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.
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.
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.