ACDC – Artificial Cells with Distributed Cores to Decipher Protein Function
Description
ACDC will employ a rapidly expanding living technology platform of transformational artificial cell technologiestowards the next generation of small molecule drug discovery, protein biophysics, and biochemical energyproduction. This will be executed through a future paradigm of sensory and synthesis regimes, based onprogrammable and re-configurable, (bio)chemical processes, built with precision, order, and as hierarchical cellularconstructs, in a design mirrored in living systems. In effect, we aim to emulate the structure and dynamics of livingcells and cellular tissues by embedding biochemical and biophysical systems capable of sensing, reconfiguration,synthesis, electrochemical gradient production and biochemical energy production - all essential processes of livingcells - built from the bottom up and middle-out approaches. We will accomplish this by producing microscale,liquid-based, chemical compartmentalisation (cores), with inter-compartmental (core-core) communication, just asone finds in organelles, cells and tissues. In the future, the resulting technology will enable creation of simplifiedartificial cell technologies based on cores as a platform for technical innovation, precisely for 1) the highthroughput screening of small molecule libraries against defined protein targets, such as membrane proteins, 2) thedefinition of precise biophysical aspects of targeted protein systems, 3) the elucidation of targets for futureantibiotics, 4) the definition of a scale-up of this core technology, and 5) the development of the multi-levelmathematics underpinning the complexity of such artefacts of living technology but also of natural living systems.ACDC will focus on developing this next generation technology through a detailed workplan that heavily involvesthe nontrivial tasks of integrating diverse state of the art technologies including microfluidics, microwaveresonators, DNA-based supramolecular assembly, in vitro gene expression and the integration of membranechannels into a functional platform. To exemplify the future potential of this integrated platform we will performinitial tests using high throughput screening of a small molecule library against the membrane protein target FeoBin phospholipid vesicles. Once demonstrated, a future implementation includes genetic mutation screening of ionchannels for high value targets. The development of in situ protein expression systems for expressing targetproteins, will be further applicable beyond screening and biophysical characterisation, to repurposing as bespokesensing and communication components. This will enable the creation of modular pathways within programmablecapsules for applications, in a future embodiment of this project, that includes using artificial cell technology asprogrammable and reconfigurable matter for specific applications including theranostics and personalizedmedicine, sensing and actuation in the environments for bioremediation, and discovery of potential antibiotics fromcomplex soil environments. All of these future applications will rely on the fundamental functionalities developedin ACDC including modular functional capsules, reconfiguration, remote read-out, core-core and core-environmentcommunication.We have assembled an international, interdisciplinary team from academia, industry and public engagementincluding expertise in engineering, physics, computer science, and chemical biology, to undertake this work. Ouroutreach and engagement programme will define the impact in both the public and economic sectors. Further,building upon 55 years of collective start-up enterprise experience, we will explore a new, agile, innovative vehicleto accelerate the translation of new intellectual property generated into commercial advantage and job creation forthe European Union.The overall objective of the ACDC project is to manufacture compartmentalised, liquid-based chemistries, asdiscrete, yet interactive and multifunctional cores, within micro-scale containment capsules as communicatingmicro-laboratories. Analogous to current ICT, we imagine the tremendous opportunities and potentialities that existwhen chemical and biochemical processes are miniaturized in programmable discrete units that provide on demandfunctionality. For example, we hope one day to be able to produce biochemical apps that could be installed in aportable chemical laboratory the size of a mobile phone that can then produce insulin, antibiotics or other highvalue medicines on demand. Another app could in principle detect toxins or disease in the environment or user.Another app would monitor daily nutritional parameters including mental or physical performance. As the firststeps towards that future vision, we aim to produce an artificial technological construct and process thatrecapitulates some aspects of living systems on the microscale, and therefore this project will produce exemplars ofsecondary living technologies concentrating on the wetware class [1] but also a multi-level mathematicalframework.
Key Data
Projectlead
Deputy Projectlead
Project team
Project partners
University of Trento; Cardiff University; Explora Biotech Srl; Elvesys SAS; Museo delle Scienze
Project status
completed, 03/2019 - 02/2023
Funding partner
Horizon 2020 / Projekt Nr. 824060
Project budget
730'000 CHF
Publications
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A chemical compiler for the synthesis of branched oligomers on standardized chemical reaction structures
2023 Weyland, Mathias S.; Flumini, Dandolo; Schneider, Johannes J.; Faggian, Alessia; Patiño Diaz, Aitor; Füchslin, Rudolf Marcel
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Exploring the three-dimensional arrangement of droplets
2023 Schneider, Johannes Josef; Weyland, Mathias Sebastian; Flumini, Dandolo; Füchslin, Rudolf Marcel
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Network creation during agglomeration processes of polydisperse and monodisperse systems of droplets
2023 Schneider, Johannes Josef; Faggian, Alessia; Patiño Diaz, Aitor; Li, Jin; Holler, Silvia; Casiraghi, Federica; Sanahuja, Lorena Cebolla; Matuttis, Hans-Georg; Hanczyc, Martin Michael; Barrow, David Anthony; Weyland, Mathias Sebastian; Flumini, Dandolo; Eggenberger Hotz, Peter; Dimitriou, Pantelitsa; Jamieson, William David; Castell, Oliver; Eschle, Patrik; Füchslin, Rudolf Marcel
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Obstacles on the pathway towards chemical programmability using agglomerations of droplets
2023 Schneider, Johannes Josef; Faggian, Alessia; Matuttis, Hans-Georg; Barrow, David Anthony; Li, Jin; Holler, Silvia; Casiraghi, Federica; Cebolla Sanahuja, Lorena; Hanczyc, Martin Michael; Eschle, Patrik; Weyland, Mathias Sebastian; Flumini, Dandolo; Eggenberger Hotz, Peter; Füchslin, Rudolf Marcel
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Artificial chemistry performed in an agglomeration of droplets with restricted molecule transfer
2023 Schneider, Johannes Josef; Faggian, Alessia; Jamieson, William David; Weyland, Mathias Sebastian; Li, Jin; Castell, Oliver; Matuttis, Hans-Georg; Barrow, David Anthony; Patiño Diaz, Aitor; Sanahuja, Lorena Cebolla; Holler, Silvia; Casiraghi, Federica; Hanczyc, Martin Michael; Flumini, Dandolo; Eggenberger Hotz, Peter; Füchslin, Rudolf Marcel
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Bidisperse extension of the kissing number problem
2023 Schneider, Johannes Josef; Barrow, David Anthony; Li, Jin; Weyland, Mathias; Flumini, Dandolo; Eggenberger Hotz, Peter; Füchslin, Rudolf Marcel
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Geometric restrictions to the agglomeration of spherical particles
2023 Schneider, Johannes Josef; Barrow, David Anthony; Li, Jin; Weyland, Mathias Sebastian; Flumini, Dandolo; Eggenberger Hotz, Peter; Füchslin, Rudolf Marcel
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Computational investigation of the clustering of droplets in widening pipe geometries
2023 Matuttis, Hans-Georg; Schneider, Johannes Josef; Li, Jin; Barrow, David Anthony; Faggian, Alessia; Patiño Diaz, Aitor; Holler, Silvia; Casiraghi, Federica; Sanahuja, Lorena Cebolla; Hanczyc, Martin Michael; Weyland, Mathias Sebastian; Flumini, Dandolo; Eggenberger Hotz, Peter; Dimitriou, Pantelitsa; Jamieson, William David; Castell, Oliver; Füchslin, Rudolf Marcel
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The good, the bad and the ugly : droplet recognition by a “shootout”-heuristics
2023 Matuttis, Hans-Georg; Holler, Silvia; Casiraghi, Federica; Schneider, Johannes Josef; Faggian, Alessia; Füchslin, Rudolf Marcel; Hanczyc, Martin Michael
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Ethical aspects of computational modelling in science, decision support and communication
2023 Füchslin, Rudolf Marcel; Ambühl, Jacques; Faggian, Alessia; Fellermann, Harold M.; Flumini, Dandolo; Geller, Armando; Hanczyc, Martin M.; Klinkert, Andreas; Krütli, Pius; Matuttis, Hans-Georg; Ott, Thomas; Scheidegger, Stephan; Schmid, Gary Bruno; Smieszek, Timo; Schneider, Johannes J.; Steiner, Albert; Weyland, Mathias S.
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Applied science : the curse and blessing of applying science
2022 Füchslin, Rudolf M.
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Influence of the geometry on the agglomeration of a polydisperse binary system of spherical particles
2021 Schneider, Johannes Josef; Faggian, Alessia; Holler, Silvia; Casiraghi, Federica; Li, Jin; Cebolla Sanahuja, Lorena; Matuttis, Hans-Georg; Hanczyc, Martin Michael; Barrow, David Anthony; Weyland, Mathias Sebastian; Flumini, Dandolo; Eggenberger Hotz, Peter; Füchslin, Rudolf Marcel
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Influence of the geometry on the agglomeration of a polydisperse binary system of spherical particles
2021 Schneider, Johannes Josef; Faggian, Alessia; Holler, Silvia; Casiraghi, Federica; Li, Jin; Cebolla Sanahuja, Lorena; Matuttis, Hans-Georg; Hanczyc, Martin Michael; Barrow, David Anthony; Weyland, Mathias Sebastian; Flumini, Dandolo; Eggenberger Hotz, Peter; Füchslin, Rudolf Marcel
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Computational approaches in biology
2021 Füchslin, Rudolf M.
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Modeling social systems at ZHAW
2021 Füchslin, Rudolf M.
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Introduction to the generation and analysis of networks of droplets : lecture at the ACDC Summer School, online, 27 August 2021
2021 Faggian, Alessia; Schneider, Johannes Josef
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Studying and simulating the three-dimensional arrangement of droplets
2020 Schneider, Johannes Josef; Weyland, Mathias Sebastian; Flumini, Dandolo; Matuttis, Hans-Georg; Morgenstern, Ingo; Füchslin, Rudolf Marcel
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Investigating three-dimensional arrangements of droplets
2020 Schneider, Johannes Josef; Weyland, Mathias Sebastian; Flumini, Dandolo; Füchslin, Rudolf Marcel
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Towards programmable chemistries
2020 Flumini, Dandolo; Weyland, Mathias S.; Schneider, Johannes J.; Fellermann, Harold; Füchslin, Rudolf M.