The Human Cell Atlas (HCA) is a global effort to create a reference map of all cell types in the healthy human body in order to generate a fundamental reference for biomedical research and improve our understanding of health and disease. With advances in single-cell biology technology and growing interest from the international community, this scientific grassroots project has progressed from conceivable to feasible. Progress over the past several years has resulted in remarkable advancement toward first drafts of many adult organs and tissues. However, similar reference data for pediatric tissues is less commonly represented in emerging tissue atlases. Yet this data is critically important for clarifying cellular maturation through childhood while building a foundation for understanding disease progression and therapeutic strategies in children.
This Request for Applications (RFA) welcomes proposals that will make significant contributions toward single-cell reference data for the community of patients, clinicians, and researchers engaged in pediatric research. This opportunity is intended to support active collaborative teams of researchers that have access to established resources and protocols that are ready to be extended and scaled. The opportunity is also intended to support new collaborative teams that will benefit from the experience of existing teams while bringing complementary and differentiated perspectives and resources. The opportunity aims to support a variety of collaborative teams that will all make contributions to the larger community via regular engagement and sharing of learnings, data, samples, and other resources.
Teams should consist of at least three principal investigators (PIs), including at least one computational biologist or data scientist, one pediatrician actively engaged in clinical care, and at least one expert in single-cell biology. Community-engaged researchers should be involved in the collaboration and can come from domains including medicine, public health, fundamental research, or others that will ensure that the research is attuned to the needs of and connected with the participating communities providing pediatric tissue samples. The engagement researchers are incorporated into this opportunity to help provide, promote, and build culturally competent connections with the research participants and members of their community in such a manner that they are empowered to participate in Pediatric Networks research and also benefit from potential findings. This RFA is intended to support established teams as well as new collaborations. It is anticipated that successful applications will include teams that vary in size from small (three to four PIs on the team) to midsized (five to 10 PIs on the team) working together to make progress toward reference maps of healthy pediatric tissues. The goal of this team structure is to:
- Support continued progress among existing teams that have begun to develop resources, generate data, or progress toward single-cell references of pediatric tissues;
- Provide a flexible opportunity that encourages coordination across multiple existing efforts that would benefit from central support to help amplify the impact or increase the scale of current work;
- Provide a mechanism for new teams to establish a collaborative network and develop the necessary capacity to inclusively engage pediatric populations from a diversity of ancestries and lived experience; and
- Generate data to contribute to the first draft of the HCA while helping teams build capacity for future collaborations to expand the initial effort, attract new collaborators, or apply for future funding opportunities.
Many diverse collaborations have been initiated in the HCA, while many additional groups are looking for ways to contribute and engage further. This RFA seeks to support the continued growth of nascent projects and to incubate new networks. We welcome applications from teams of researchers that currently collaborate and have access to established resources and protocols that are ready to be extended and scaled. However, we also intend for this opportunity to support new collaborative teams that will benefit from the experience of existing teams while bringing complementary and differentiated perspectives and resources. The Pediatric Networks should collectively generate new tools, open source analysis methods, and data from a diversity of donors and organs that provide valuable contributions to the HCA community. Applications should focus on healthy human tissues that will contribute to a reference atlas. Community resources arising from the Pediatric Networks teams must be accessible for rapid and open sharing via repositories such as Protocols.io, Addgene, GitHub, and bioRxiv. Raw sequencing data should be submitted in an archive that maximizes accessibility while adhering to key ethical considerations, including attention to privacy and consent protections specific to pediatric populations.
CZI Pediatric Networks grants have the following overarching scientific goals:
- Generate and share data that will contribute to and establish references for organs and tissues during age windows that will clarify childhood development and maximize utility for understanding pediatric disease;
- Represent diverse ancestries in data collected, with the goal of generating references that will promote understanding of disease in populations and communities with increased incidence of childhood disease;
- Build international collaborations that promote coordinated and cohesive progress and contribute to the Human Cell Atlas;
- Identify and address shared computational or infrastructural bottlenecks, to ensure that data generated as a part of this reference can be analyzed, incorporated, and shared as a part of a global reference;
- Collect and share biospecimens, including generating and disseminating solutions for challenges associated with ancestral diversity and vulnerable status of young donors, engagement with communities and families/patients, and storing tissue for subsequent single-cell analysis; and
- Promote collaboration with other funded tissue networks and projects that are actively involved in the HCA as well as other CZI efforts, such as Rare As One, Inflammation, the Neurodegeneration Challenge Network , Essential Open Source Software, and others.
Specific examples may include, but are not limited to:
- Focused atlases or data generation on single organs, tissues, or multiple organs from single donors;
- Opportunities to develop and share tissue resources that will support standards, protocols, and tissue access to pediatrics researchers and clinicians; and
- Computationally focused networks that will address common challenges faced with the assembly, interpretation, and use of pediatric reference data.
Collaboration and Open Science
All projects will be evaluated based on their potential for scientific output (productivity), tool and resource dissemination (reach), inclusion of representative donors and communities, and collaboration among the team. We are looking for investigators and groups who will enthusiastically contribute to and benefit from a collaborative, dynamic, and interdisciplinary approach. For examples of evidence of productivity, reach, and collaboration, please see the CZI statement of values.
- CZI will work with investigators to help build the HCA. Investigators in the Pediatric Networks will have the opportunity to learn from, collaborate with, and interact with the community of investigators and groups across all Networks, as well as with CZI computational biologists and software engineers.
- CZI supports collaboration. All Principal Investigators listed on the application are expected to participate in meetings, reports, and other events. Networks should be genuine collaborative projects with responsibility and participation distributed across participating research groups. Members of Pediatric Networks labs with key roles in the project (students, postdocs, and staff) will also participate in scientific meetings, hackathons, and other activities.
- CZI’s mission is at the interface of technology and science. Working in collaboration with and guided by other Pediatric Networks grantees and the wider HCA community, we aim to develop technology-based tools and approaches to support and accelerate the scope and impact of tissue atlases and the HCA community.
- 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.