The Defense Advanced Research Projects Agency (DARPA) issued a program solicitation for the Simulated Microbial Systems (SMS) initiative, targeting the creation of advanced computational simulations to predict the behavior of Escherichia coli (E. coli). This 18-month program aims to unify recent advances in biological modeling and systems biology to develop a generalizable software platform. With a total funding pool of approximately $15.8 million, DARPA anticipates multiple awards to various performers. Key tasks include innovative experimental workflows for data collection on E. coli, alongside simulations that inform each other. The solicitation entails two primary research thrusts: "Measure & Inform" for data collection and "Simulate & Predict," focusing on creating extensible simulation software. Participants will showcase their progress through structured Capability Demonstrations (CDs) and Pressure Tests (PTs). The program emphasizes the significance of evaluating both molecular dynamics and higher-order behaviors, aiming to establish statistical equivalence between simulation and experimental data. Ultimately, the SMS initiative represents a significant step toward realizing the vision laid out by Nobel laureate Francis Crick regarding the complete understanding of E. coli, laying the groundwork for applications in biotechnology and biomanufacturing relevant to defense interests.

The document outlines guidelines for submitting proposals to DARPA's Simulating Microbial Systems (SMS) program. It emphasizes the importance of forming teams to cover all technical areas and expertise necessary to achieve program goals. Proposals must include a summary of the project overview, team capabilities, and any relevant experience, restricted to unclassified information. Key components to address in the proposals include existing team members’ expertise, institutional resources, unique approaches, and planned metrics. The document highlights the need to identify technical challenges and potential programmatic risks, along with strategies for their mitigation. Budget proposals are capped at $8 million. Additionally, it instructs that submissions be concise, presented in a single PDF slide in landscape orientation, avoiding proprietary content, and illustrating the team structure if relevant. This guidance emphasizes collaboration, thoroughness, and clarity as critical elements of a successful proposal for federal funding opportunities within the scientific community.

The DARPA-PS-25-04 solicitation addresses the Simulating Microbial Systems (SMS) initiative, requiring abstracts for proposals that adhere to specific formatting and content guidelines. The abstract must be submitted in a standard format, including a title page, an executive summary, a proposed approach, identified technology challenges, technical ability claims, estimated costs, and references. The executive summary is limited to one page and should articulate the technical problems SMS aims to resolve in the proposer’s own words. The proposed approach section must detail the techniques and innovations applicable to the challenges outlined, while the technology challenges must highlight the risks associated with the proposal. The technical ability section must justify the team's qualifications and past experience relevant to achieving SMS goals. Additionally, the estimated cost must be presented, with total funding requests not exceeding $8 million. This document outlines a structured process for submitting competitive proposals aimed at advancing the understanding and application of microbial systems, emphasizing the importance of original insights and thorough documentation of competencies and cost projections.

This document outlines an Other Transaction Agreement (OTA) between DARPA and a performer for a research and development program aimed at prototype development. It emphasizes that proposers can suggest edits to the model OTA, although such edits will not influence the evaluation. Key sections include the scope and objectives of the agreement, project management responsibilities, payment obligations, and terms regarding patent and data rights. The agreement stipulates that the performer is responsible for reporting milestones and managing technical execution while DARPA retains oversight and certain data rights. It mandates adherence to cybersecurity standards, particularly regarding Covered Defense Information (CDI), and prohibits contracting for specific telecommunications equipment that poses national security risks. The agreement is structured to facilitate innovation while ensuring government interests are safeguarded through defined rights and responsibilities, ultimately fostering successful collaboration in developing critical technologies.

The document provides detailed instructions for preparing a cost proposal using a specific spreadsheet template intended for federal RFPs and grants. Organizations must complete essential tabs, including TOTAL and Budget by Milestone, while maintaining existing formulae to ensure accurate calculations. The cost proposal must encompass various categories such as Direct Labor (DL), Fringe Benefits, Overhead, Subcontracts, Consultants, and Other Direct Costs (ODCs), which should each be further itemized. The proposal requires a comprehensive breakdown of materials and supplies, equipment, travel expenses, and general administrative costs. Moreover, it includes provisions for detailing subcontractor and consultant activities, supported by documentation. The document emphasizes accuracy, thorough justification, and the importance of meeting submission requirements to avoid delays in award processing. Ultimately, the guidelines aim to streamline the proposal process while ensuring compliance with governmental standards, reflecting the rigorous expectations associated with federal funding opportunities.

The document outlines a schedule of milestones and payments for a federal initiative focused on simulation and experimental data analysis. Proposers are instructed to complete a spreadsheet detailing their proposed milestones, deliverables, and associated payments, following the framework provided. Key milestones span from Month 0 to Month 18, including critical tasks such as the development of data sharing plans, baseline simulation codes, and various reports verifying adherence to biological properties. Specific activities include the creation of technical documentation, delivery of experimental data for validation, and participation in workshops to discuss progress with stakeholders. Note that certain sections marked "highlighted" should not be completed by proposers. This structured approach ensures accountability and transparency in the project, aligning with federal RFP standards, and serves to facilitate collaboration between multiple teams involved in the research effort.

The Simulating Microbial Systems (SMS) program, managed by Dr. Christopher Bettinger at DARPA, aims to develop advanced, physics-based simulations to predict the behavior of microorganisms, particularly bacteria. By enabling in silico experiments, the program targets the acceleration of biomedical research, assessing pathogen threats, and predicting the effectiveness of medical countermeasures. The guidelines outline the handling of Controlled Unclassified Information (CUI) within this program and detail compliance with federal regulations, including the Freedom of Information Act (FOIA). Key areas include the identification and protection of sensitive information, operations security (OPSEC) measures, and the categorization of information regarding controlled technical and proprietary business elements. The guide emphasizes that all personnel involved with the SMS must coordinate disclosures of information and manage data carefully to prevent unauthorized access. Ultimately, this effort ensures that relevant stakeholders in the Department of Defense have necessary access to critical simulation software and data to inform the security landscape and generate practical biomedical solutions.

The DARPA request for proposals (RFP) outlined in document DARPA-PS-25-04 focuses on the Simulating Microbial Systems (SMS) program, emphasizing the integration of wet lab experiments and computational simulations to enhance microbial modeling. Two primary thrusts are identified: 1. **Measure & Inform**: Proposers must detail methods for guiding experimental designs and simulations, addressing data gaps, ensuring accuracy and precision in data collection, and managing run-by-run variations in experiments. 2. **Simulate & Predict**: This thrust requires elaboration on simulation methodologies, computational modeling, and how simulations can effectively forecast cell behaviors, capturing variations in wet lab experiments while minimizing measurement errors. Further expectations include a cohesive workflow between the two thrusts, innovative improvements in modeling, and a robust plan for data storage and sharing. Use cases covering biomanufacturing and antimicrobial efficiency must be addressed alongside metrics for verifying simulation equivalency to experimental results. Plans for interaction with government teams, risk management, and adherence to Controlled Unclassified Information (CUI) protections are also critical. Overall, the RFP seeks proposals that advance microbial systems modeling through interdisciplinary collaboration and innovative approaches.