Although Dr. Frankenstein created new forms of life in grisly experiments that relied on combining spare parts, Dutch researchers say they are now attempting to build synthetic life forms from the ground up, and potentially more efficiently than nature.
As life evolved on Earth, each step forward was built on the last, leading to increasingly complex but sometimes inefficient systems. Now, BaSyc (Building a Synthetic Cell) is a consortium of six research institutes working on perfecting the natural processes that give rise to life. In a pair of new papers, their research represents significant new steps in advancement toward that goal.
Crafting Synthetic Life
Since 2017, BaSyc has been working on creating a synthetic cell, the basic building block of life. A Gravity grant from the Dutch Ministry of Education, Culture, and Science, along with the Netherlands Organization for Scientific Research (NWO), provided €18.8 in funding to begin operations. Progress has been steady, with an estimated two to three years left in the program.
“The end game of the program is to construct synthetic life-like systems that can grow autonomously, divide, and sustain [themselves]. It will differ from known living cells but have these essential features,” University of Groningen Professor of Biochemistry and team leader Dr. Bert Poolman told The Debrief in an email.
Energizing Artificial Cells
Within living cells, mitochondria generate the energy they require to function, and in nature, hundreds of different elements make up that cellular powerhouse.
The BaSyc team is now streamlining nature’s design, reducing it to just five elements across a two-part artificial system. The advantage is rooted in knowing where the system design is headed, allowing the researchers to develop fine-tuned solutions at the most basic level, unlike evolution, which only builds on what came before, unable to turn back the clock and reconsider earlier choices.
Existing mitochondria work through a cycle of converting the molecule ADP to ATP, then back, releasing the energy cells run on. The system is housed in tiny cell-like sacs known as “vesicles.” The first vesicle in the loop absorbs ADP and the amino acid arginine through the sac walls before burning the arginine to produce ATP.
Spending the energy is an entirely different problem. During this process, another vesicle absorbs the ATP and reverts it back into ADP, releasing the energy needed to power work, like growth and cell division. The process completes when the second vesicle sends the ADP back to the first, resuming the cycle. The downside to reducing the many elements of mitochondria to five is that the system can only run on arginine, not the fats, sugars, or even other amino acids that can power animal cells.
The Negative Unit
Poolman’s other creation is a vesicle for creating a negative electrical charge, like an electric circuit. It uses a chemical process where positively charged proteins enter the vesicle, pushing other molecules like lactose toward the negative center. This process mimics the behavior of living cells. Additionally, further testing showed the vesicle capable of more complex feats. Adding enzymes in addition to lactose, the system oxidized the lactose sugar and created the coenzyme NADH.
Dr Pool explained some of the challenges his team faced during development. “The greatest obstacles are generally integrating modules and creating out-of-equilibrium conditions. Thus, the optimal conditions are not necessarily the same for different modules. In biology, this is ‘solved’ by evolution, and here, we engineer minimal systems that work best for multiple modules.”
Moving Towards Synthetic Life
While Poolman and BaSyc have made significant progress, more must be done before total synthetic cells are a reality. After the BaSyc program concludes in the next few years, its replacement is already lined up. NWO has extended another €40 million research grant to the follow-up program EVOLF, “Evolving Life from Non-life,” and plenty of work remains to be completed in this innovative field of research.
“We are still more than 10 years away from such a synthetic life-like system,” said Dr. Poolman “Meanwhile, we learn a lot of biological mechanisms and discover surprising properties that emerge when bringing biological components together.
“Properties that are not seen in the individual components and will be difficult to discover in complex living cells,” Poolman added. “It will teach us (provide us) with a blueprint of life (-like systems), which is something we are currently lacking.”
“One of the next steps is to integrate the module for proton motive force generation (Nat Commun) with that for ATP production (Nat Nanotech), which then performs in terms of metabolic energy conservation like mitochondria do but in a much simpler manner,” he says.
Poolman says that his team is currently also working on coupling the module that facilitates ATP production to lipid synthesis, which allows membrane expansion, adding that “we will soon integrate it with modules for cell division and protein synthesis, in collaboration with colleagues in NL and abroad.”
The team’s paper “Chemiosmotic Nutrient Transport in Synthetic Cells Powered by Electrogenic Antiport Coupled to Decarboxylation” was published on September 12, 2024 in Nature Communications. The second paper, “Synthetic Syntrophy for Adenine Nucleotide Cross-feeding Between Metabolically Active Nanoreactors” was published on October 21, 2024 in Nature Communications.
Ryan Whalen covers science and technology for The Debrief. He holds a BA in History and a Master of Library and Information Science with a certificate in Data Science. He can be contacted at ryan@thedebrief.org, and follow him on Twitter @mdntwvlf.