This Request for Applications (RFA) seeks proposals to establish and develop collaborative networks that bring together patient organizations and researchers engaged in single-cell biology. The overarching goal is to support interdisciplinary teams as they characterize the cellular mechanisms underlying rare inflammatory diseases, including possible identification of biomarkers and elucidation of disease pathways that will clarify disease stratification or identify therapeutic opportunities. Patient organizations are expected to be active collaborators on this research opportunity and full partners in the development of the grant application to directly inform research questions that will have the greatest impact on rare disease patients, and to engage in study design, patient engagement, and research dissemination. Applications for this funding opportunity should be focused on single-cell analysis of rare pediatric diseases with a specific interest in clarifying those with a distinct or primary inflammatory pathology. This opportunity builds on our current efforts to support single-cell technology and community development in our work with the Human Cell Atlas (HCA) and related research communities, alongside our learnings from our Rare As One Network of patient-led rare disease organizations as they build and strengthen their organizational and scientific capacities to advance progress against rare disease. This new network will build on and integrate with our Pediatrics and Inflammation single-cell research networks, as well as our Rare As One Network. To learn more, read our Medium posts on rare disease, inflammation, and pediatrics.
Rare diseases can be particularly difficult to study due in part to the high degree of heterogeneity of the diseases, often seen within small and dispersed patient populations. Rare diseases classified by associated genetic variation in distinct patients may impact a complex suite of tissues, and manifest in various systems and organs differently. The underlying cellular mechanisms can be elucidated with the help of single-cell technologies which offer a high resolution lens to understand rare inflammatory diseases. The technologies are thus poised to rapidly discover biomarkers, clarify relationships between similar diseases for further study, provide insights into disease pathogenesis, and stratify patient populations towards clearer diagnoses and more successful treatments. The goal of this RFA is to foster collaborations that will provide such insights and simultaneously provide near-term value to the patient community, as well as highlight important future directions for fundamental research into these diseases. The collaborative nature of the work will result in the development and dissemination of shared knowledge.
This funding opportunity aims to create and foster collaborations where biomedical researchers and patient-led rare disease organizations are true partners. Prioritization of patient needs is accelerated by partnerships between leading scientific researchers and patients throughout the research process, such that they can co-develop research agendas and coordinate sharing resources and insights. We hope that this approach will facilitate research with greater impact, and produce findings that are more translatable and reflective of patient needs.
Priority will be given to applications that address health disparities or focus on rare diseases that predominantly affect underrepresented populations, particularly ancestries that are underrepresented in biomedical research.
Additionally, we hope the network of teams funded by this RFA will generate and disseminate solutions that enable the ethical collection and sharing of rare disease patient biospecimens, taking into consideration the challenges associated with the vulnerable status of pediatric and rare disease donors. These include but are not limited to engagement with communities and families/patients, ancestral diversity, and storing tissue for subsequent analysis. These projects may promote collaboration with other related CZI-funded patient and research networks and projects such as Inflammation, Pediatrics, Ancestry Networks, Rare As One, the Neurodegeneration Challenge Network, Essential Open Source Software for Science, and others.
Specific project focus areas may include, but are not limited to:
- Understanding the pathophysiology of rare inflammatory pediatric diseases at the cellular and molecular levels
- Application of single-cell methods to identify expression profiles, pathways, cell-types, or states involved in disease diagnosis, progression, or to clarify heterogeneity among individuals impacted by a single, or related, rare disease
- Developing new experimental and analytical tools to dissect rare inflammatory diseases at the single-cell level
- Identification of predictive and diagnostic biomarkers to understand disease progression and which biological and inflammatory features drive rare disease severity
- Improving patient stratification/classification through application of single-cell approaches
- Expanding disease modeling for rare disease translational research and connecting understudied genes to model systems, including clarifying how variants of unknown significance manifest in differing cellular pathology
Collaboration is a central feature of this RFA and grant program. Applications will each have two lead Principal Investigators (PIs): one representing the research team and the other representing the patient organization. Teams should be made up of a minimum of two investigators with a maximum of five investigators, including the patient organization leader. Applications should be co-written by the researchers and the patient organization representative. Applications will be accepted from newly formed collaborative teams who have not previously worked together or established researcher-patient organization collaborative teams who are proposing new research directions. We will prioritize teams that are taking a fresh, innovative approach to tackling these challenging diseases.
The criteria below for team composition are intended to allow for flexibility in team composition, while ensuring that there is strong co-ownership of the collaboration between the research team and patient-advocate partners. If applicants have a question about their team’s composition and eligibility, please contact email@example.com.
To allow close collaboration and coordination of research efforts, this RFA is focused on small group collaborations. Teams should be made up of a minimum of two PIs to a maximum of five PIs. All PIs are expected to actively contribute to the project and engage in program and network level activities, such as investigator meetings and workshops where relevant. Below we describe the roles of the PIs.
- Coordinating research PI / lead-research PI: Teams should designate a coordinating PI, the scientific lead of the research project, who coordinates the research team. The lead-research PI will also be the Coordinating PI of the grant to submit the application on behalf of the collaborating team. The Coordinating PI will act as the administrative contact between CZI and all other co-PIs on the grant. The Coordinating PI must submit the application on behalf of all PIs (including the Lead Patient Organization PI, see below) and ensure that the collaborative team has the necessary skills to deliver on the aims of the project. The Coordinating PI must be affiliated with the academic/research institution submitting the application, and grant funds will be awarded to that institution, which will take responsibility for distributing funds to all other research institutions (patient funds will be awarded directly to the patient organization). Note that institutions outside the U.S. may not subcontract to U.S. institutions, so please be mindful when selecting the Coordinating PI/institution.
- Lead Patient Organization PI: Who will represent the patient organization. The research team should coordinate with one patient-led rare disease organization. If the project requires collaboration with more than one patient-led rare disease organization, please reach out to firstname.lastname@example.org to discuss.
- Up to three additional co-PIs:
- Teams may designate up to three additional research co-PIs from one or more research institutions. Co-PIs may be from the same or different research institutions as the Coordinating PI. The strongest applications will incorporate experience with both computational and experimental single-cell biology. Teams may also include additional collaborators and contractors, but only three individuals can be listed as research co-PIs.
- Each team must include at least one clinician with expertise relevant to the application and experience working with patients in this disease area. It is allowable for the clinician to either be located at a research institution or be designated as the Lead Patient Organization PI.
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, LGBTQ individuals, and organizations representing disease areas that disproportionately impact underrepresented or underserved communities.
- Researchers and patient organizations from the Global South and low-to-middle income countries, in particular those with populations that have historically been underrepresented in biomedical research, are strongly encouraged to apply and to be included as members of international collaborative networks. International collaborations between investigators and rare disease organizations in the Global North and South 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
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.
- In addition to providing funding, CZI acts as a scientific partner to grantees to help build open and accessible tools and datasets that serve as references for healthy and disease states. Investigators will have the opportunity to learn from, collaborate, 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 PIs listed on the application are expected to participate in project meetings, reports, and other events. Networks should be genuine collaborative projects with responsibility and participation distributed across participating research groups and organizations. Members of funded labs with key roles in the project—such as students, postdocs, and staff—will also participate in scientific meetings, hackathons, and other activities, and relevant members of patient organizations will also be included in such events. The Rare As One team will also expand access to some of its relevant training and support program offerings to both the researchers and organizations that are listed as co-PIs on this grant, and will develop targeted trainings to support this specific collaborative opportunity.
- CZI’s mission is at the interface of technology and science. Working in collaboration with, and guided by, other grantees in the Network 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 and collaboration, 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.
- CZI believes that the people most affected by problems should be centered in developing solutions to those problems. We work with patient communities to ensure they are heard and recognize patients, patient communities, and organizations as key partners in research.