Implementation of Synthetic Biology Principles in Immunology

Note: This is not a limited submission and is being announced as a courtesy only.

Chan Zuckerberg Biohub Network and the Chan Zuckerberg Initiative invite applications for two-year initial research projects that harness synthetic biology to revolutionize our understanding and treatment of immune-related disorders. This RFA represents a strategic investment in transformative research that has the potential to yield breakthroughs with far-reaching impact on public health.

Objectives of the RFA

This RFA invites applications proposing innovative strategies and methodologies that implement synthetic biology principles in the context of immunology. Areas of interest include, but are not limited to:
● Engineering immune cells with enhanced specificity, functionality, and controllability, including improved sensing, homing, and effector capabilities.
● Designing and developing synthetic bio-circuits to direct cell behavior, such as:
○ Controlling immune cell tropism or tissue localization
○ Supporting in situ detection of complex, multi-ligand patterns for the detection of emerging or pre-symptomatic diseases
○ Regulating immune cell states and responses, for instance, in relation to T cell exhaustion, maintenance of self-tolerance, or T cell activation thresholds
○ Allowing reporting of what immune cells have detected in a non-invasive fashion
● Constructing artificial or semi-synthetic immune systems for disease modeling, mechanistic discovery, and therapeutic screening.
● Developing modular systems for immune surveillance and non-invasive reporting, allowing engineered cells to communicate what they’ve sensed or responded to in real time.

Out of scope

Proposals not aimed at introducing complex synthetic biology constructs in cells are not consistent with the RFA. For example, CRISPR screens would not be considered to be in scope unless used as a first step to design novel biocircuit logic.

Eligibility Requirements

● Applications may be submitted by domestic and foreign nonprofit organizations, including public and private institutions, such as colleges, universities, hospitals, laboratories, units of state and local government, and eligible agencies of the federal government. For-profit organizations are not eligible to receive funding, but may be involved in projects as collaborators. All grants will be awarded to institutions, not individuals.
● An organization may submit more than one application.
● Each application should designate one Principal Investigator (PI) as the Coordinating Principal Investigator (Coordinating PI). The Coordinating PI will act as the administrative contact between us and all other PIs on the grant (Co-PIs). 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 institution. Note that institutions outside the U.S. may not subcontract to U.S. institutions, so please be mindful when selecting the Coordinating PI/institution.
● Teams may include a total of three PIs. Each application must have one Coordinating PI, but may designate up to three total PIs (one Coordinating PI and up to two Co-PIs).
● Principal Investigators may only apply to join and serve as Coordinating PI or Co-PI on one application. Participation in multiple projects as an unfunded collaborator is allowed and encouraged.
● PIs/Co-PIs on one application may be employed at the same or different institutions.
● PIs and Co-PIs must each be permitted to receive grant support from the organization with which they are applying. This criterion may be defined differently in different types of organizations. Examples of eligible positions are:
○ Tenure track faculty;
○ Non-tenure track faculty or staff scientists who lead a lab or are engaged in academic activities and are permitted to apply for grants by their institution;
○ Researchers with expertise in the relevant areas who are affiliated with or supported by an institution and permitted to apply for grants; and
○ Co-PIs from for-profit companies are permitted as long as no funds are requested to support them or their work.
● Early-career investigators are strongly encouraged to apply as Coordinating PIs and Co-PIs.

Application Instructions

We use SurveyMonkey Apply as our 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.

To complete and submit an application:
1. Go to https://apply.chanzuckerberg.com.
2. Register and/or log in.
3. Click on the Programs link in the upper right corner.
4. Find the Implementation of Synthetic Biology Principles in Immunology RFA and click More.
5. Click the green Apply button in the upper right corner. September 2025 | Page 8
6. Enter the title of your application. The project title is limited to 60 characters, including spaces.
7. Complete the sections described below and submit by no later than 2 p.m. Pacific Time / 5 p.m. Eastern Time on November 13, 2025.

The application consists of the following sections (called tasks in the grants portal): Coordinating PI Details, Organization Details for Coordinating PI, Project Details, Project Proposal, Budget, Biosketches for Coordinating PI and Co-PIs, and Letters of Commitment (optional).