Why now?

In an era of unprecedented amount of data, we envision a paradigm shift in research through the integration of experiments with computational modeling. This will enable us to move beyond traditional reductionist approaches by developing unified frameworks for comprehending, predicting, and ultimately programming cellular behaviors.

​With our commitment to open science, we will provide the scientific community with cutting-edge tools, data, and platforms that significantly amplify our efforts to investigate, model, and uncover the principles of 3D cellular morphogenesis. This integrated approach will pave the way for groundbreaking discoveries and applications across various fields of biology and medicine. 

Transformative impact

With the CellScapes initiative, we are laying the groundwork for the next generation of cell biology research. Our work will empower researchers to ask new questions, extract meaningful insights, and ultimately rewrite our understanding of how cells shape life, which will further advance the study and treatment of human disease.

​Impact and applications:

• Fundamental research: Expanding our understanding of how cells achieve complex multicellular behaviors
• Developmental biology: Offering fundamental insights into early tissue formation
• Translational research: Developing new strategies for disease modeling, regenerative biology, and synthetic biology applications
• Open science: Democratizing access to tools and data through platforms like OME-Zarr and BioFile Finder

We will move from simply describing cell behaviors to actually understanding and programming them. The initiative will help answer key biological questions such as:

• What are the fundamental principles that drive multicellular morphogenesis? 
• How do groups of cells coordinate to form functional tissues?
• How do different cellular conditions/perturbations affect cell states and fate? 

Bridging the gap between experimental biology and computation

Through the integration of 2D & 3D stem cell models, quantitative experimental data, computational models, and synthetic biology, we will transform how we investigate cell behaviors.

​The CellScapes initiative will:

• Explore dynamic cell states through the development of experimental and computational models.
• Develop quantitative tools for describing and predicting cell behavior, including cell representations.
• Integrate live-cell imaging, AI, modeling, and theory to capture the dynamic nature of how cells change state.
• Engineer synthetic biological systems to test and refine our understanding of morphogenesis (what drives tissue formation).
• Offer our tools and data openly to support broader engagement in research and education efforts – ensuring everyone can benefit from our findings.

How it's different from other current research projects:

• From static to dynamic: Instead of fixed snapshots, we capture real-time cellular changes over time.​
• From descriptive to explanatory: We build models that anticipate cell behaviors, test predictions, and ultimately explain how and why behaviors occur.
• From observation to programing: We test our understanding by engineering cell state transitions and behaviors.

The Holistic Cell State Framework: An integrated approach

Decades of research have provided a comprehensive "parts list" of genes, proteins, and molecular pathways that govern cell behavior and function. However, understanding how these elements work together dynamically to drive collective behaviors remains a fundamental challenge. With breakthroughs in live-cell imaging, artificial intelligence (AI), and synthetic biology, we can now integrate data at multiple levels—from molecules to tissues—to develop models that explain and predict cell behavior. 

We offers a new paradigm—a holistic, dynamic, and predictive framework that integrates:

• ​Cell organization: The arrangement & interaction of molecules and structures inside a cell.
• Cell function: The actions and behaviors of a cell.
• Molecular census: A detailed inventory of all the molecules (and how many) inside a cell.
• Cell environment: The external environment of the cell including other cells.

Read more: Establishing a conceptual framework for holistic cell states and state transitions. Rafelski SM, Theriot JA. Cell, May 2024.

Our research strategy: from observation to predictive understanding

The CellScapes initiative follows an iterative research cycle—observing and measuring cell behaviors, modeling and predicting changes, testing hypotheses, and refining the framework toward understanding. We plan to execute this initiative with the following proof-of-concept projects.

Project 1: Observing, Measuring, and Modeling Multicellular Morphogenesis

​Studying Endothelial Cells in Flow Conditions (Under Shear Stress)
Using human induced pluripotent stem cell (hiPSC)-derived endothelial cells, we will explore how cells collectively respond to external forces such as shear stress (similar to blood flow). This will help us define key patterns of cell organization and adaptation while developing and testing the Holistic Cell State Framework to help define holistic cell states and transitions in a well-controlled, biologically meaningful context.

Project 2: Understanding the Shift from 2D Colonies to 3D Tissues

Investigating the Formation of Lumenoids
We will study how flat 2D cell colonies transition into 3D lumenoids—hollow, spherical, multi-cell structures that mimic tissue formation. Understanding how these structures emerge will provide insights into key morphogenetic processes that shape tissue development.

Project 3: Investigating Cell Plasticity Through EMT

Epithelial-to-Mesenchymal Transition (EMT) in Lumenoids
Cells naturally shift between different states during development, wound healing, and cancer metastasis—transitioning from an epithelial state to a mesenchymal and migratory state. By inducing EMT in lumenoids, we will investigate how cells reorganize, change behavior, and transition between these states. These insights will help refine our models of cell state transitions and improve our understanding of the factors that drive morphogenesis.

Project 4: Engineering Cell State Transitions to Program Cell Behaviors with Synthetic Biology

Build Programmable Synthetic Lumenoids (Synthoids)
To test our understanding of morphogenesis, we will introduce synthetic genetic circuits into lumenoids to precisely program collective behaviors, cell fates, and multicellular morphogenesis. This will serve as a proof-of-principle that we can not only predict but also engineer cellular programs—paving the way for applications in regenerative medicine and disease modeling.

Learn more about the Allen Institute for Cell Science

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