environment
Please describe the Biosafety, Biosecurity, Biocontainment, and Environment aspects of your proposed research, including both the current aspects and the long term implications of the work (desirable or otherwise). Describe what you will do (and who you will collaborate with) to address any aspects of concern and how you will mitigate any undesirable outcomes. This information will be critically assessed during the JGI’s Synthetic Biology Internal Review Process and your research will be delayed if the reviewers request modifications to your proposal due to insufficient consideration or description of these aspects (3,000 characters including spaces).
- Lay Description
The JGI reviews all synthetic biology proposals for ethical, legal, and social implications (ELSI), as well as bio-security, bio-safety and environmental safety. Some of our reviewers have been selected because of their ELSI expertise, and may not be familiar with some scientific jargon. In order to facilitate a better understanding of your proposal for these reviewers, please provide a lay description of your proposal (excluding jargon), so that non-scientific/technical experts can better assess the broader aspects and implications of the work in the context of the research that is proposed to be done (3,000 characters including spaces).
- Team composition and responsibilities
If the project is part of collaboration, please state the roles and responsibilities of each team member (3,000 characters including spaces).
- DOE mission
Please briefly describe the relevance of this research to DOE Missions and goals (3,000 characters including spaces).
Please add contact information for any additional Co-Principal Investigators or collaborators other than yourself. If you are not the primary contact for materials, please include one.
Please upload CVs for Principal Investigator and Co-Principal Investigator (required). We also encourage you to upload additional supporting files for your project, including letters of support, figures, tables, prior publication, etc. If uploading sequence files intended for synthesis, please use annotated GenBank format. Limit 10 documents total.
All proposals are evaluated based on technical feasibility of the project by at least one scientist in the Synthetic Biology Group at the JGI. The Scientist evaluates whether the construction of each construct requested is technically feasible through our standardized synthesis pipeline. Some proposals are rejected at this stage, because they do not conform to our synthesis pipeline. Users are encouraged to minimize the presence of certain sequence characteristics (e.g. homo-polymers, repeats, hairpins and other secondary structures, and high/low local/global GC/AT compositions) should be minimized in each construct, because the presence of these secondary structures makes synthesis extremely difficult and time-consuming. Technical Review process usually takes four weeks.
Synthetic Biology Internal Review (SBIR)
All proposals are subjected to the 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
- How does the DOE JGI DNA Synthesis Science Program treat intellectual property right?
Please see our general user agreement for more information.
We follow the United States patent law to determine the inventorship of the JGI scientists involved in each project based on his/her contribution to the conception of the claimed invention.
For licensing and partnership, we follow the policy of Innovation and Partnership Office at Lawrence Berkeley National Laboratory.
- Does the DNA Synthesis Science Program evaluate proposals submitted from industrial applicants differently?
No, we do not. We evaluate proposals submitted from both industry and academic applicants based on the criteria discussed in Section V. A-B. However, industrial applicants are encouraged to discuss plans for writing publications (including publication records) and disseminating materials synthesized by the program.
- What is the difference between the JGI DNA Synthesis Science Program and commercial synthesis providers?
Our goal is to enable users to perform state-of-the-art functional genomics research, to transform our understanding of microbial and plant physiology, and to harness these biological systems for the greater economic good.
Beyond basic DNA synthesis, we provide users access to:
- Large-scale DNA synthesis that other public and/or private funding sources cannot support,
- The JGI’s integrated DNA Synthesis Science pipeline, and
- Project management (consortium projects only).
- What is the difference between natural products and secondary metabolites?
Both terms, natural products and secondary metabolites, are often utilized in the similar fashion. The DOE uses the standard definition of ‘secondary metabolites’, metabolites that are not essential to the normal life of an organism. The DOE supports the investigation of its mission-relevant biological systems that are modulated by secondary metabolites derived from microbes and plants. However, natural products are also often associated with studies relevant to the medicine and human health such as antibiotics discovery, and these studies are out of scope for the DOE mission relevance. To avoid any confusion, we strictly use the term, secondary metabolites.