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Life-inspired complex molecular systems controlled by enzymatic reaction networks

Periodic Reporting for period 3 - Life-Inspired (Life-inspired complex molecular systems controlled by enzymatic reaction networks)

Période du rapport: 2022-10-01 au 2024-03-31

Living organisms have unique capabilities such as self-healing, adaptation to the environment, homeostasis, and converting chemical energy into motion, growth and division. Introducing aspects of autonomous function through sensing of the environment, monitoring the internal state, and regulating behaviour into synthetic life-inspired systems, represents a truly disruptive development, as it challenges our notion of what differentiates living systems from synthetic, man-made devices. However, despite substantial research efforts, a general platform for the construction of such systems remains a highly desired but elusive goal. How do we construct functional systems and devices out of molecules? How do we fuel these systems? How do we replace electronic circuits with networks of chemical reactions?

The ultimate aim of this proposal is to construct life-inspired complex molecular systems based on the design blueprints of living matter. Achieving this aim would yield life-like materials with embedded computing power that have the ability to sense their environment, to compute information from the environment, and to learn and adapt their shape and function. Such materials might become a radically new interface between electronic and living systems.
first of all, due to the corona pandemic, the hiring of new PhD students was delayed, which resulted in a somewhat lower degree of progress. However, in the first period we have made major progress in WP2, compartmentalization in hydrogel beads. We have also developed new in-house produced microfluidic reactors. We have now robust methods in place to immobilize enzymes on hydrogel beads, and characterize the enzymatic activity of immobilized enzymes in flow reactors. We are currently developing new methods based on Bayesian inference to rapidly extract kinetic information. These results are very encouraging and instead of developing networks described in WP1 using free enzymes, we will do this using immobilized enzymes as this system performs at a superior level.
As part of work in WP3, we are already investigating the construction of networks that resemble natural enzymatic reaction networks (mostly glycolysis and pentose phosphate pathway) to ensure that the outcome of the reaction will be biologically relevant molecules.
The immobilization of enzymes on microfluidically prepared hydrogel beads has proceeded faster and better than expected. Furthermore, the analysis of the enzyme kinetics using Bayesian inference is carried out using a new computational pipeline. Combined with the immobilization of enzymes, we will soon have a clear separation of 'hardware' (enzymes) and ' software' (peptides, small molecule substrates). We can therefore start to think about 'programming' these systems on a much more ambitious level than originally expected and we expect this to impact on the overall aims of the project.
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