ONHS Report: DARPA-PA-25-07-06

Selective Harnessing of Intrinsic Neuroplasticity Engineering (SHINE)

Solicitation ID: DARPA-PA-25-07-06

Agency: DARPA/DSO

Type: Solicitation

Deadline: 2026-10-09T16:00:00 ET

Eligibility: Maybe (Team Member/MIPR)

Funding: Limited to $2,000,000 per award

Doc Type: BAA

Clearance: CUI

Program Manager: SHINE@darpa.mil

Last Updated: 2026-08-29 16:03

Analyzed File: DARPA-PA-25-07-06.pdf

Eligibility Reasoning

DARPA, under this solicitation, will not award separate contracts to FFRDCs as prime or subawardees but will instead leverage their existing sponsors' agreements. ... Proposals that include a ... FFRDC ... as a subcontractor may also be deemed non-conforming unless ... cost proposals must exclude their funding, as DARPA will not fund them through the prime.

Note: This is an AI-generated summary...

Summary

The Defense Advanced Research Projects Agency (DARPA) seeks proposals for the Selective Harnessing of Intrinsic Neuroplasticity Engineering (SHINE) program. The objective is to develop and demonstrate prototype systems capable of inducing neuroplasticity with spatial and temporal precision within specific neural circuits, addressing the limitation of current methods that engage plasticity broadly. This 18-month, proof-of-concept effort aims to establish the feasibility of selectively modifying intended neural substrates while minimizing off-target effects. The program is divided into two tracks: Track A (Accelerated Translation) for integrating clinical-ready systems with a path to human application, and Track B (Foundational Technology Development) for high-risk, novel approaches like synthetic biology or engineered cells. All proposals must demonstrate a chain of evidence for intervention selectivity, biological target engagement, and selective neuroplasticity. Awards will be up to $2,000,000 in the form of an Other Transaction (OT) agreement. Excluded research areas include non-targeted systemic drugs, isolated physical neuromodulation, solely behavioral therapies, and invasive surgical implants.

Overall Technical Areas

Targeted NeuroplasticityMolecular EngineeringSynthetic BiologyCellular EngineeringPrecision NeuromodulationBiomaterial-Based DeliveryNeural Circuit TargetingBiological Target EngagementQuantitative Neuroscience AssaysNeuroimaging and BiomarkersElectrophysiological AnalysisIn Vivo Animal ModelsIn Vitro Brain ModelsComputational Neuroscience ModelingNon-invasive Brain Interventions

Probable LBNL Areas

BSACSAEESAESAETALDPSA· Combination Therapies· Organoid Models

Focus Areas

Example Priorities:

Design, assembly, and integration of clinical-ready prototype systems with a credible pathway toward human application.
The delivered prototype must consist of an integrated intervention system combining therapeutics, biologics, devices, physical modalities, behavioral interventions, or combination approaches with existing human safety data or established regulatory pathways.
Demonstrate and validate this integrated prototype system in clinical populations or translationally relevant animal models to quantitatively confirm the selective induction of adaptive neuroplasticity.
Metrics are calibrated to de-risk immediate clinical viability... ensure the intervention can overcome systemic clearance mechanisms (e.g., the blood-brain barrier) without causing off-target toxicity.

Specific Technical Skills:

Systems IntegrationTranslational Animal ModelsClinical Trial DesignRegulatory Affairs (IRB/FDA)Human Subjects ResearchTherapeutic Delivery SystemsQuantitative Biomarkers (fMRI, PET)BiostatisticsCombination TherapiesDevice Engineering

Potential PIs for this Area:

Name	Score	Organization
Michael Crommie	0.72	ESA \| MSD \| Material Physics · Device Engineering
Cynthia Regnier	0.72	ETA \| Building Tech. & Urban Sys. \| Whole Building Sys Dept · Systems Integration
Mengjie Yu	0.72	ESA \| MSD \| Material Physics · Device Engineering
Han Lee	0.71	PSA \| Engineering \| Electronic Engineering · Systems Integration
Gerard Marriott	0.71	BSA \| Molecular Biophysics & Integrated Bioimaging \| Cellular & Tissue Image · Therapeutic Delivery Systems
Gregory Lemieux	0.70	EESA \| CESD \| Earth System Sciences · Human Subjects Research
Steven Hofmeyr	0.70	CSA \| AMCR \| Computer Science · Biostatistics
Jennifer Rosenbluth	0.70	· Combination Therapies
Kevin Fan	0.69	LD \| LD \| Strategic Partnerships · Quantitative Biomarkers (fMRI, PET)
Alex Newkirk	0.69	ETA \| Building Tech. & Urban Sys. \| Bldg & Industrial App Dpt · Regulatory Affairs (IRB/FDA)

Example Priorities:

High-risk, high-payoff design and laboratory-scale synthesis of novel, proof-of-concept prototype platforms that establish fundamentally new approaches for selectively inducing adaptive neuroplasticity.
The delivered prototype may include novel biologics, engineered cellular systems, biomaterials, synthetic biology, precision neuromodulation, behavioral paradigms, or other enabling technologies.
Performers may construct and evaluate these prototypes in vitro or in preclinical animal models, but should establish proof-of-concept.
Metrics prioritize the rigorous validation of novel targeting physics or de novo molecular gating.

Specific Technical Skills:

Synthetic BiologyMolecular EngineeringBiomaterials ScienceCellular EngineeringPreclinical In Vivo ModelsIn Vitro AssaysOrganoid ModelsGene-Editing TechnologiesPrecision NeuromodulationComputational Neuroscience

Potential PIs for this Area:

Name	Score	Organization
John Dueber	0.74	BSA \| Biological Systems & Engineering \| Biodesign Dept · Synthetic Biology
Jay Keasling	0.74	BSA \| Biological Systems & Engineering \| Biodesign Dept · Synthetic Biology
David Carruthers	0.74	BSA \| Biological Systems & Engineering \| Biodesign Dept · Cellular Engineering
Michal Kosicki	0.73	BSA \| DOE Joint Genome Institute \| JGI Technology Dept · Gene-Editing Technologies
Christoph Kirst	0.73	CSA \| SciData \| Data & Computational Science · Computational Neuroscience
Grace Lau	0.73	ETA \| ESDR \| Energy Storage & Dist Dpt · Biomaterials Science
Paul Ashby	0.73	ESA \| MF \| MF Image and Manipulation · Molecular Engineering
Jennifer Rosenbluth	0.72	· Organoid Models
Kevin Fan	0.70	LD \| LD \| Strategic Partnerships · Precision Neuromodulation
Jamie Inman	0.70	BSA \| Biological Systems & Engineering \| Department of BioEngineering and BioMedical Sciences · Preclinical In Vivo Models

Example Priorities:

The central hypothesis of this effort is that spatially and temporally confined induction of neuroplasticity will substantially improve the therapeutic index of neuroplastic interventions.
Determine if adaptive neuroplasticity can be induced with sufficient selectivity to preferentially modify intended neural substrates while limiting off-target remodeling.
Intervention Selectivity – The proposed intervention preferentially influences the intended neural substrate, where appropriate to the proposed mechanism.
Biological Target Engagement – The intended biological mechanism is selectively engaged within the target relative to appropriate nontarget controls.
Selective Neuroplasticity – The intervention produces greater adaptive neuroplasticity within the intended neural target region as compared to a positive control intervention.

Specific Technical Skills:

NeuroscienceElectrophysiologyMolecular BiologyFunctional ImagingComparative AnalysisAssay DevelopmentQuantitative AnalysisExperimental DesignControl GroupsStatistical Powering

Potential PIs for this Area:

Name	Score	Organization
Karthik Shekhar	0.72	BSA \| Biological Systems & Engineering \| Biodesign Dept · Neuroscience
Kevin Fan	0.72	LD \| LD \| Strategic Partnerships · Functional Imaging
Morgan Price	0.71	BSA \| Env. Genomics & Sys. Biology \| Comparative and Funct Genomics · Comparative Analysis
Jason Lowe-Power	0.71	CSA \| SciData \| Data Science Applications · Statistical Powering
Drew Paine	0.71	CSA \| SciData \| Data Science Applications · Experimental Design
Marion Russell	0.70	ETA \| Energy Analysis \| Systems & Energy Tech Analysis · Quantitative Analysis
Benjamin Cole	0.70	BSA \| DOE Joint Genome Institute \| JGI Science Dept · Molecular Biology
Michael Mahoney	0.70	CSA \| SciData \| Data Science Research · Control Groups
Adam Deutschbauer	0.70	BSA \| Env. Genomics & Sys. Biology \| Comparative and Funct Genomics · Assay Development
Ehud Isacoff	0.69	BSA \| Molecular Biophysics & Integrated Bioimaging \| Cellular & Tissue Image · Electrophysiology

Potential LBNL PIs (Overall)

Note on PI Matching: These suggestions are generated through an AI-driven semantic analysis of LBNL staff profiles.

Name	Score	Organization
John Dueber	0.77	BSA \| Biological Systems & Engineering \| Biodesign Dept · Synthetic Biology
Christoph Kirst	0.75	CSA \| SciData \| Data & Computational Science · Computational Neuroscience Modeling
Jay Keasling	0.75	BSA \| Biological Systems & Engineering \| Biodesign Dept · Synthetic Biology
Gerard Marriott	0.75	BSA \| Molecular Biophysics & Integrated Bioimaging \| Cellular & Tissue Image · Cellular Engineering
Behzad Rad	0.75	ESA \| MF \| MF Biological Facility · Molecular Engineering
Ting Xu	0.74	ESA \| MSD \| Material Physics · Biomaterial-Based Delivery
Banumathi Sankaran	0.74	BSA \| Molecular Biophysics & Integrated Bioimaging \| Structural Biology Dept · Biological Target Engagement
Karthik Shekhar	0.74	BSA \| Biological Systems & Engineering \| Biodesign Dept · Neural Circuit Targeting
Kevin Fan	0.73	LD \| LD \| Strategic Partnerships · Quantitative Neuroscience Assays
Ehud Isacoff	0.72	BSA \| Molecular Biophysics & Integrated Bioimaging \| Cellular & Tissue Image · Electrophysiological Analysis

Fundamental Research Exemption (FRE)

As of the date of publication of this opportunity, the Government expects that program goals as described herein may be met by proposers intending to perform fundamental research and does not anticipate applying publication restrictions on research results (i.e., papers, journal articles, etc.) to individual awards for fundamental research that may result from this opportunity.