Single-Cell Analysis of Inflammation

Overview

Inflammation is a feature of many diseases and a cross-cutting area of biomedicine. Inflammation mediates the response to chronic and acute tissue injury and infection, driving homeostasis and tissue repair. It is also a driver of fibrosis, cardiovascular disease, inflammatory bowel disease, arthritis, neurodegeneration, adverse events associated with immunotherapies, and many other maladaptive processes. Mapping inflammation in diverse tissues is a path to understanding, diagnosing, and potentially treating many different diseases. 

CZI seeks applications aimed toward identifying unifying principles that underlie tissue homeostasis and inflammation at the single cell level. Our goal is to stimulate collaborations across disciplines that will help define a new field. Successful applications will bring together researchers in different experimental, computational, or medical domains. They will address local cell properties and interactions in inflamed tissues and compare them to the properties and interactions of similar cells in healthy tissues. They will increase our understanding of the cell types that mediate inflammation, and their interactions in space and time. The two-year pilot grant period is intended to develop proof-of-concept for the experimental team and the approach, setting up future programs for detailed mechanistic investigations. 

Structure of Research Teams

This program is aimed toward developing new teams, consisting of two or three principal investigators with different areas of expertise, who can advance interdisciplinary analysis of inflammation. 

Scientific Scope

The long-term goal of this program is to address the mechanisms of inflammation at the cellular level, including its dynamics and resolution, its molecular drivers, and the effects of genetic and environmental risk factors on relevant cellular properties and interactions. 

During this pilot phase, we especially seek proposals that support the development and integration of tools and resources for studying inflammation at the level of local cells and tissues, including volumetric imaging, image-based transcriptomics and proteomics, single-cell transcriptomics, organoids and other tissue models, and computation.

This funding opportunity is explicitly aimed at the cell and tissue level. It is not intended to support clinical trials, drug development, or whole-genome analysis.

Examples of Potential Collaborative Teams and Research Themes 

• Biologist and Biologist
  • Conduct parallel experiments on different tissues (e.g. transcriptomics) to identify common themes in inflammation (cells, signaling, genetics)
  • Combine expertise in two relevant fields (e.g. immunology and neuroscience) to study inflammation at the intersection of those fields
• Technology Developer and Clinician or Biologist
  • Develop, modify, or apply new experimental methods for use in clinical samples
  • Develop, modify, or apply new experimental methods for use on archived human tissues
• Tissue Engineer and Biologist
  • Develop or improve disease-relevant tissue models using human cells, such as organoids or 3D printed tissues
• Computational Scientist and Biologist
  • Develop new analytical methods or visualization tools for studying inflammation-relevant cells, molecules, or tissues
  • Integrate data of different types, for example data from cell culture systems, mouse models, and human clinical samples
• Computational Scientist and Clinician
  • Apply new analytical or machine learning approaches to the cellular analysis of pathology samples
• Clinician and Biologist
  • Curate and analyze high-quality tissue resources such as biopsies from inflammatory diseases and control tissues

We particularly encourage applications from:

• Researchers in disciplines outside of biomedicine who bring new technology, resources, or frameworks to studying inflammation;
• Groups of investigators who have not previously worked together;
• Women, underrepresented minorities, and members of underserved populations; and
• Early career investigators, defined as principal investigators who have been in an independent faculty role for less than six years at the time of application, i.e. starting after November 2013. Independence is typically demonstrated by a full-time faculty appointment, allocated space, a start-up package, and institutional commitment as defined or verified in a letter from a department chair or equivalent.

Desired Outcomes 

Successful outcomes for this RFA could include:

• Development, validation, and dissemination of robust experimental and analytical tools;
• High-quality tissue resources that capture temporal or multi-tissue inflammatory events;

• In vitro models that are experimentally tractable and help translate between human and non-human systems;
• Improved protocols for in situ analysis of cellular identity or interactions;
• Analytical tools that extract features or integrate across diverse data sets;
• Panels of antibodies or other reagents that enable consistent interrogation across tissues or inflammatory conditions;
• Visualization methods that enable access and exploration of data by non-experts; and
• Benchmark datasets for the field that will inform mechanistic approaches, deposited into shared data platforms such as the Human Cell Atlas Data Coordination Platform.

Collaboration and Open Science

To accelerate research in the area of inflammation, CZI seeks investigators who will contribute to a collaborative interdisciplinary network and the advancement of the field.

• Investigators and members of their labs will participate in annual meetings of all funded groups, smaller meetings focused on specific biological or technical issues, and monthly webinars.
• Investigators and CZI staff will work together to identify resources and technology that will support the inflammation field as a whole.

• Investigators will commit to rapid dissemination of all resulting data, protocols, code, reagents, and results prior to publication through resources such as the Human Cell Atlas Data Coordination Platform, protocols.io, GitHub, Addgene, and preprints.

• Applicants must hold a PhD, MD, or equivalent degree.
• Applicants must have an academic appointment and be in an independent faculty position or equivalent at an accredited college, university, medical school, or other research facility. Independence is typically demonstrated by a full-time faculty appointment, a tenure-track position, allocated space, a start-up package, and institutional commitment as defined or verified in a letter from a department chair or equivalent.
• Applications may be submitted by domestic and foreign non-profit organizations; public and private institutions, such as colleges, universities, hospitals, laboratories, units of state and local government; and eligible agencies of the federal government.
• Collaborations should include two or three principal investigators (PIs). 
• Collaborations should be interdisciplinary (some examples are given above).
• Each PI may only participate in one application.
• Principal Investigators on one application may work at the same or at different institutions. 
• Each application should designate one PI as the Coordinating Principal Investigator (Coordinating PI). The Coordinating PI will act as the administrative contact between CZI and all PIs on the grant. The Coordinating PI must submit the application on behalf of all PIs. 
• The Coordinating PI must be affiliated with the institution submitting the application, and grant funds will be awarded to that institution, which will take responsibility for distributing funds to any other institutions. Note that foreign institutions may not subcontract to US institutions, so please be mindful when selecting the Coordinating PI/institution. 
• All grants will be made in compliance with the US Treasury Department’s Office of Foreign Asset Control (OFAC) program. For additional information regarding OFAC sanctions, please refer to the US Treasury Department’s resources.
• Facebook employees, including employees of any subsidiary Facebook entities, are not permitted to apply for this grant.
• CZI reserves the sole right to decide if an applicant and applicant organization meet the eligibility requirements.

For questions about eligibility or the application process, please contact us in advance of the proposal deadline at sciencegrants@chanzuckerberg.com. Deadline extensions will not be granted. 

The Chan Zuckerberg Initiative uses SurveyMonkey Apply (SMApply) as its grants management portal. All applications must be submitted through this portal (https://apply.chanzuckerberg.com). SMApply is configured to work best using the Google Chrome browser. It is recommended that you familiarize yourself with this portal well in advance of any deadlines. Deadline extensions will not be granted.

The application consists of the following sections (called tasks in the grants portal): Applicant Details Part I, Applicant Details Part 2, Organizational Details, Project Details, Project Proposal, Biosketches for all participating PIs, Budget, and Letters of Commitment.

• Applicant Details Part 1: Complete all fields in this task; all fields are required. The information entered should be for the Coordinating Principal Investigator (Coordinating PI), who will be the person submitting the application on behalf of the collaborative team. The Coordinating PI will take responsibility for managing the group collaboration and be the administrative point of contact for CZI and any partners. The Coordinating PI must be affiliated with the institution submitting the application, and grant funds will be awarded to that institution, which will take responsibility for distributing funds to the institutions of the other members of the collaboration. Information about the co-Principal Investigator(s) on the proposal should be entered where requested in the Project Details part of the application.
  • Name and Email: auto filled; to edit your name or email, please do so in your account information by clicking your name in the upper right corner and clicking My Account in the dropdown menu.
  • Organization, Title/Position, Department (or equivalent), Degrees, Early Career status (faculty position 0-6 years).
    • In the context of this RFA, we are defining early career investigator as someone who has been in their faculty role for zero to six years at the time of application, i.e. have started their first independent position between November 2013 and November 2019.
• Applicant Details Part 2: Complete all required fields in this task. The information entered should be for the Coordinating PI who will be the person submitting the application on behalf of the collaborative team. Please note demographic information will not be used as a basis for review.
  • ORCID iD (required): Enter in format XXXX-XXXX-XXXX-XXXX. ORCID iDs are unique, digital identifiers that distinguish individual investigators and unambiguously connect their contributions to science over time and across changes of name, location, and institutional affiliation. ORCID iDs will be used to streamline reporting in our applications and grant reports to reduce the burden on grantees. For more information, please visit https://orcid.org/register. (Please contact us at sciencegrants@chanzuckerberg.com if you wish to opt out).
  • Highest degree (required) and year granted (optional).
  • Additional degrees and year granted (up to three) (optional).
• Gender (optional).
• Race/Ethnicity (optional).
• Short narrative biography of the applicant (maximum of 100 words) (required).

• Organization Details for Coordinating PI: Complete all fields in this task; all fields are required. The information entered should be for the organization of the Coordinating PI who will be the person submitting the application on behalf of the collaborative team. The Coordinating PI must be affiliated with the organization listed, and grant funds will be awarded to this organization, which will take responsibility for distributing funds to the institutions of the other members of the collaboration:
  • Organization:
    • Name: Auto filled from Applicant Details.
    • Address, City, State/Province, and Country.
    • Type of organization (drop down menu: academic/non-profit, industry/company, government, other).
    • Tax ID: Enter your organization’s Employer Identification Number (EIN), as assigned by the Internal Revenue Service in the 9-digit format (XX-XXXXXXX; 10 characters total). Foreign organizations or others who do not have an EIN should enter 44-4444444.
  • Organizational/Administrative Contact: List the name and contact information for the administrative contact to discuss additional information needed, if selected for award.
    • First name, Last name, Title/Position, Email.
  • Signing Official: List the name and contact information for the person authorized to sign on behalf of your organization.
    • First name, Last name, Title/Position, Email.
  • Press Contact / Public Relations Official: List the name and contact information for the person to discuss press releases and media.
    • First name, Last name, Email.
  • Institutional Approval Form: Upload as a single PDF. This form should be printed, reviewed, and signed by a person authorized to sign on behalf of your organization, agreeing to the stated institutional and investigator requirements and commitments on data, resource sharing and publication policies, as well as endorsing/verifying your application materials. In the event of an award, all funds will be awarded to the applicant institution as the prime institution and the applicant institution will be responsible for ensuring compliance of all of the terms, including compliance of all partners/subcontract institutions. While CZI does not require sign-off by all of your partner institutions, please refer to what your institution requires. This field is not designed to support encrypted documents or digital signatures; please sign, scan, and upload this form as a PDF. 

• Project Details: Complete all fields in this task; all fields are required.
  • Project Title: Auto filled; limited to 75 characters, including spaces. If you need to edit your project title, navigate to your application summary page, click on the three dots to the right of the application title (next to the Preview link) and select Rename from the dropdown menu.
  • Project Purpose: Summarize your research project; limited to one sentence; maximum of 255 characters, including spaces.
  • Abstract/Project Summary: Describe your collaborative project; limited to 250 words.
  • Amount Requested: $175,000 maximum total costs per Principal Investigator, including no more than 15% indirect costs; therefore, $350,000 maximum for two PIs and $525,000 maximum for three PIs.
  • Collaborative team/co-principal investigators: Complete the table with the following information for each co-PI (minimum of one, maximum of two; do not include the Coordinating PI in this section). You may need to use the scroll bar at the bottom of the table to scroll right to view and to complete all fields. Alternatively, you can tab to move through and complete the fields. For each co-PI, please provide:
    • Co-PI name, Title/Position, Degrees, ORCiD ID (format: XXXX-XXXX-XXXX-XXXX), Email, Early Career status (faculty position for 0-6 years).
      • In the context of this RFA, we are defining early career investigator as someone who has been in their faculty role for zero to six years at the time of application, i.e. have started their first independent position between November 2013 and November 2019.
    • Organization Name, Country.
    • Type of organization (drop down menu: academic/non-profit, industry/company, government, other).
    • Tax ID: Enter your organization’s Employer Identification Number (EIN), as assigned by the Internal Revenue Service in the 9-digit format (XX-XXXXXXX; total of 10 characters). Foreign organizations or others who do not an EIN should enter 44-4444444.
  • Statement on Diversity and Equity: Describe how your proposal and team seek to promote diversity and equity in this project. Examples can include engagement with diverse cohorts/populations, participation of labs in underrepresented regions, or a focus on inflammatory diseases that are prevalent, or overrepresented among underserved global populations. Limited to 250 words.

• Project Proposal: Upload your project proposal as a single PDF; font must be 11 points or larger and margins must be at least one-half inch (top, bottom, left, and right) for all pages. Include the following sections:
  • Proposal Body: (750 words maximum) Summary of the project, which should include in three parts:
    • I. Scientific Goals of the Project: Define the scientific question or problem that the team aims to explore. Clarify the rationale for why it requires an interdisciplinary approach, has been historically difficult to address, and how the team is poised to clarify it.
    • II. Tools & Resources: Provide a summary of the tools, technology, and other resources that your team previously developed, aims to develop as a part of the project, and may hope to gain from others teams of investigators. This list should highlight resources you can share with other projects and those that you feel you would benefit having access to.
    • III. Team Contribution: Briefly describe the specific contributions of each participating lab.
  • Figures​ (optional): There is no requirement for preliminary data. This RFA is intended to stimulate new collaborations and scientific directions. If you would like to provide figures of any kind, limit to one page, inclusive of legends.
  • References​ Cited in your proposal (no word/page limit).
• Biosketches for Coordinating PI and co-PIs: Upload the biosketches in PDF format for the Coordinating PI and for each of the co-PIs. Biosketches can be uploaded in a combined single PDF or one PDF for each co-PI; maximum of five pages per biosketch; NIH format or similar.
• Budget (one page maximum per PI): Upload in PDF format; budgets can be uploaded in a combined single PDF or one PDF for each co-PI; one page maximum per PI; font must be 11 points or larger and margins must be at least one-half inch (top, bottom, left, and right).
  • Description can be at a high level and in narrative or tabular form, outlining costs for personnel, supplies, equipment, travel, subcontracts, other, and indirect costs.
  • Budget is a max amount of $175,000/lab total costs for the two-year duration. Indirect costs are limited to 15% of total costs. There is a firm cap of $350,000 or $525,000 total costs per team depending on whether there are two or three labs participating.
  • Indirect costs may not be assessed on capital equipment or subcontracts, but subcontractors may include up to 15% indirect costs of their direct costs.
  • Budget should be requested in US dollars.
  • International grantees must use all grant funds exclusively for activities conducted outside the United States of America. Travel expenses to the United States (including round-trip tickets and all activities conducted in the United States) should not be covered from the requested grant funds.
  • Application budgets must reflect the actual needs of the proposed project.
• Letters of Commitment: Upload a signed letter from each co-PI, briefly describing the role and contribution of the co-PI to the overall team and project. Letters should be in PDF format; letters can be uploaded in a combined single PDF or one PDF for each co-PI. A letter is not needed from the Coordinating PI.

The formatting and component requirements, including word and page limits indicated above, will be enforced by the review team. Any submitted materials that exceed the word and page limits or do not follow the requirements will not be considered during the application review process.

Questions?

For administrative and programmatic inquiries pertaining to this RFA, please contact sciencegrants@chanzuckerberg.com. For technical assistance with SMApply, please contact support@smapply.io or while logged into SMApply, click on the information ”i” link in the upper right corner and submit a help request ticket.

CZI will evaluate all applications for scientific merit and will seek independent expert review of applications. External reviewers will provide feedback on the entire proposal with a focus on the importance of the scientific direction described in research proposal. Final decisions will be made by CZI staff in consultation with our scientific advisors. 

There is no expectation of any specific number of awards, and the Chan Zuckerberg Initiative reserves the right to not recommend the funding of any applications. CZI does not provide feedback on decisions for unfunded proposals. 

Selection of awardees will be based on:

• The scientific quality of the proposal and the applicants; 
• Potential impact of the work on an interdisciplinary understanding of inflammation; 
• Degree to which the proposed work bridges scientific areas and brings new ideas to the field; and 
• Potential of the collaboration partners to contribute to a highly collaborative interdisciplinary network.

• Funds from this award are intended to support research activities. Grants are made to institutions on behalf of the named award recipients and reasonable flexibility on how these funds are utilized is allowed, provided that the funds are used to support research activities related to the project. Funded investigators will be asked to provide summary budgets at the time of award and during annual reporting.
• For awarded projects, financial statements and progress reports will be due at the conclusion of each grant year. Specific deliverable requirements will be outlined in the award notification. Investigators of funded projects will be required to participate in regular investigator meetings, including annual investigator meetings. Travel support for these meetings will be provided by CZI separately from the requested grant funds. A kickoff meeting for grantees is tentatively scheduled for the week of June 1, 2020.
• Grantees may obtain funds for their research from other funding sources, provided that there is no conflict with meeting the terms of the CZI award. Additional funding should be reported as an outcome on the annual and final reports.
• Unused research funds may be carried over to the following year and requests for no-cost extensions will be considered.
• Ethical conduct: CZI advocates the highest standards for the ethical conduct of research. In addition to requirements of their own countries, grantees should adopt procedures for the use of animals in research and for the ethical treatment of human subjects and tissue donors, including obtaining their written informed consent. CZI regards the policies of the National Institute of Health as a strong model for such procedures.
• Data, publication, and dissemination policies: To accelerate scientific discovery and collaboration, CZI supports a consent, sharing, and publication policy for open and rapid dissemination of research results, including methods, data and reagents, and a policy for software development that maximizes accessibility, reuse, and shared development. Under rare circumstances, exceptions to the above may be considered where there are specific situations that make meeting these goals impossible or counterproductive to the project.
  • Software code: CZI requires sharing of software code developed by its grantees to generally be made publicly available on GitHub (or a similar public service) under a permissive open source license (MIT, BSD 2-Clause, BSD 3-Clause, or Apache v2.0). All pre-existing and derivative code should be designed to be licensed under the most permissive license possible, given the licensing terms of the pre-existing code. All analysis packages must be released through the appropriate language-specific package manager (e.g., PyPi for Python, Bioconductor and CRAN for R) with documentation, example data, and interactive demos (e.g., Jupyter notebooks), and the use of Docker or similar container technologies to ensure portability and reproducibility. Software code supported by CZI should be archived for long-term digital preservation and citability, when applicable.
  • Content and data sharing: CZI is committed to developing and using platforms that disseminate data openly and freely. Any datasets either curated or generated through the proposal should be made publicly available and easily accessible through an appropriate data repository, when applicable, under an Open Definition conformant license. Control data that will contribute to the reference, should be submitted to the Human Cell Atlas Data Coordination Platform. Ideally data sets would not include personally identifiable information, but if they do, consent to sharing the data should be obtained. Metadata, documentation, and intended use cases, as appropriate should be made available under an Open Definition conformant license, preferably CC0 or CC BY/CC BY SA for content that requires explicit attribution. Single cell transcriptomic data that is openly consented and used as a reference should be submitted to the Human Cell Atlas Data Coordination Platform.
  • Publications: To encourage rapid dissemination of results, any publications related to this funded work must be submitted to a preprint server, such as bioRxiv, before the first submission to a journal. Experimental protocols should be made publicly available through a protocol sharing service, such as protocols.io. CZI requests that scientific publications, preprints, and presentations that result from this award acknowledge the project was supported by CZI funding.
  • Reagent sharing: Resources and reagents developed with this funding support should be available for rapid dissemination to the community, where possible in an accessible community repository, such as Addgene (for plasmids/DNA reagents/viruses) and Jackson Labs (for model systems lines), etc. This requirement applies to cell lines, transgenic organisms, plasmids/clones, antibodies, and other reagents.
  • Consent: All human tissues should be adequately and fully consented to permit full sharing of the resulting data and any resulting tools, in accordance with laws and regulatory requirements. Any desired exceptions to this policy must be identified at the time of application, and such requests may affect the application’s chance of success. We are aware that there may be circumstances where broad consent may be challenging, and in some cases consent may be subject to revocation; we encourage investigators to discuss these cases with CZI scientific staff.
  • Intellectual property rights: CZI does not require assignment of ownership to any data, published results, or any other intellectual property that results from the work funded by these grants, but will have the same rights generally granted to others in the permissive licenses described above. CZI supports and promotes policies that enable results and technologies to have the broadest reach and impact. To this end, all newly developed software should be made available through permissive open source licenses as described more fully above. Other technology and intellectual property rights (such as patents) should be made freely available for all academic and non-commercial use, and where intellectual property rights are commercialized, they should generally be subject to non-exclusive commercial licenses that enable broad availability and dissemination.
• Indirect costs are limited to up to 15% of direct costs. Indirect costs may not be assessed on capital equipment or subcontracts, but subcontractors may include up to 15% indirect costs of their direct costs.
• International grantees must use all grant funds exclusively for activities conducted outside the United States of America.
• Applications selected through this process will be recommended for funding through the Chan Zuckerberg Initiative Donor-Advised Fund (DAF) at the Silicon Valley Community Foundation (SVCF) or through the Chan Zuckerberg Foundation (CZF).

All submitted applications will be kept confidential, except (1) as necessary for our evaluation or to comply with any applicable laws; and (2) to the extent that the application is made public or available to others without a duty of confidentiality through no fault of CZI. Notwithstanding, successfully funded proposals may be made publicly available and/or shared with other grantees or collaborators. Unfunded proposals will remain confidential as provided herein; however, information, including brief summaries of the proposed projects, project metrics, and the types of organizations who have applied for funding, may be made publicly available in aggregate form. Application materials will not be returned to applicants.