Amazing stuff!
I bet with machine learning & AI we will soon be able to considerably improve creating synthetic cells.
"It’s just a microscopic water droplet surrounded by a fatty membrane and stuffed with chemicals and snippets of DNA encoding a mere 36 genes. But it’s also arguably the closest researchers have come to building a living cell from scratch. In work ... show their creation, nicknamed SpudCell, can grow by fusing with other droplets, replicate its genome, and divide.
“This is a stunning scientific achievement,” ... But researchers note that SpudCell remains far from a living cell, as it can’t divide over many generations or evolve. ...
Researchers have long dreamed of creating cells in the lab, to both understand life’s fundamentals and produce cells that can be better engineered to make certain compounds. But most have set their sights lower and tried to replicate individual cell functions, such as feeding or growth. Putting multiple functions together has been extremely challenging, because each tends to work best under a different set of conditions, for instance a certain amount of magnesium or a specific level of acidity. “Being able to incorporate all of these modules together in a synthetic cell is the feat that the field has been waiting for,” ...
“But [the droplets] were never able to feed and divide based on their genome,” ..."
"The system contains 36 purified enzymes, a 90,000 base pair genome spread across nine separate DNA molecules, and a lipid membrane. SpudCell is able to grow, replicate its genome, divide, and undergo selection and competition across multiple generations.
Unlike earlier work on minimal cells that carved down living cells, SpudCell is built entirely bottom-up from individually purified, non-living components. It is the first time such a system has demonstrated a complete cell cycle.
What SpudCell demonstrates
Genetically controlled feeding and growth. SpudCell grows by fusing with small “feeder liposomes” that deliver lipids for membrane growth plus nutrients including ribosomes, enzymes, and small molecules. Fusion happens when a protein that SpudCell makes from its own DNA locks onto the feeder’s membrane, with the cell’s DNA directly controlling whether it can feed, how fast it grows, and how large it becomes. Natural cells make their own nutrients through metabolism, which requires hundreds of genes encoding metabolic enzymes. By feeding externally instead, SpudCell can complete a full cell cycle with a much smaller genome.
Division without cytoskeleton. Natural cells divide using internal scaffolding called a cytoskeleton. Building a functional cytoskeleton from scratch has been a major bottleneck in synthetic cell research because it requires dozens of proteins working in coordination. SpudCell sidesteps this entirely, with proteins crowding together on the membrane surface until the mechanical stress makes the membrane split. Cells that make more of this surface protein divide more efficiently, directly coupling the genome to reproductive success.
Selection and competition. When researchers introduced a genetic change that increased production of the fusion protein, cells with that change grew faster and produced more offspring. After five generations, the faster-growing variant had outcompeted the original. Under nutrient scarcity, the advantage increased. This demonstrates selection and competition operating in a fully synthetic chemical system. ..."
"... Much work remains to turn the construction of individual SpudCells into a true engineering pipeline. The cell’s seven DNA plasmids need to be consolidated into a single, more stable genome, and further molecular machinery needs to be built. ... there is also an infrastructure challenge, since different labs do not have shared standards for a working cell.
“This was exceptionally difficult work to scale,” ... “The knowledge in this space is very hard to explain, so we had collaborators on the project fly in for in-person demonstrations just to get particular techniques working. That’s not scalable. ..."
From the abstract:
"Cells are the fundamental unit of life. Yet there is no natural cell for which all its life-essential functions are understood.
Here we demonstrate a complete cell cycle for a synthetic cell undergoing selection, with genome replication, growth, resource acquisition via feeding, and genetically encoded division. The cell is encoded via a 90kb genome that includes functions needed for resource uptake, transcription, translation, growth, genome replication, and division. The resulting synthetic cell is sufficiently encouraging to support routinization of synthetic cell engineering workflows, and will ultimately underlie diverse applications across all of biotechnology."
For the First Time, a Cell Built From Scratch Grows and Divides | Quanta Magazine
Fluorescent microscopy of SpudCell - a synthetic cell assembled entirely from non-living chemical components - undergoing division.
