The Chan Zuckerberg Initiative invites applications from collaborative teams bringing together patient-led rare disease organizations and research teams for 4-year research projects aimed at advancing our understanding of the fundamental science of rare diseases. The Patient-Partnered Collaborations for Single-Cell Analysis of Rare Inflammatory Pediatric Disease RFA aims to support the application of single-cell biology methods to rare inflammatory pediatric diseases that will clarify cellular mechanisms of disease, understand disease heterogeneity, and improve biomarker identification or diagnostics.

Awards are $2,000,000 USD total costs for four years for each project (distributed amongst research institutions and a patient organization). The award period for each RFA is an initial two years of funding, followed by an additional two years, pending evaluation.

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.

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.

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

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 sciencegrants(ELIMINAR)@chanzuckerberg.com 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.

For further information on Elegibility criteria, please refer to the Call Text attached down below.

All applications must be completed and submitted through CZI's online grants management portal at https://apply.chanzuckerberg.com. It is recommended that applicants familiarize themselves with this portal well in advance of the application deadline.

In case of interest in this call, please contact leonor.norton(ELIMINAR)@sjd.es