892431-26-RFI-0003 Attachment.pdf

DEPARTMENT OF ENERGY

Request for Information (RFI) on Identifying Basic Research Challenges to Accelerate United States Biotechnology

Leadership

THIS IS A REQUEST FOR INFORMATION (RFI) ONLY for the purpose of conducting market research and does not constitute a solicitation or a promise to issue a solicitation. Responses are voluntary and will be used to inform strategic planning, program design, and future funding mechanisms.

AGENCY: Office of Science, Department of Energy RFI Number: 892431-26-RFI-0003 Issue Date: September 24, 2026 Response Due: October 15, 2026

SUMMARY: The Biological and Environmental Research (BER) program within the United States (U.S.) Department of Energy’s (DOE) Office of Science (SC) has a pioneering legacy in genomic research, having famously co-initiated the landmark Human Genome Project in 1990 to study the genetic impacts of radiation exposure. BER has since funded fundamental systems biology research ranging from molecules to microbes to plants in the context of their broader environment. By translating genetic blueprints into predictive models of biological systems, BER research aims to develop biomass feedstocks and bioproducts, clarify complex biogeochemical cycles, and design novel biotechnological breakthroughs in support of the U.S.

bioeconomy. These genomic efforts are accelerated by world-class user facilities and specialized computational platforms, such as DOE’s Joint Genome Institute, Environmental Molecular Sciences Laboratory, and Systems Biology Knowledgebase.

Even though historical investments have successfully established genomics-enabled biology as a pillar of DOE-BER research, the transition from observing and analyzing biological systems to actively designing them through biotechnology needs to be accelerated. This shift toward broader biosystems design science leverages a fundamental genomics-based understanding of biology to solve complex challenges in the production of bio-advantaged fuels, chemicals, materials, and bio-based processes.

The DOE’s Genesis Mission and recent advances in artificial intelligence and laboratory automation have opened up possibilities to use the vast amount of data in BER’s research portfolio for developing foundational models to speed up the design-build-test-learn cycle in designing biomolecules, cells, microbiomes, and complex organisms (i.e., plants) with beneficial traits and functions on demand. Interdisciplinary Genesis Mission National Science and Technology Challenges provide a powerful opportunity to supercharge biotechnology advances through (i) rapid collection of data on molecular biological structures in their native environments; (ii) modeling that bridges kinetic, atomistic, and physics-based modeling to capture the dynamics of cells and complex biological systems; and (iii) driving biosystems design to rapidly meet desired manufacturing objectives. BER’s basic research may build biosystems design upon three basic science objectives:

1. Molecules/Proteins to Function: Translating genetic code and macromolecular structures into predictable, biochemical functions.

2. Mastering the Cell: Designing cells, intercellular communication, and metabolic and signaling pathways to control systems-level cellular operations for tailored purposes.

3. Predictive Phenomics: Developing quantitative experimental and multi-scale computational models to predict how plants and microorganisms perform and interface with their environments.

The Genesis Mission will furthermore drive and incentivize the acceleration of biotechnology breakthroughs through a strong emphasis on cross-agency partnerships and strategic collaborations with commercial technology partners.

Input is sought from a wide variety of stakeholders, including:

Educational institutions, DOE National Laboratories, private industry, and philanthropic organizations who can provide input on how to overcome the scientific challenges of using biotechnology to predictively design molecular, microbial, plant, and cell-free systems for the synthesis of bio-advantaged fuels, chemicals, and products important to DOE’s energy mission.

Other Federal agencies that have an interest in collaborating on efforts for biosystems design.

Think tanks and other research organizations that can provide input on how to drive fundamental scientific discoveries closer to commercialization.

To help guide future program development and investments, DOE invites succinct responses to any of the following questions. These responses, together with a Biotechnology Workshop planned for later in 2026, will aid BER’s basic science priorities to address targeted biotechnology and biosystems design objectives.

Category A: Fundamental Science & Biodesign Goals

1. In the context of the three grand challenges listed above, what are the most significant near-term (3–5 years) scientific bottlenecks preventing the transition from descriptive biological observations to predictive, engineering-focused biosystems design?

2. What key capabilities are missing in our current ability to achieve scientific breakthroughs in these grand challenges and/or to scale biosystems design principles from single molecules/proteins to functional cells and whole organisms?

Category B: High-Priority Biotechnology Applications

3. Within the realms of biomolecular structure, proteins, microbes/microbiomes, and plant systems, which specific target areas hold the highest potential for industrial breakthroughs and public benefit?

Category C: Partnerships and Collaboration

4. What models of public-private partnerships, cross-agency cooperation, or leveraging of Genesis Mission activities would be most effective for biosystems design and industrial translation?

DOE reserves the right to use any information submitted by, or obtained from, an interested party in any manner DOE determines appropriate including a public posting of a summary of comments at BER Community Resources | U.S. DOE Office of Science (SC).

Interested parties should not include any classified, business confidential, or proprietary information in their responses. DOE will have unlimited rights in all submitted information.

DOE looks forward to engaging with the community, industry, academia, and other interested parties in a transparent and collaborative manner throughout the process.

Submission Instructions: Responses should not exceed two pages. Please include the name of the organization and the point of contact. Responses should be in a machine-readable PDF format, be submitted as a single PDF attachment to Biotech.Input@doe.gov, and include “Identifying Basic Research Challenges to Accelerate U.S. Biotechnology Leadership” in the subject line of the email.

FOR FURTHER INFORMATION CONTACT: Questions may be addressed to the

DOE Office of Science through Biotech.Input@doe.gov.

BACKGROUND INFORMATION: BER 2026 reports from the Frontier Science for the Bioeconomy Workshop Series can be found in the following links:

Microbial Design for a Developing Bioeconomy Workshop Report Engineering Microbial Communities Workshop Report Plant Design for a Developing Bioeconomy Workshop Report Resilient Crop Production for the Bioeconomy Workshop Report