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Discovery Research Grants Request for Applications Cycle 4

Breakthrough Discoveries for thriving with Bipolar Disorder (BD 2)

We invite you to apply for a Breakthrough Discoveries for thriving with Bipolar Disorder (BD2 ) Discovery Research grant. This program supports an innovative and collaborative group of researchers working together to improve our understanding of the biological mechanisms that underlie bipolar disorder. BD2 will fund teams of multidisciplinary scientists to develop targeted and groundbreaking research applications that examine the genetic, molecular, cellular, circuit, and/or behavioral mechanisms of bipolar disorder. BD2 plans to award up to $1.5 million USD per year for three years (up to a total of $4.5 million) to identified teams of three to five scientists, with an intended opportunity for continued funding up to an additional two years based on strong commitment, productivity, and promise.

Background

Bipolar disorder is a highly complex and heterogeneous disorder that is often debilitating. Even though it is prevalent in about 3% of individuals worldwide, little is known about its underlying biology. Current understanding and treatment of bipolar disorder remain far from ensuring that everyone living with it can manage their condition and lead independent, fulfilling lives. BD2 is the first organization focused on funding and advancing research and care for bipolar disorder on a global scale. Our collaborative, open-science approach is intentionally designed to transform and shorten the time it takes for scientific breakthroughs to make a meaningful difference in the lives of the tens of millions of people with bipolar disorder. For too long, there have been limited advances in the study and treatment of bipolar disorder due to a lack of collaboration and funding. It’s time for a new approach. The BD2 Discovery Research program aims to delineate the etiology and biological mechanisms of bipolar disorder, allowing the development of effective interventions. We are making this a reality by funding multidisciplinary teams of scientists and clinicians who generate new hypotheses and drive innovation in the exploration of causal mechanisms of bipolar disorder with an eye toward novel treatments

The Opportunity

Throughout the decades of bipolar disorder research, it has become clear that research strategies must shift drastically to ensure faster and more significant discoveries. Philanthropic support has presented a once-ina-generation opportunity to develop a unique mechanism to bring the most capable and innovative minds together to explore one of the most complex mental disorders. Teams of three to five scientists may apply to receive up to $1.5 million per year for three years, totaling up to $4.5 million per award. Teams must submit a 2-page letter of intent (LOI) outlining the causal mechanistic hypothesis, goals, general aims, scientific strategies, and methodologies they will employ. This LOI must have a scientific scope that is impactful and will significantly contribute to our understanding of the causal mechanisms of bipolar disorder. Selected teams will then be invited to develop a 5-page application that describes the scientific scope, technical strategies, team capabilities, a comprehensive budget, organizational commitments, and other details. Funded teams will be expected to share resources, data, and progress with other teams in the network throughout the funding period. Teams will also have the opportunity to develop new partnerships with other teams within the network and the potential to access additional collaborative grants. We intend to continue funding an additional two years beyond the original three-year grant period for teams exhibiting strong productivity and promise.

PERTINENT DATES

RFA released September 10, 2025

Webinar for applicants October 8, 2025

Letters of Intent (LOIs) due November 21, 2025

Full proposal invitations December 19, 2025

Full proposals due February 20, 2026

Scientific and strategic evaluation March to June 2026

Awardees notified July 2026

Grants awarded August 2026

AI Based Application Success Predictor

✅ 1. Clear Causal Mechanistic Hypothesis

BD² is explicitly mechanism-focused — it funds projects designed to uncover fundamental causal drivers of bipolar disorder at multiple levels (genetic → circuit → behavior). milken.smapply.io

Success predictor:

Propose a strong, biologically grounded hypothesis about how specific mechanisms contribute to bipolar disorder etiology, progression, or symptom expression.

Avoid overly descriptive or purely correlative research — focus instead on causation and mechanism testing.

✅ 2. Multidisciplinary, Collaborative Teams

BD² requires teams of three to five scientists with complementary expertise (e.g., genetics, neuroimaging, computational biology, behavioral neuroscience). milken.smapply.io

Success predictor:

Assemble a team where each member brings a distinct, expert methodology aligned with the project’s causal hypothesis.

Demonstrate how teamwork enhances feasibility and scientific reach beyond what single labs could achieve.

✅ 3. Hypothesis-Driven, Innovative Approaches

Proposals are expected to go beyond incremental extensions of existing research and instead push scientific boundaries. GlobeNewswire

Success predictor:

Design novel experimental strategies — such as cutting-edge genomics, advanced neuroimaging, neuromodulation, or integrative multi-omics — that address gaps in current understanding.

Tie methods directly back to the hypothesis with logic and feasibility.

✅ 4. Robust Experimental Design With Realistic Milestones

BD² applicant materials emphasize specific aims, detailed methods, and timelines that match a 3-year funding window (with possible extension for exceptional productivity). milken.smapply.io

Success predictor:

Provide a stepwise plan with clear milestones, decision points, and contingency strategies.

Include quantitative outcomes and justification of sample sizes, expected effect sizes, and analytical strategies where applicable.

✅ 5. Commitment to Open Science & Data Sharing

BD² operates on an open science model — funded teams are expected to share data, methodologies, and progress within the BD² network and publicly when appropriate. Breakthrough Discoveries (BD²)

Success predictor:

Clearly outline data sharing plans, including repositories, data standards, and timelines for release.

Show readiness to integrate with and contribute to broader BD² collaborative efforts.

✅ 6. Alignment With Program Priorities

BD² RFAs for recent cycles clarify priority research areas that reflect urgent knowledge gaps in bipolar research: GlobeNewswire

Cellular and molecular mechanisms of mood-state switching

Biological responses to environmental or physiological risk factors

Experimental pharmacology probing causality

Neuromodulation programs targeting brain circuits impacting mood regulation

Success predictor:

Choose project aims that fit one or more stated priority areas, and articulate how they address them directly.

✅ 7. Strong Institutional and Team Track Record

Given the very large awards and the scale of collaboration expected, reviewers assess whether the team and host institutions can deliver on ambitious goals.

Success predictor:

Highlight prior work, publications, and experience with large multi-institutional studies or advanced methods.

Show institutional support for resources, data management, and project coordination.

🛠 Typical Application Structure

Based on the BD² RFA process: Breakthrough Discoveries (BD²)

Stage 1 – Letter of Intent (LOI):

2 pages

Hypothesis, general aims, significance, methods overview, team composition

Stage 2 – Full Proposal (invited):

~5 pages

Detailed scientific scope

Technical approach and timeline

Capabilities and roles of team members

Comprehensive budget and justification

Plans for data sharing/network participation

This dual-stage review focuses first on concept and fit and then on feasibility and execution strength.

🧠 Summary: Key Success Predictors

Predictor	Why It Matters
Mechanistic focus	Core mission of BD² is to change biological understanding of bipolar disorder. milken.smapply.io
Multidisciplinary teams	Peer review favors breadth and depth of expertise. milken.smapply.io
Innovative, bold hypotheses	BD² prioritizes scientific breakthrough over incremental studies. GlobeNewswire
Clear experimental plan	Feasibility within large, complex projects is crucial. milken.smapply.io
Data sharing and open science	Expected and valued by BD² for catalyzing field-wide progress. Breakthrough Discoveries (BD²)
Alignment with program priorities	RFAs explicitly list key biological and translational focuses. GlobeNewswire
Strong team & institutional support	Demonstrates capacity to deliver on ambitious scope.

Specialties

Neurosciences

Eligibility Requirements

Applications will only be considered from teams who meet all eligibility criteria below:

Institutional Eligibility

• Each applicant organization must be a non-profit academic or research institution, including domestic and non-U.S. non-profit organizations, domestic and non-U.S. public/private academic universities, or institutions of higher learning (including colleges, universities, medical schools, and other related academic research organizations). Certain governmental agencies with active biomedical research programs may also apply.

• The Lead PI must be affiliated with the institution submitting the application. If the Lead PI’s institution is selected for funding, grant funds will be awarded to that institution, which will take responsibility for distributing funds as subawards to any institutions with which other members of the collaboration are affiliated.

Leadership Eligibility

• Each team must consist of three (3) to five (5) PIs, with one identified as the Lead PI and the rest as co-PIs. Each PI must hold a doctorate (e.g., Ph.D., M.D.) or related research doctorate degree and be affiliated with an institution eligible to hold funds. Each PI is expected to lead a component or subproject within the overall team proposal. PIs can be recruited from existing or previous collaborations, or from new collaborations. PIs from groups that are underrepresented in science are encouraged (see here).

• One PI within each team must be identified as the Lead PI. The Lead PI is responsible for the scientific and technical direction of the proposed research project, contractual and financial obligations, and other organizational assurances and certifications. The Lead PI will submit the application and be the primary point of contact between the research team and the BD2 team during the application and evaluation process, as well as during post-award progress reporting and other matters throughout the entirety of the grant period, if applicable.

• There is no minimum or maximum number of institutions required to be represented within each team. All PIs may be from the same institution, all from different institutions, or a mix thereof, though the interdisciplinarity of the PIs will be strongly considered as a priority.

• Regardless of the size of the team, there must be at least one PI who is considered an early career researcher (ECR). BD2 uses a similar definition as the NIH, defining ECR as a PI who currently holds a fully independent faculty position or equivalent and completed their terminal research degree or post-graduate clinical training in the last 10 calendar years (i.e., 2015 or more recent). For example, a postdoctoral fellow would not be eligible to be a co- or lead PI. The lead PI may be an ECR.

• All PIs must allocate a minimum of 15% of their full time effort (FTE) to the proposed project.

• Regardless of the size of the team, there must be at least two scientific disciplines (i.e., experimental approaches) or areas of expertise represented on the team.

• Individual PIs may be on multiple grant applications but may only serve as the Lead PI on a single application, while being cognizant about the minimum effort required for each grant.

Ineligibility

The following types of applications are not within the scope of this grant opportunity:

• Longitudinal cohort studies, defined as studies tracking human subjects over time;

• Applications that primarily seek to develop new interventional strategies;

• Applications that rely on a single research methodology; or

• Applications that focus on clinical trials, especially recruitment of participants into new or existing trials, or administrative or infrastructure support for new or existing clinical trials.

Sponsor Details

Sponsor Institute/Organizations: Breakthrough Discoveries for thriving with Bipolar Disorder (BD 2)

Sponsor Type: Corporate/Non-Profit

Address: Santa Monica, California, USA, or Washington, D.C., USA.

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