Periodic Reporting for period 3 - EnBioSys (Energetics of Biological Systems)
Berichtszeitraum: 2024-04-01 bis 2025-09-30
All life depends on energy expenditure and requires a continuous supply of energy and matter in the form of nutrients to function within the second law of thermodynamics. To understand the fundamental principles of how cells and organisms function, we need to determine how nutritional energy is transformed by cellular metabolism and partitioned among the complex array of cellular processes life uses to stay alive, grow, and proliferate. To achieve these ambitious aims, this proposal aims to address three overall objectives:
1: Develop approaches and methodologies to quantify the overall energetics of biological systems
2: Elucidate the role of energy expenditure on the accuracy and reproducibility of cellular signaling
3: Determine how energetics drive embryonic development and cell growth
This work will overcome the current lack of non-invasive techniques to quantitatively measure the physical quantities of metabolism, especially rates of energy conversion and expenditure in biological systems. The results will yield quantitative thermodynamic data needed to fundamentally understand biological systems and will be essential for kinetic growth studies of normal and diseased systems.
1: Develop approaches and methodologies to quantify the overall energetics of biological systems
2: Elucidate the role of energy expenditure on the accuracy and reproducibility of cellular signaling
3: Determine how energetics drive embryonic development and cell growth
This work will overcome the current lack of non-invasive techniques to quantitatively measure the physical quantities of metabolism, especially rates of energy conversion and expenditure in biological systems. The results will yield quantitative thermodynamic data needed to fundamentally understand biological systems and will be essential for kinetic growth studies of normal and diseased systems.
To date, there are a couple of truly novel aspects to this project that have clear potential to constitute a significant breakthrough. One of the main results achieved from the project to date is the collaborative development of a minimal thermodynamic model and experimental approaches in our laboratory to infer the thermodynamic and energetic properties of living biological systems, such as cells and developing embryos. Using this model to analyze growth data from the last eight decades for unicellular species reveals conserved features of unicellular energy use and storage across the domains of life. A second significant result establishes a new paradigm for the intracellular organization of metabolism and energy transformation, which is essential for the progression of early embryonic development.
In the project, we implemented the theoretical and experimental foundations of the energetics of biological systems. We have begun using this framework, together with experimental approaches, to develop methodologies for measuring and understanding the flows of energy and matter in biological systems. In collaboration with theorists, we have completed the theoretical and experimental aspects of Objective 1 and found two thermodynamic rules that constrain the metabolic versatility of growing unicellular systems. These results obtained for unicellular growth data are unexpected and indeed go beyond the state of the art. We believe that applying our approach to mammalian cell growth and vertebrate embryonic development will open fundamentally new views of cells and organisms’ functions in accordance with the laws of thermodynamics.