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Projects

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

People

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.

Principal investigators (PI's)

PhD's, Postdocs and Research Assistants

  • The division of a cell is a key factor for the development of life. In my project, I study how the cell division mechanism present in many archaea (Cdv system) works in vitro. Understanding this system will allow us to reconstitute it inside of liposomes, to make them divide, and develop like this a cell division mechanism for the synthetic cell.

    Alberto Blanch Jover

    PhD
    Delft University of Technology - PI Cees Dekker
  • I am currently working on the genetic characterization of tetraether lipids in the archaeal strain Sulfolobus acidocaldarius. Not much is known about the lipid biosynthesis of tetraether membranes which confer extremophilic characteristics to archaea. Unravelling this information could help in engineering more robust membranes in other organisms and in synthetic cells.

    Alka Rao

    PhD
    University of Groningen - PI Arnold Driessen
  • Optical tweezers in combination with fluorescence provides a powerful tool to quantify nucleic acid processing by enzymes such as polymerases and helicases. Our aim is to be able to catch and manipulate a single nucleic acid strand between two trapped beads and to immerse this construct inside a GUV. This method would allow us to later measure and control nucleic acid processing activities of, e.g., a fully reconstituted replisome inside an artificial cell.

    Andreas Biebricher

    Postdoc
    VU Amsterdam - PI Gijs Wuite
  • A successful minimal cell model requires an optimized cell-like enclosed compartment which can efficiently perform fundamental living processes such as the ability to grow, replicate, and evolve. With this in mind, we aim to explore the development of a synthetic cell from an evolutionary perspective. We propose to use an in vitro directed evolution approach to recreate natural selection and introduce the ability to evolve as a must for building a minimal synthetic cell. Specifically, this project aims to establish the methodologies for i) genetic diversification ii) gene expression in liposomes iii) liposome screening/selection iv) DNA recovery and re-amplification. Moreover, directed evolution will be applied to improve the performance of fundamental biological modules such as Phi29 based DNA amplification and phospholipid synthesis enzymes as primary targets.

    Ana Restrepo Sierra

    PhD
    Delft University of Technology - PI Christophe Danelon
  • The aim of this project is to develop criteria for a productive dialogue on the synthetic cell between technoscience and civil society, and to analyse the views, expectations and concerns resulting from this. Special attention shall be given to the genres of imagination and the use of metaphors as structuring elements, as ways of highlighting promising or uncanny capacities of new technologies.

    Bettina Graupe

    PhD
    Radboud University - PI Hub Zwart
  • I work on the ‘in yeasto’ assembly of synthetic chromosomes, which means I investigate the use of the recombination machinery of baker’s yeast to construct synthetic chromosomes for a minimal cell. Additionally, I study mitochondria as models for minimal living systems.

    Charlotte Koster

    PhD
    Delft University of Technology - PI Pascale Daran-Lapujade
  • The aim of my research will be to investigate how a fully functioning synthetic cell will impact our understanding of life, technology and nature. Specifically I will assess both the epistemological commitments and the ontological dimensions underlying the concept of ‘life’ within synthetic biology. Finally I will also question where and if there is a divide between technology and nature in a time when both are assuming characteristics of the other.

    Daphne Broeks

    PhD
    Radboud University - PI Hub Zwart
  • Within the synthetic cell project, I am interested in coupling metabolic energy conservation with lipid biosynthesis

    Eleonora Bailoni

    PhD
    University of Groningen - PI Bert Poolman
  • the goal is to recreate synthetic cell division by reconstituting actomyosin cortexes in non-spherical liposomes.

    Federico Fanalista

    Postdoc
    Delft University of Technology - PI Gijsje Koenderink
  • The creation of a self-sustaining synthetic cell is intimately linked to the presence of an internal protein network and DNA, both participating in its mechanical response to loads. By means of optical tweezers and Acoustic Force Spectroscopy we are investigating the mechanics of isolated nuclei as simple biological systems which will help us to understand the mechanical contributions of such components to force response.

    Giulia Bergamaschi

    PhD
    VU Amsterdam - PI Gijs Wuite
  • In-vitro reconstitution of the actin-microtubule cross-talk during cell division

    Ilina Bareja

    Postdoc
    Delft University of Technology - PI Marileen Dogterom
  • Building a cellular chassis to test functional modules of a synthetic cell in-vivo.¬¬

    Joep Houkes

    PhD
    Wageningen University - PI John van der Oost
  • Control over chromosomal replication initiation is essential for a synthetic cell. In its absence, the copy number of the genome would constantly increase, leading to the redirection of all the available energy in the form of nucleoside triphosphates towards this process. However, due to the same essentiality that leads this research, testing modules to control this process is an hard task. In my project, I am looking to establish an in vivo platform allowing for an easy screening of different modules controlling this fundamental process

    Lorenzo Olivi

    PhD
    Wageningen University - PI John van der Oost
  • A synthetic cell, just like any other cells, must be able to grow and divide. In living cells division is mediated by a complex protein machinery which attaches to the cell membrane and actively exerts forces on it to deform the cell body. I aim to construct a minimal version of such a cell division machinery in vitro, taking inspiration from the actin cytoskeleton, a crucial player in eukaryotic cell division.

    Lucia Baldauf

    PhD
    Delft University of Technology - PI Gijsje Koenderink
  • An important hurdle in creating a synthetic cell is the incorporation of membrane transporters into the synthetic cell membrane. Without these transporters, key physico-chemical conditions cannot be controlled and any complex reaction network on the inside of a synthetic cell will eventually run out of fuel. Using microfluidics and cell-free transcription-translation, we hope to reconstitute the bacterial Sec translocase - which is responsible for membrane transporter insertion into the bacterial inner membrane - inside a synthetic cell membrane. This would not just be an important step towards an autonomous self-reproducing synthetic cell, but it would also provide a powerful new tool for the reconstitution and study of complex enzymatic pathways in vitro.

    Ludo Schoenmakers

    PhD
    Radboud University - PI Wilhelm Huck
  • My project concerns cell volume regulation through transport of compatible solutes

    Marco van den Noort

    PhD
    University of Groningen - PI Bert Poolman
  • We will focus on two important aspects of the computational framework underlying the synthetic cell project: To provide fundamental insight in the use of coacervates as a means to drive compartementalization of the cell, based on high-throughput coarse-grain molecular dynamics simulations. And to combine coarse-grain molecular dynamics models with Green's function reaction dynamics to bridge the molecular level to the system's level.

    Maria Tsanai

    PhD
    University of Groningen - PI Siewert-Jan Marrink
  • Previously, we engineered a phospholipid biosynthesis pathway based on a cascade of eight purified (membrane) proteins reconstituted into pre-existing liposomes. It starts with simple building blocks, fatty acids and glycerol-3-phosphate, to finally yield the two essential phospholipids phosphatidylethanolamine (PE) and phosphatidylglycerol (PG). Currently, we are further developing and optimizing the pathway.

    Marten Exterkate

    Postdoc
    University of Groningen - PI Arnold Driessen
  • The aim of my project is to insert newly synthesized protein into an expanding membrane using the Sec translocon.

    Max den Uijl

    PhD
    University of Groningen - PI Arnold Driessen
  • My PhD research is focused on the development of an out of equilibrium redox module to integrate within a synthetic cell-like system.

    Michele Partipilo

    PhD
    University of Groningen - PI Bert Poolman and Dirk Jan Slotboom
  • My current research project is focused on the generation of an artificial pH regulatory system in a reconstituted environment. Such system may guarantee optimal conditions for the performance of the metabolic pathways that constitute a synthetic cell.

    Miyer Fabian Patino Ruiz

    Postdoc
    University of Groningen - PI Bert Poolman
  • To achieve the construction of a bottom-up synthetic cell, one of the challenge lies in powering the cell. As a source of energy, an ATP synthesis pathway (arginine deiminase pathway) will be reconstituted in giant unilamellar vesicles (GUVs) together with the osmosregulatory protein OpuA. Because GUVs are micrometre-sized, experiments can be performed using light microscopy (confocal or wide field), providing new technical possibilities.

    Pauline Lefrançois

    Postdoc
    University of Groningen - PI Bert Poolman
  • The project aims to develop and implement a reliable method for spatially segregating genetic material after replication in a synthetic cell, in order to allow division. Starting point is the observation that the entropy of DNA-strands, which can be understood as polymers, can provide a force for segregation. The dependence of this process on the structure and the spatial organisation of the DNA in the cell will be investigated.

    Ramon Creyghton

    PhD
    AMOLF - PI Bela Mulder
  • Rob Joosten

    Research Assistant
    Wageningen University - PI John van der Oost
  • To construct synthetic cells from the bottom-up we need to build and study the complex genetic networks required to regulate them. Mathematical models serve as blueprints, used by experimentalist to engineer a regulatory network with a specific behavior in mind e.g. oscillations. We built a library of biological parts to be used by an evolutionary algorithm that can evolve mathematical models of large genetic networks towards any desired behavior. We test these networks in vitro and aim to use this design pipeline as a rapid prototyping tool for regulatory networks and as a stepping stone towards building a synthetic cell.

    Roel Maas

    PhD
    Radboud University - PI Wilhelm Huck
  • In one line of research, we’ll investigate the biophysical features of bacterial microtubules. In a second line of research, we will explore their potential functional role in an artificial cell; to do so, we need to explore the behavior of bacterial microtubules by investigating them in artificial cell-like containers (in vesicles and/or droplets).

    Reza Amini Hounejani

    PhD
    Delft University of Technology - PI Marileen Dogterom
  • My project focuses on the Min protein system, a pattern-forming system in E. coli. Min proteins perform pole-to-pole oscillations, exhibiting a concentration minimum at mid cell. This leads to the correct positioning of the Z-ring, which then initiates cell division. In our lab, we study Min proteins in a number of in vitro environments, which gives us control over critical parameters. Our goal is to gain a better understanding of the mechanisms underlying Min protein pattern formation.

    Sabrina Meindlhumer

    PhD
    Delft University of Technology - PI Cees Dekker
  • Sandrine D'Haene

    Technical Support
    VU Amsterdam - PI Gijs Wuite
  • My project focuses on development of synthetic metabolic pathways in E. coli for assimilation of one-carbon compounds, which can provide crucial insights for engineering core metabolism in a synthetic cell.

    Suzan Yilmaz

    PhD
    Wageningen University - PI John van der Oost
  • Creating an artificial cell, we strive to characterize and understand it as deeply as possible. Utilizing optical tweezers integrated with fluorescence spectroscopy and microfluidic techniques, I aim to build a system for in vivo manipulation of DNA. It will allow for a quantitative description of protein-DNA interaction inside the artificial cell during such fundamental processes of molecular biology as replication and transcription.

    Vadim Bogatyr

    PhD
    VU Amsterdam - PI Gijs Wuite
  • For the theoretical phase of the BaSyC (Building a Synthetic Cell) project, we are going to use this multi-scale simulation approach to decipher conditions of spontaneous membrane fission. Our aim is to find a minimal system, in which a vesicle spontaneously transform into a dumbbell-like shape. Then, an active process can split this structure into two vesicles, reminiscent of the cell division.

    Weria Pezeshkian

    Postdoc
    University of Groningen - PI Siewert-Jan Marrink

Support Office

Former staff

  • While cells try to maximize their growth rate, they do not exceed a maximum Gibbs energy dissipation rate to the environment. My project explores biophysical mechanisms at the molecular level that could explain this limit in cellular physiology, therefore linking both scales and providing another level of understanding of cellular functioning.

    Diego Alonso Martinez

    Postdoc
    University of Groningen - PI Matthias Heinemann
  • Does the temporal separation of lipid and protein production automatically facilitate cell division? We will study the effects of the temporal separation of lipid and protein production in budding yeast cell. Now we first focus on the mechanical effects. I will make a model to describe the effects of the separation on the mechanical properties of the cell wall, and then this mechanics may facilitate the cell budding.

    Ernest Yu Liu

    Postdoc
    University of Groningen - PI Matthias Heinemann
  • Gitta Buskermolen

    Postdoc
    AMOLF - PI Gijsje Koenderink

Publications

2020

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

2019

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

2018

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