Periodic Reporting for period 2 - EnBioSys (Energetics of Biological Systems)
Reporting period: 2022-10-01 to 2024-03-31
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 to infer the thermodynamic and energetic properties of living biological systems such as cells. Using this model to analyze the growth data of unicellular species from the last eight decades with find conserved features of unicellular energy usage and storage across the domains of life. A second important result constitutes a new paradigm in the intracellular organization of metabolism and energy transformation that is essential for the progression of early embryonic development.
In the first half of the project, we implemented the theoretical aspects and fundamentals of the energetics of biological systems. We have begun using this framework together with experimental approaches to establish methodologies to measure and understand the flows of energy and matter in biological systems. In collaboration with theorists, we have completed the theoretical aspects of Objective 1 and found the energetic costs and constraints required by the physical laws of unicellular growth across domains of life and environments. These results obtained for unicellular growth data are unexpected and certainly go beyond the state of the art. We believe that the application of our approach to mammalian cell growth and vertebrate embryonic development will open up fundamentally new views on cells and organisms’ function in accordance with the laws of thermodynamics.