Understanding how biological structures grow to reach and maintain their final size is a fundamental question in developmental biology, with far-reaching implications in health, disease, and aging. Despite decades of research, the mechanisms by which growth is constrained and ultimately arrested during development remain poorly understood, particularly from the perspective of energetics. Traditionally, studies on growth have focused on genetic and biochemical signaling pathways or mechanical forces; however, the energetic demands and limitations that underlie growth processes have received comparatively little attention.
This project aimed to fill that gap by investigating how energy metabolism constrains growth at the organismal and organ levels. Specifically, it focused on testing whether growth arrest during development is a consequence of internal energy limitations and how this ties into known scaling laws like Kleiber’s law, which predicts a sublinear relationship between metabolic rate and body mass. Using Drosophila melanogaster as a model, the project combined isothermal microcalorimetry, protein synthesis labeling, and high-resolution imaging to dynamically measure metabolic rates and growth in developing larvae and tissues.
The overall objectives of the project were:
To quantify how metabolic power changes during development in whole organisms and specific organs.
To test whether energy constraints drive growth arrest, through spatial limitations in transport networks (e.g. trachea), morphogen signaling gradients (e.g. Dpp), and mechanical feedback.
To determine whether metabolic rate scaling at cellular, organ, and organismal levels aligns with or deviates from established theories such as Kleiber’s law.
This research is strategically aligned with broader scientific and societal challenges, particularly in understanding the deregulation of growth in disease contexts such as cancer, cardiac hypertrophy, and developmental disorders. Growth arrest failures are hallmarks of cancer and many age-related diseases. By revealing how energetic constraints impact growth control, this project contributes crucial insight into physiological regulation mechanisms and offers new conceptual frameworks for addressing disease processes where these mechanisms go awry.
From a broader perspective, the potential impact of this project is twofold:
Scientific Impact: By integrating biophysics, developmental biology, and metabolic analysis, the project pioneers a truly interdisciplinary approach to growth regulation, offering new tools and perspectives that can be applied across model organisms and in disease models.
Societal and Clinical Relevance: Understanding how energy constrains growth opens new avenues for developing treatments that target metabolic pathways in cancer and aging. It also enriches fundamental knowledge that underlies future precision medicine strategies.
Finally, the project contributes to Europe’s scientific leadership by strengthening interdisciplinary research at the interface of biology and physics, supporting open science, and fostering career development and international mobility. Conducted at the IBDM and the Turing Centre for Living Systems (CenTuri) in Marseille, a hub for interdisciplinary research, the project exemplifies how combining experimental and theoretical sciences can lead to transformative insights into complex biological processes.
