The CZI Neurodegeneration Challenge Network (NDCN) was launched in 2018 as a new type of collaborative research network that brings together biologists, computational scientists, engineers, and physicians from across broad research areas who are motivated by collaboration and open science to tackle unsolved challenges in neurodegenerative disease. Collaboration has been at the core of the vision for the Challenge Network approach and in developing the NDCN program strategy, we have sought to develop funding mechanisms that motivate and support novel collaborative approaches that will lead to bold, innovative, risk-taking science.
The Collaborative Pairs Pilot Project Awards were developed as a funding mechanism to catalyze new collaborations and scientific partnerships and springboard early-stage projects that are bold, creative and “out-of-the-box.” We recognize that great collaborations can take many forms — from teams of two to large consortia and everything in between. The Collaborative Pairs mechanism focuses specifically on pairs of investigators. While scientific creativity is often represented as emanating from a singular lone genius, science works best when it is a collaborative effort, and it’s often creative duos and partnerships that fuel the engines of innovation.
In 2019, we launched the first cycle of Collaborative Pairs Project Awards, funding 30 teams to explore innovative approaches addressing cross-cutting questions related to neurodegenerative disease biology. The application process was designed to encourage new teams and new ideas — no preliminary data, previous work together, or prior experience in neurodegeneration research was required to apply. We looked for talent, expertise, and great ideas. The first cohort of Collaborative Pairs working on 30 pilot projects included cell biologists, RNA biologists, neuroscientists, immunologists, cancer researchers, computer scientists, and even a plant biologist. Many of these investigators were new to neurodegeneration research. Sixteen of these projects have now moved forward to the second, four-year acceleration phase, where they are breaking new ground in unraveling the underlying mechanisms of neurodegenerative diseases. Learn more about the vision for the Collaborative Pairs Pilot Project Awards through this Medium post and more information about the teams who were funded through Cycle 1 on our website.
Building on the successes of the Challenge Network and the first cycle of Collaborative Pairs, we are now pleased to invite applications for a new Request for Applications (RFA) that supports Cycle 2 of the Collaborative Pairs Pilot Project Awards. For this new cycle of the Collaborative Pairs, we are excited to broaden the scope of our network to also support investigations into areas of fundamental neuroscience beyond neurodegenerative disease, in particular in areas where there is potential for complementarity or synergy with our existing work in the Neurodegeneration Challenge Network and/or other CZ Science program areas. This expanded RFA scope includes basic investigations into the cellular, molecular and circuit mechanisms of memory and cognition and the neuroscience of sleep.
We are excited about this next chapter for the Challenge Network and neuroscience at CZI. With the view that a better understanding of the fundamental mechanisms of brain function in the healthy brain will also be critical for contextualizing the types of processes that go awry in neurodegenerative disease, we believe that this expanded neuroscience scope will allow us to continue to bring together innovative, cutting-edge scientists from across a range of disciplines to develop new ideas and approaches for tackling the many unsolved questions in neurodegenerative disease. And, likewise, we see tremendous opportunity for extending the Challenge Network approach and collaborative models to other areas of neuroscience.
The Collaborative Pairs Pilot Project Awards (Cycle 2):
The Collaborative Pairs program will be a two-phase process:
Phase 1 of the Collaborative Pairs grants RFA will provide seed funds for new interdisciplinary collaborations involving a pair of investigators and their labs to pursue a pilot project towards addressing a critical gap in the field (see section on scope below). Each pair is required to include at least one early or mid-career researcher (less than 10 years in an independent academic PI role). Collaborative Pairs projects will be funded for 18 months ($200,00 total costs/collaboration) for a pilot phase where teams will generate tools and data and further develop their project proposal and team, with the main goal being the development of a project plan for Phase 2. Funded teams will benefit from the support, mentoring and collaborative interactions of the Challenge Network, as well as interactions with the broader CZ Science programs and grantee network.
The purpose of the phase 1 Pilot Project Award is to give the collaborating teams the freedom to explore new, out-of-the-box, potentially transformative ideas. We are looking for teams and proposals that are addressing a critical problem and doing so in a bold, innovative way.
In Phase 2, Collaborative Pairs teams that received pilot project funding and have successfully progressed their project will be eligible to apply for an acceleration grant award of $400,000 total costs/year/pair for four years ($1.6 million total) to build on the work done in the pilot phase, for a total of $1.8 million over five-and-a-half years for the entirety of the project (Phase 1 and Phase 2).
The Collaborative Pairs Pilot Project Awards RFA is focused on foundational and mechanistic basic science investigations. Building on and expanding from the successful foundations of the Neurodegeneration Challenge Network, applications may address fundamental questions related to the cellular, molecular or circuit mechanisms of neurodegenerative disease or areas of fundamental neuroscience beyond neurodegenerative disease. This expanded RFA scope includes basic investigations into the cellular, molecular and circuit mechanisms of memory and cognition and the neuroscience of sleep. We particularly encourage proposals where there is potential for complementarity or synergy with our existing work in the Neurodegeneration Challenge Network and/or other CZI program areas.
This is explicitly not a translational or clinical development RFA. Nonetheless, successful projects should be grounded in human biology, disease pathology, or fundamental principles of nervous system function such that the outputs of these efforts will ultimately provide new avenues and rigorous foundations for future translational and clinical development work.
We encourage applications both from investigators who are tackling underexplored topics, as well as those addressing more well-developed areas of science where there remain significant gaps in understanding. Pairings should take an innovative, interdisciplinary approach to address these knowledge gaps in ways that leverage each researcher’s unique, complementary area of expertise. For example, we’re looking for collaborative research projects that bring together experimentalists with computational biologists or technology developers, or collaborations that bridge multiple disciplines like immunology, cell biology, neurophysiology, genetics, biochemistry, stem cell biology, and bioengineering.
Examples of potential areas that would be within scope for this program include, but are not limited to:
- Testing causal hypotheses for the role of circuit, cellular and molecular mechanisms in neurodegenerative disease pathogenesis across the lifespan.
- Defining the contribution of non-neuronal influences on neurodegeneration or healthy brain function, including potential contributions of the innate and adaptive immune systems, brain vasculature, and the gut and microbiome to nervous system function.
- Cellular- and systems-level approaches to studying neural plasticity, aging, and resilience in the context of neurodegenerative disease or healthy aging.
- Investigating the causal contribution of well-defined cell types or circuits in cognitive processes or sleep-wake cycles.
- Investigating interactions between central nervous system (CNS) sleep circuitry and fundamental cellular processes in peripheral organs and tissues of the body.
- Partnerships between computational and experimental biologists that advance the development and validation of data analysis and data integration approaches, including but not limited to machine learning and artificial intelligence applications.
Examples of potential areas that would be out of scope for this program include:
- Clinical research investigations involving human research participants and patients, including human neuroimaging studies.
- Translational therapeutic or drug development research programs.
- Fundamental investigations in nervous system disease or injury contexts outside of neurodegeneration, such as neurodevelopmental diseases or psychiatric disease.
Building Tools to Support the Neurodegeneration Research Community
As part of the collective work of the Challenge Network, CZI asks investigators to contribute to the development, validation, and dissemination of robust, reliable, and scalable experimental and analytical tools for the broader research community. We particularly encourage applications that seek to develop, validate and disseminate new technologies and methodological approaches and of pairings of experimentalists and technology developers.
Examples of the types of tools and resources that Challenge Network grantees have contributed towards include:
- Well-validated and reliable platforms for human cell biology, which might be based on tissue samples, iPSCs, organoids, or other advanced tissue biology systems.
- Scalable tools for cellular analysis, including genomic, proteomic, and imaging methods optimized for human cells and relevance to neurodegeneration (for instance, targeted probes and label-free methods for cellular imaging of neurons and non-neuronal cells; robust affinity reagents for proteomics; genome editing and single-cell genomic approaches).
- New tools to improve the specificity, resolution, and scale of cell-type and circuit targeting for phenotyping, monitoring, or manipulation.
- Well-validated, robust, shared animal models that more accurately model human disease biology.
- Unique human tissue resources and associated protocols for their handling and best use.
- Rigorous benchmark datasets for the field, for instance, well-validated longitudinal studies of disease progression that will inform more mechanistic approaches.
- Development and application of computational and machine learning approaches and tools to address neurodegeneration biology, which might include genomics, proteomics, metabolomics, systems biology, imaging, and/or integration of data across experimental models and scales.
Diversity, Equity, & Inclusion
- We believe that the strongest teams incorporate a wide range of voices. Those underrepresented in science and technology are strongly encouraged to apply. This includes but is not limited to women, those with disabilities, underrepresented racial and ethnic groups, LGBTQIA+ individuals, and organizations representing disease areas that disproportionately impact underrepresented or underserved communities.
- Researchers from populations that have historically been underrepresented in biomedical research are strongly encouraged to apply. International collaborations between investigators that leverage regional and technological expertise and strengths are encouraged. It is the expectation that international collaborations will follow guidelines for conducting research in an equitable and mutually beneficial manner.
Collaboration and Open Science
The CZI Neurodegeneration Challenge Network is an approach to address the scientific challenges of neurodegenerative diseases and an experiment in collaborative science. As part of the selection process, we will look for investigators and groups who will enthusiastically contribute to and benefit from a highly collaborative, dynamic, and interdisciplinary approach. For examples of evidence of productivity, reach, and collaboration, please see the CZI statement of values.
- Investigators in the Challenge Network will have the opportunity to learn from, collaborate with, and interact with the community of investigators and groups within the Network, as well as with Chan Zuckerberg Initiative scientists and software engineers. Investigators and members of their labs will participate in regular investigator meetings, meetings for students, postdocs, and staff, as well as mentorship and training opportunities.
- CZI’s mission is at the interface of technology and science. Working in collaboration with, and guided by, Challenge Network investigators, we aim to develop technology-based tools and approaches to support and accelerate the broader field of neurodegeneration.
- Clinical partners in these collaborative projects will play important roles as mentors to help the collective work of the Challenge Network stay closely aligned to the clinical contexts of these disorders and to the needs of patients.
- CZI supports open science values and principles. To accelerate scientific discovery, collaboration, and rapid dissemination, CZI supports a consent, sharing, and publication policy for open and rapid dissemination of research results and a policy for software development that maximizes accessibility, reuse, and shared development.
Criteria we will be looking for in the Collaborative Pair Pilot Phase applications include:
- New collaborations: To be eligible, proposed pairs cannot have received prior joint grant funding. Applicants will be asked to describe the nature of their collaboration and what unique perspective this pairing brings to the proposal.
- Multi-institutional pairings: While collaborations within a single institute are eligible to apply, we are especially encouraging of new collaborations that bridge two distinct institutions. International collaborations are welcome and encouraged.
- Strong partnerships that leverage complementary strengths: We will be looking for collaborations that bring together complementary, balanced skill sets and approaches. We strongly encourage applications from collaborations involving clinicians and physician-scientists, as well as pairs that bring together researchers from different fields, for instance: connecting experimental biologists and computational biologists; pairing technology developers with applied experimentalists; or bridging between multiple disciplines like immunology, cell biology, neuroscience, biochemistry, stem cell biology, and bioengineering.
- Bold, innovative, high-impact proposals: We are seeking proposals that address important, not incremental, problems in a creative way. This mechanism is an opportunity to take well-calculated strategic risks. We expect that some collaborations will succeed, even if the pilot phase experiments fail and are encouraging of this kind of risk-taking science.
- Early- or mid-career investigators: Each pair must include at least one early- or mid-career researcher, someone who has been in an independent academic role for less than 10 years (see eligibility criteria for details).
- New investigators to the field: The scope of this RFA includes broader areas of neuroscience. We continue to encourage applications with proposals that address fundamental challenges related to neurodegenerative diseases but applications are not required to focus on disease or neurodegeneration. There is no requirement to have worked in neurodegeneration research before and we encourage cross-over work from diverse disciplines.
- Diversity: We aspire to create a diverse community in the Challenge Network and strongly encourage applications from women, those underrepresented or marginalized in science, and diverse groups worldwide. See application instructions and eligibility criteria for specific details on eligibility.
- The final determination of awards and numbers will depend on the quality of the applications received at CZI’s sole discretion.