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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

Deputy Projectlead

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