Science Forum: Building a community to engineer synthetic cells and organelles from the bottom-up

  1. Oskar Staufer  Is a corresponding author
  2. Jacqueline A De Lora
  3. Eleonora Bailoni
  4. Alisina Bazrafshan
  5. Amelie S Benk
  6. Kevin Jahnke
  7. Zachary A Manzer
  8. Lado Otrin
  9. Telmo Díez Pérez
  10. Judee Sharon
  11. Jan Steinkühler
  12. Katarzyna P Adamala
  13. Bruna Jacobson
  14. Marileen Dogterom
  15. Kerstin Göpfrich
  16. Darko Stefanovic
  17. Susan R Atlas
  18. Michael Grunze
  19. Matthew R Lakin
  20. Andrew P Shreve
  21. Joachim P Spatz  Is a corresponding author
  22. Gabriel P López  Is a corresponding author
  1. Max Planck Institute for Medical Research, Germany
  2. University of Groningen, Netherlands
  3. Emory University, United States
  4. Cornell University, United States
  5. Max Planck Institute for Dynamics of Complex Technical Systems, Germany
  6. University of New Mexico, United States
  7. University of Minnesota, United States
  8. Max Planck Institute of Colloids and Interfaces, Germany
  9. Delft University of Technology, Netherlands
  10. University of New Mexico, United Kingdom

Abstract

Employing concepts from physics, chemistry and bioengineering, 'learning-by-building' approaches are becoming increasingly popular in the life sciences, especially with researchers who are attempting to engineer cellular life from scratch. The SynCell2020/21 conference brought together researchers from different disciplines to highlight progress in this field, including areas where synthetic cells are having socioeconomic and technological impact. Conference participants also identified the challenges involved in designing, manipulating and creating synthetic cells with hierarchical organization and function. A key conclusion is the need to build an international and interdisciplinary research community through enhanced communication, resource-sharing, and educational initiatives.

Data availability

This Feature Article does not contain any primary data

Article and author information

Author details

  1. Oskar Staufer

    Max Planck Institute for Medical Research, Heidelberg, Germany
    For correspondence
    oskar.staufer@mr.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8015-3132
  2. Jacqueline A De Lora

    Max Planck Institute for Medical Research, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5599-7838
  3. Eleonora Bailoni

    University of Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  4. Alisina Bazrafshan

    Emory University, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3259-8196
  5. Amelie S Benk

    Max Planck Institute for Medical Research, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Kevin Jahnke

    Max Planck Institute for Medical Research, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7311-6993
  7. Zachary A Manzer

    Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8225-8990
  8. Lado Otrin

    Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5862-456X
  9. Telmo Díez Pérez

    University of New Mexico, Albuquerque, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Judee Sharon

    University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5691-0407
  11. Jan Steinkühler

    Theory and Bio-Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4226-7945
  12. Katarzyna P Adamala

    University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1066-7207
  13. Bruna Jacobson

    University of New Mexico, Albuquerque, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Marileen Dogterom

    Department of Bionanoscience, Delft University of Technology, Delft, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8803-5261
  15. Kerstin Göpfrich

    Max Planck Institute for Medical Research, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2115-3551
  16. Darko Stefanovic

    University of New Mexico, Albuquerque, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  17. Susan R Atlas

    University of New Mexico, Albuquerque, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1542-2700
  18. Michael Grunze

    Max Planck Institute for Medical Research, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2335-9513
  19. Matthew R Lakin

    University of New Mexico, Albuquerque, United States
    Competing interests
    The authors declare that no competing interests exist.
  20. Andrew P Shreve

    University of New Mexico, Albuquerque, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9567-3181
  21. Joachim P Spatz

    Max Planck Institute for Medical Research, Heidelberg, Germany
    For correspondence
    Joachim.Spatz@mpimf-heidelberg.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3419-9807
  22. Gabriel P López

    University of New Mexico, Albuquerque, United States
    For correspondence
    gplopez@unm.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5383-0708

Funding

National Science Foundation (CBET-1841170)

  • Gabriel P López

Max Planck Society (Max Planck School Matter to Life)

  • Joachim P Spatz

New Mexico Consortium

  • Gabriel P López

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Helga Groll, eLife, United Kingdom

Publication history

  1. Received: September 3, 2021
  2. Accepted: December 17, 2021
  3. Accepted Manuscript published: December 20, 2021 (version 1)
  4. Version of Record published: December 29, 2021 (version 2)

Copyright

© 2021, Staufer et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,439
    Page views
  • 192
    Downloads
  • 1
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Oskar Staufer
  2. Jacqueline A De Lora
  3. Eleonora Bailoni
  4. Alisina Bazrafshan
  5. Amelie S Benk
  6. Kevin Jahnke
  7. Zachary A Manzer
  8. Lado Otrin
  9. Telmo Díez Pérez
  10. Judee Sharon
  11. Jan Steinkühler
  12. Katarzyna P Adamala
  13. Bruna Jacobson
  14. Marileen Dogterom
  15. Kerstin Göpfrich
  16. Darko Stefanovic
  17. Susan R Atlas
  18. Michael Grunze
  19. Matthew R Lakin
  20. Andrew P Shreve
  21. Joachim P Spatz
  22. Gabriel P López
(2021)
Science Forum: Building a community to engineer synthetic cells and organelles from the bottom-up
eLife 10:e73556.
https://doi.org/10.7554/eLife.73556

Further reading

    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics
    Rajesh Sharma et al.
    Research Article

    Cyclic GMP-dependent protein kinases (PKGs) are key mediators of the nitric oxide/cGMP signaling pathway that regulates biological functions as diverse as smooth muscle contraction, cardiac function, and axon guidance. Understanding how cGMP differentially triggers mammalian PKG isoforms could lead to new therapeutics that inhibit or activate PKGs, complementing drugs that target nitric oxide synthases and cyclic nucleotide phosphodiesterases in this signaling axis. Alternate splicing of PRKG1 transcripts confers distinct leucine zippers, linkers, and auto-inhibitory pseudo-substrate sequences to PKG Iα and Iβ that result in isoform-specific activation properties, but the mechanism of enzyme auto-inhibition and its alleviation by cGMP is not well understood. Here we present a crystal structure of PKG Iβ in which the auto-inhibitory sequence and the cyclic nucleotide binding domains are bound to the catalytic domain, providing a snapshot of the auto-inhibited state. Specific contacts between the PKG Iβ auto-inhibitory sequence and the enzyme active site help explain isoform-specific activation constants and the effects of phosphorylation in the linker. We also present a crystal structure of a PKG I cyclic nucleotide binding domain with an activating mutation linked to Thoracic Aortic Aneurysms and Dissections. Similarity of this structure to wild type cGMP-bound domains and differences with the auto-inhibited enzyme provide a mechanistic basis for constitutive activation. We show that PKG Iβ auto-inhibition is mediated by contacts within each monomer of the native full-length dimeric protein, and using the available structural and biochemical data we develop a model for the regulation and cooperative activation of PKGs.

    1. Physics of Living Systems
    2. Structural Biology and Molecular Biophysics
    Enrico F Semeraro et al.
    Research Article Updated

    We report the real-time response of Escherichia coli to lactoferricin-derived antimicrobial peptides (AMPs) on length scales bridging microscopic cell sizes to nanoscopic lipid packing using millisecond time-resolved synchrotron small-angle X-ray scattering. Coupling a multiscale scattering data analysis to biophysical assays for peptide partitioning revealed that the AMPs rapidly permeabilize the cytosolic membrane within less than 3 s—much faster than previously considered. Final intracellular AMP concentrations of ∼80–100 mM suggest an efficient obstruction of physiologically important processes as the primary cause of bacterial killing. On the other hand, damage of the cell envelope and leakage occurred also at sublethal peptide concentrations, thus emerging as a collateral effect of AMP activity that does not kill the bacteria. This implies that the impairment of the membrane barrier is a necessary but not sufficient condition for microbial killing by lactoferricins. The most efficient AMP studied exceeds others in both speed of permeabilizing membranes and lowest intracellular peptide concentration needed to inhibit bacterial growth.