Celebrating the Rise of Cell-free Systems in iGEM and Synthetic Biology
Cell-free systems provide a powerful tool to engineer novel systems without the constraints of living cells. These systems consist of the cellular machinery necessary for gene expression and protein synthesis, but without the presence of living cells.
Due to their inherent safety, simplicity and portability, cell-free systems have become an increasingly important tool in iGEM and synthetic biology more broadly, as they allow for rapid and efficient prototyping of genetic circuits and enable the development of new technologies for a range of applications.
Bearing in mind that they still have many shortcomings, mainly linked to cost, yield and reproducibility, cell-free systems offer several advantages. To begin, they allow for faster and easier prototyping of genetic circuits, allowing researchers to overcome the restrictions of working with living cells, such as the lengthy culture process and risk of contamination.
Cell-free systems allow for more precise control of the cellular environment, which can be important for studying the effects of specific genetic modifications. In addition, cell-free systems offer novel engineering capabilities, such as the ability to create biosensors or diagnostic devices that are not dependent on living cells, and to incorporate non-canonical amino acids and build systems that can tolerate toxic compounds.
Finally, although cell-free systems still raise biosafety and biosecurity concerns, they do offer advantages for biocontainment strategies by lowering biosafety risk when compared to living systems.
Cell-free Resources
At iGEM, our goal is to better enable teams to incorporate cell-free systems within their projects. To that end, we have compiled a number of resources on the iGEM Technology Cell-Free Systems webpage, including:
Coming Soon! We are creating a curated database encompassing all iGEM teams that have incorporated cell-free systems into their projects. See below for some examples.
A curated collection of 50+ videos and podcasts showcasing experiments and innovations in cell-free systems. These include public lectures, technical guidance and webinars from leading academia and industry stakeholders spearheading the development of the global cell-free systems ecosystem;
Information and links for educational resources, including BioBits™ – a portable, user-friendly, and inexpensive kit that uses freeze-dried cell-free technology for running biological experiments without living cells, and ECFK (Educational Cell-Free Kit) – a diverse toolbox suitable for demonstrating biological principles to groups that was developed by the 2017 EPFL iGEM team; and
Articles featuring the latest in the development and use of cell-free systems.
iGEM Team Examples
Cell-free projects have had a long history in the iGEM Competition, with the first project in 2007. Since then, multiple cell-free projects have made it to the finalists’ stage at the Grand Jamboree.
iGEM’s first documented cell-free project “Infector Detector” was created by the team from Imperial College London (UK) in 2007.
Imperial College London 2007 (United Kingdom) was the first team to successfully use cell-free technology for their project “Infector Detector”, a system for detecting biofilm infections on urinary catheters. Gold Medal, Undergrad Division.
Caltech 2014 (United States) compared the strength of the Anderson family of constitutive promoters in a TX-TL cell-free system and in living cells. Bronze Medal, Undergrad Division.
In 2017, the team from TU_Delft (Netherlands) won the Undergrad Grand Prize with their cell-free system to tackle antibiotic resistance in the dairy industry.
TU_Delft 2017 (Netherlands) engineered a cell-free system to tackle antibiotic resistance in the dairy industry. Grand Prize Winner, Best New Application Project, Best Entrepreneurship, Best Measurement, Gold Medal, Undergrad Division.
Munich 2018 (Germany) developed “Phactory”– a cell-free molecular assembly line for manufacturing bacteriophages for precision medicine. First Runner Up for the Grand Prize, Best Manufacturing Project, Best Entrepreneurship, Best Software, Bronze Medal, Overgrad Division.
In 2019, EPFL (Switzerland) won the Undergrad grand prize with their cell-free diagnostic test for detecting Flavescence Dorée, a highly-contagious plant pathogen plaguing European winegrowers.
EPFL 2019 (Switzerland) engineered a cell-free PURE system (Protein synthesis Using Recombinant Elements) to create a diagnostic test for detecting Flavescence Dorée, a highly-contagious plant pathogen. Grand Prize Winner, Best Environment Project, Best Integrated Human Practices, Gold Medal, Undergrad Division.
Stanford 2019 (United States) collaborated in a cell-free interlab study by demonstrating the functionality of the “ourTXTL” measurement standard for characterizing the relative strength of promoters in cell-free extracts, and implementing protocols for creating and lyophilizing cell-free lysis from E. coli and V. natriegens. Bronze Medal, Undergrad Division.
Thessaly 2019 (Greece) used a cell-free system for their point-of-care diagnostic for early detection of tuberculosis. Best Diagnostics Project, Gold Medal, Undergrad Division.
CSMU 2020 (Taiwan) developed a cell-free system for detecting oral cancer using saliva. Nominated for Best Diagnostics Project, Gold Medal, Undergrad Division.
In 2021, Marburg (Germany) won the Overgrad Grand Prize with “OpenPlast” – a cell free system from chloroplasts that can be used as a rapid prototyping platform for plant SynBio.
Marburg 2021 (Germany) created “OpenPlast” – a cell free system from chloroplasts that can be used as a rapid prototyping platform for plant SynBio. Grand Prize Winner, Top 10, Best Foundational Advance Project, Gold Medal, Overgrad Division.
Waseda_Tokyo 2022 (Japan) constructed a genetic circuit that detects progesterone and estradiol in two-channels using a cell-free protein synthesis system. Nominated for Best Foundational Advance Project, Gold Medal, Undergrad Division.
UBC-Vancouver 2023 (Canada) developed a modular, intein-mediated cell-free protein synthesis (CFPS) as an accessible and cost-effective tool for advancing scientific investigation. Silver Medal, Undergrad Division.
If you are an iGEM team with questions about using a cell-free system in your project, please contact us at cell-free [AT] igem [DOT] org. Tell us about your project, and we will do our best to help you out!
Or, if you want to help iGEM teams do just that, please contact us to learn how to get involved.
