Periodic Reporting for period 3 - NEPA (Non-Equilibrium Protein Assembly: from Building Blocks to Biological Machines)
Período documentado: 2022-01-01 hasta 2023-06-30
Better understanding of the fundamental principles of how life emerges at molecular scales could enable us to reprogram assembly phenomena in living organisms when needed, and can guide the design of functional biomimetic assemblies and bio-inspired nano-machines.
Protein assembly includes many interconnected effects that are difficult—or even impossible—to separate from one another in experiment. Luckily, proteins and protein assemblies still must obey the laws of physics and the principles of chemistry. The goal of my grant is to develop computer models, rooted in physics and chemistry, to discover the physical principles of energy-driven protein assemblies in the cell. I focused on the representative examples of the three main ways in which energy is supplied to protein assemblies in the cell: through chemical gradients, chemical reactions of energy-rich molecules, and mechanical forces. The predictions of my models are tested in experiments and used to explain experimental observations, in a close collaboration with experimental colleagues, to deliver an in-depth understanding of the molecular mechanisms that control the emergence of function in energy-driven protein assemblies.
The PI and the group have presented the above results at over 70 international meetings and institute/departmental visits across Europe and the US.
Using a combination of the above new methods, we have proposed physical mechanisms for how active elastic ESCRT-III filaments reshape cells in cell trafficking and cell division across evolution, and our predictions have been compared to and tested in experiments. We have proposed the physical mechanisms for collective self-organisation of mechanosensitive channels and their implications to cell volume sensing. We have identified a mechanism for passive transport of macromolecules in mechanical gradients. We have identified a new physical mechanism for the control of the size of protein assemblies, and used it to explain experimental data. We have developed a model for self-assembly in non-thermal fluctuating environments.