NSF X-Labs Initiative: Sequence to Function

To:	Associate Deans for Research; College/School Research Administrators
From:	Office of the Vice Chancellor for Research
Date:	October 21, 2026
Subject:	NSF X-Labs Initiative: Sequence to Function

Deadline

Deadline for Internal Review:

November 23, 2026

Project Description

Although recent advances allow us to predict the static structure of proteins, we lack insight into their dynamic behavior. Even in minimal cells, the function of many genes and proteins remains unknown. NSF X-Labs in this space will close that gap by creating platform technologies that enable the intentional design of individual proteins or entire genomes whose function is predictable and/or controllable. Teams will pioneer and integrate advances in protein design/synthesis, genome assembly, synthetic cells, or experimental functional discovery and validation. Additionally, NSF X-Labs might use super intelligence (SI) to dramatically accelerate our ability to engineer the behavior of designed proteins or synthetic cells, including their metabolic requirements, stability, functional outputs, by-products, or system-level interactions.

An NSF X-Labs Mission in this Topic must be transformative, accelerating breakthroughs in our understanding of the relationship between sequence and function, and catalyzing capabilities to engineer proteins or entire genomes with exceptional new capabilities. Successful teams will develop platform technologies, demonstrate measurable impact on the U.S. biotechnology landscape, and position their technologies for widespread use by overcoming technical barriers that limit implementation and investment. Although NSF X-Labs in this space will have widespread applicability, each team should identify 2-3 high-utility domains and should eventually establish projects in them. Teams proposing to this topic should identify how their approach to biosafety and biosecurity is tailored to their Mission and its pilot application domains including an assessment of dangerous gain-of-function and an accompanying plan to mitigate unintended consequences.

NSF anticipates awarding selected teams a 9-month Phase 0 with a Go/No Go selection period beginning after 7 months. NSF anticipates awarding teams selected for Phase 1 an approximately 24-to-36-month period of performance with the intention of renewing high performing teams for Phase 2 following subsequent Go/No Go selections.

Please note that this internal competition pertains only to the X-Labs: Sequence to Function opportunity. An internal competitions for the X-Labs: Computation at the Limit of Physics opportunity will be issued separately upon NSF’s release of a Topic Announcement in that area.

Amount per Phase 0 Award: $1,500,000
Duration of Phase 0 Award: 9 months

 

Eligibility

UW-Madison may submit two Phase 0 proposals as lead organization.

Please note: Each department may nominate one researcher for the NSF X-Labs Initiative: Sequence to Function internal competition. Applications submitted to OVCR must include a statement that the PI’s department chair has reviewed and approved the application as the department’s sole submission for this internal competition.

Website

The following link contains additional information on the program and specific application instructions:
https://sam.gov/workspace/contract/opp/4da70f039bbc4e2fbddce36bc55ab394/view

Internal Competition Application Instructions

Sponsor Deadlines

Applications are due to National Science Foundation by February 08, 2027.

Questions?

Contact grants@research.wisc.edu.