Developmental scaling of cell mechanosensitivity in epithelial tissue

Project Information

Scaling-Sensitivity

Grant agreement ID: 101020243

DOI

10.3030/101020243

EC signature date 7 September 2021

Start date 1 January 2022

End date 31 December 2027

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 2 132 471,00

EU contribution

€ 2 132 471,00

Coordinated by

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France

Periodic Reporting for period 2 - Scaling-Sensitivity (Developmental scaling of cell mechanosensitivity in epithelial tissue)

Reporting period: 2023-07-01 to 2024-12-31

Summary of the context and overall objectives of the project

How Does a Single Cell Become a Complex Organism?
Imagine a single cell growing into a fruit fly, a tree, or even a human being. How does this miraculous transformation happen? How do cells know when to divide, move, or change shape? These fundamental questions are at the heart of the Scaling-sensitivity ERC project, which aims to unravel the mysteries of how organisms develop and maintain their proper size and shape. Our research isn't just about satisfying scientific curiosity. It's crucial for understanding various diseases, including those stemming from abnormal cell growth and tissue organization, such as cancer. By studying how cells behave during normal development, we can gain insights into what goes wrong in disease states and potentially develop new treatments. Using fruit flies as our model system, we aim to discover how cells sense their size and respond to physical forces to form tissues that can perform specific functions. While fruit flies might seem far removed from humans, they share many fundamental biological processes with us. This makes them an ideal subject for studying complex cellular behaviors without the ethical concerns of human experimentation.
To study these microscopic processes, we employ a variety of advanced techniques:
1. High-Resolution Microscopy: We use cutting-edge microscopes, including a technique called Stimulated Emission Depletion (STED) microscopy, which allows us to see incredibly fine details within cells.
2. Optogenetics: This innovative approach uses light to control specific genes, allowing us to manipulate cellular processes with unprecedented precision.
3. Advanced Image Analysis: We use sophisticated computer programs to analyze the vast amounts of data generated by our experiments.
4. Computer Simulations: These help us predict how cells might behave under different conditions and guide our experimental designs.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

So far, we've made several exciting discoveries:
1. The Cellular Scaffold: We've explored how the cell's internal scaffold (called the cytoskeleton) reorganizes when exposed to physical forces. This reorganization affects overall cell behavior, particularly decisions about cell division or cell death.
2. Size Matters: We've found that both cell division and cell death rates are proportional to cell size. This discovery helps explain how tissues maintain the right number of cells.
3. Feeling the Squeeze: We've identified specific proteins that help cells sense and respond to mechanical forces from their environment.
4. Developmental Timing: We've gained insights into how the "biological clock" ticks during development, helping cells decide when it's the right time to divide or change their behavior. Our research has revealed how hormonal signals plays a crucial role in controlling developmental transitions i and how they interact with other signaling molecules and mechanical forces to orchestrate the complex dance of development.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

While our work focuses on fruit flies, the principles we uncover have broad implications. Understanding how cells sense their size and respond to forces is crucial for many areas of biology and medicine, including: (i) Knowing how tissues regulate their size could help us develop better techniques for growing replacement organs or healing wounds. (ii) Many of the processes we study, such as cell division and death, are dysregulated in cancer. (iii) By understanding normal development, we gain insights into what can go wrong, potentially leading to new therapies for developmental disorders.
While we've made significant progress, many questions remain. We continue to refine our techniques and explore new avenues of research. Each discovery brings us closer to understanding the fundamental processes that turn a single cell into a complex, functioning organism. Our work showcases the power of basic scientific research. By studying seemingly simple organisms like fruit flies, we gain insights that could help human medicine and our understanding of life.

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