BaSyC consists of 7 interacting work packages (WPs):
WP0 – System Design In this WP, theoretical and computational models are developed on all levels of complexity. The aim is to converge on a feasible overall design of the system with continuous feedback from the experiments.
WP1 – Cell Fuelling The aim of this WP is to engineer a minimal metabolism in a sealed system that can supply the vesicle with energy, and building blocks to operate replication, transcription and translation, that can accomplish energy, redox, volume, and pH homeostasis, and that can synthesize lipids allowing the synthetic cell to grow and divide.
WP2 – DNA Processing In this WP, an information processing machinery will be built that can replicate its own genetic information, that can transcribe the DNA in order to generate the flow of mRNA for protein production, and that can synthesize/assemble ribosomes, which in turn produce the proteins allowing the synthetic cell to grow and divide
WP3 – Cell Division In this WP, we will engineer a force generating machinery for constriction and fission of a vesicle, which will be responsible for the division of the BaSyC cell.
WP4 – Spatio-Temporal Integration WP4 will be devoted to integrating the base modules from WP1-3. In addition, strategies and machineries will be devised for the spatio-temporal control of the three base modules.
WP5 – Towards Autonomy In this WP, we will synthesize a whole genome supporting the functional modules as explored in WP1-4. We will apply an iterative cycle of genome design, assembly and testing.
WP6 – Philosophy, Ethics, and Public Debate Throughout the project, we will reflect on philosophical aspects, ethical dilemmas as well as societal opportunities associated with creating synthetic life, raise awareness with our researchers on these topics, and actively engage in public debate.
Each Work package is subdivided in a number of projects, as shown in this table.
Project | Title |
WP0 | System Design |
WP0.1 | Identification of global variables and constraints |
WP0.2 | Development of models for subsystems |
WP0.3 | Integrating models ultimately leading to an in silico synthetic cell |
WP1 | Cell Fuelling |
WP1.1 | A system for ATP and redox homeostasis |
WP1.2 | Modules to provide the cell with essential nutrients |
WP1.3 | Synthesizing a functional, expanding membrane |
WP2 | DNA Processing |
WP2.1 | Replication |
WP2.2 | Transcription |
WP2.3 | Translation |
WP3 | Cell Division |
WP3.1 | Vesicle constriction |
WP3.2 | Vesicle fission |
WP4 | Spatio-Temporal Integration |
WP4.1 | Integrating different modules |
WP4.2 | Container control |
WP4.3 | Temporal control |
WP4.4 | Spatial control |
WP5 | Towards Autonomy |
WP5.1 | Genome design & assembly |
WP5.2 | In vitro analysis of operon functionality |
WP5.3 | A cellular chassis for module optimization |
WP5.4 | Towards an autonomous synthetic cell |
WP6 | Philosophy, Ethics, and Public Debate |
WP6.1 | Philosophical assessment |
WP6.2 | Bridging the science – humanities divide |
WP6.3 | Proactively exploring societal potentials and concerns |
In order to address the challenge of building the first synthetic cell from the bottom up, the BaSyC consortium will bring 17 principal investigators (PI’s) together in a truly interdisciplinary pool of cutting-edge expertise for the first time.
The researchers have complementary expertise, covering all aspects involved in this research, from biochemistry and biophysics to (genome) engineering and genetics, microbiology and theory and ethics and philosophical aspects. They share a common vision that the ability to build a synthetic cell from its basic constituents will result in a deep molecular understanding of life. They are renowned for their multidisciplinary research, bridging disciplines and bringing different fields together, and are highly committed to a long-term collaboration within the BaSyC programme and beyond.
Michelle G.J.L. Habets, Hub A.E. Zwart and Rinie van Est
Why the Synthetic Cell Needs Democratic Governance
1 December 2020, Trends in Biotechnology
https://doi.org/10.1016/j.tibtech.2020.11.006
Thijs Nieuwkoop, Max Finger-Bou, John van der Oost and Nico J. Claassens
The Ongoing Quest to Crack the Genetic Code for Protein Production
15 October 2020, Molecular Cell, 80, 2, 193-209
https://doi.org/10.1016/j.molcel.2020.09.014
Elisa Godino, Jonas Noguera Lopez, Ilias Zarguit, Anne Doerr, Mercedes Jimenez, German Rivas and Christophe Danelon
Cell-free biogenesis of bacterial division proto-rings that can constrict liposomes
30 September 2020, Communications Biology, 3, article number: 539
https://doi.org/10.1038/s42003-020-01258-9
Mahesh A. Vibhute, Mark H. Schaap, Roel J.M. Maas, Frank H. T. Nelissen, Evan Spruijt, Hans A. Heus, Maike M. K. Hansen and Wilhelm T. S. Huck
Transcription and translation in Cytomimetic Protocells Perform Most Efficiently at Distinct Macromolecular Crowding Conditions
25 September 2020, ACS Synthetic Biology, 10, 2797-2807
https://doi.org/10.1021/acssynbio.0c00330
Duco Blanken, David Foschepoth, Adriana Calaça Serrão and Christophe Danelon
Genetically controlled membrane synthesis in liposomes
28 August 2020, Nature Communications, 11, 4317
https://doi.org/10.1038/s41467-020-17863-5
Zhanar Abil and Christophe Danelon
Roadmap to Building a Cell: An Evolutionary Approach
19 August 2020, Front. Bioeng. Biotechnol, Volume 8, Article 927
https://doi.org/10.3389/fbioe.2020.00927
Max Finger-Bou, Enrico Orsi, John van der Oost and Raymond H. J. Staals
CRISPR with a Happy Ending: Non-Templated DNA Repair for Prokaryotic Genome Engineering
17 June 2020, Biotechnology Journal, 1900404
https://doi.org/10.1002/biot.201900404
Weria Pezeshkian, Melanie König, Tsjerk A. Wassenaar and Siewert J. Marrink
Backmapping triangulated surfaces to coarsegrained membrane models
8 May 2020, Nature Communications, 11, 2296
https://doi.org/10.1038/s41467-020-16094-y
Eugene Kim, Jacob Kerssemakers, Indra A. Shaltiel, Christian H. Haering and Cees Dekker
DNA-loop extruding condensin complexes can traverse one another
4 March 2020, Nature, 579, 438-442
https://doi.org/10.1038/s41586-020-2067-5
Carsten F.E. Schroer, Lucia Baldauf, Lennard van Buren, Tsjerk A. Wassenaar, Manuel N. Melo, Gijsje H. Koenderink and Sieuwert J. Marrink
Charge-dependant interactions of monomeric and filamentous actin with lipid bilayers
4 February 2020, PNAS, 117, 5861-5872
https://doi.org/10.1073/pnas.1914884117
Elisa Godino, Jonás Noguera López, David Foschepoth, Céline Cleij, Anne Doerr,
Clara Ferrer Castellà and Christophe Danelon
De novo synthesized Min proteins drive oscillatory liposome deformation and regulate FtsA-FtsZ cytoskeletal patterns
31 October 2019, Nature Communications, 10, 4969
https://doi.org/10.1038/s41467-019-12932-w
Laura Restrepo-Pérez, Gang Huang, Peggy R. Bohländer, Nathalie Worp, Rienk Eelkema, Giovanni Maglia, Chirlmin Joo and Cees Dekker
Resolving Chemical Modifications to a Single Amino Acid within a Peptide Using a Biological Nanopore
19 October 2019, ACS Nano, 13, 12, 13668-13676
https://doi.org/10.1021/acsnano.9b05156
Tjeerd Pols, Hendrik R. Sikkema, Bauke F. Gaastra, Jacopo Frallicciardi, Wojciech M. Śmigiel, Shubham Singh and Bert Poolman
A synthetic metabolic network for physicochemical homeostasis
18 September 2019, Nature Communications, volume 10, Article number 4239
https://doi.org/10.1038/s41467-019-12287-2
Wojciech Mikołaj Śmigiel, Pauline Lefrançois and Bert Poolman
Physicochemical considerations for bottom-up synthetic biology
28 August 2019, Emerging Topics in Life Sciences, 3, 445–458
https://doi.org/10.1042/ETLS20190017
Siddharth Deshpande and Cees Dekker
Synthetic life on a chip
20 August 2019, Emerging Topics in Life Sciences, 3 (5) 559–566
https://doi.org/10.1042/ETLS20190097
Hendrik R. Sikkema, Bauke F. Gaastra, Tjeerd Pols and Bert Poolman
Cell Fuelling and Metabolic Energy Conservation in Synthetic Cells
05 August 2019, ChemBioChem, 20, 2581 – 2592
https://doi.org/10.1002/cbic.201900398
Siddharth Deshpande, Sreekar Wunnava, David Hueting and Cees Dekker
Membrane Tension–Mediated Growth of Liposomes
31 July 2019, Small, Volume15, Issue 38
https://doi.org/10.1002/smll.201902898
Weria Pezeshkian, Melanie König, Siewert J. Marrink and John H. Ipsen
A Multi-Scale Approach to Membrane Remodeling Processes
23 July 2019, Frontiers in Molecular Biosciences, Volume 6, Article 59
https://doi.org/10.3389/fmolb.2019.00059
Marten Exterkate and Arnold J. M. Driessen
Continuous expansion of a synthetic minimal cellular membrane
23 July 2019, Emerging Topics in Life Sciences, 3 (5) 543–549
https://doi.org/10.1042/ETLS20190020
Fabai Wu, Pinaki Swain, Louis Kuijpers, Xuan Zheng, Kevin Felter, Margot Guurink, Jacopo Solari, Suckjoon Jun, Thomas S. Shimizu, Debasish Chaudhuri, Bela Mulder and Cees Dekker
Cell Boundary Confinement Sets the Size and Position of the E. coli Chromosome
8 July 2019, Current Biology, 29, 13, 2131-2144
https://doi.org/10.1016/j.cub.2019.05.015
Hub Zwart
What is Mimicked by Biomimicry? Synthetic Cells as Exemplifications of the Threefold Biomimicry Paradox
July 2019, Environmental Values, 28 (5), 527-549
https://doi.org/10.3197/096327119X15579936382356
Alessio Fragasso, Sergii Pud and Cees Dekker
1/f noise in solid-state nanopores is governed by access and surface regions
27 June 2019, Nanotechnology, 30, 395202
https://doi.org/10.1088/1361-6528/ab2d35
Nico J. Claassens, Max Finger-Bou, Bart Scholten, Frederieke Muis, Jonas J. de Groot, Jan-Willem de Gier, Willem M. de Vos and John van der Oost
Bicistronic Design-Based Continuous and High-Level Membrane Protein Production in Escherichia coli
17 June 2019, ACS Synthetic Biology, 8, 7, 1685−1690
https://doi.org/10.1021/acssynbio.9b00101
Federico Fanalista, Anthony Birnie, Renu Maan, Federica Burla, Kevin Charles, Grzegorz Pawlik, Siddharth Deshpande, Gijsje H. Koenderink, Marileen Dogterom and Cees Dekker
Shape and Size Control of Artificial Cells for Bottom-Up Biology
10 may 2019, ACS Nano, 13, 5, 5439-5450
https://doi.org/10.1021/acsnano.9b00220
Siddharth Deshpande, Frank Brandenburg, Anson Lau, Mart G.F. Last, Willem Kasper Spoelstra, Louis Reese, Sreekar Wunnava, Marileen Dogterom and Cees Dekker
Spatiotemporal control of coacervate formation within liposomes
17 April 2019, Nature Communications, 10, 1800
https://doi.org/10.1038/s41467-019-09855-x
Marten Exterkate and Arnold J. M. Driessen
Synthetic Minimal Cell: Self-Reproduction of the Boundary Layer
13 March 2019, ACS Omega, 4, 3, 5293-5303
https://doi.org/10.1021/acsomega.8b02955
Hub Zwart
From primal scenes to synthetic cells
13 March 2019, eLife, 8:e46518
https://doi.org/10.7554/eLife.46518
Anne Doerr, Elise de Reus, Pauline van Nies, Mischa van der Haar, Katy Wei, Johannes Kattan, Aljoscha Wahl and Christophe Danelon
Modelling cell-free RNA and protein synthesis with minimal systems
9 January 2019, Physical Biology, 16, 2
https://doi.org/10.1088/1478-3975/aaf33d
Hub Zwart
Scientific iconoclasm and active imagination: synthetic cells as technoscientific mandalas
14 May 2018, Life Sciences, Society and Policy, 14, 10
https://doi.org/10.1186/s40504-018-0075-0