Image: Professor Claudia Vickers, Chief Scientific Officer at Provectus Algae, an Australian biotech company taking synthetic biology to commercilisation. Synthetic biology could contribute to major breakthroughs in new fuels, improved agriculture, advanced manufacturing and health outcomes. Supplied.

For Dr Yu Heng Lau, bacteria are like tantalising boxes of microscopic Lego. Most bacterial cells host proteins that assemble themselves into cage-like compartments housing chemical reactions and metabolic processes. In his lab at the University of Sydney, Lau and his team are exploring how to re-engineer these protein cages into tiny factories that could manufacture new and improved medicines, materials and catalysts. 

One of Lau’s main projects is designing protein cages that can convert carbon dioxide into useful products such as biofuels. This involves building simpler, customised versions of the photosynthetic architecture found in cyanobacteria. “We basically want to mimic and improve on this natural process,” says Lau.

Getting this carbon-fixing hack to function in the real world requires a deep understanding of how biology works at its most basic level, says Lau. This means answering key questions, such as how enzymatic reactions behave inside protein cages and, ultimately, whether they can be planted inside a cell. “What we’re most interested in as a lab is understanding the fundamentals of how biology puts things together,” says Lau. 

Creating a nature-enhancing toolkit

Lau’s plug-and-play approach to solving health, energy and agricultural challenges is a textbook example of synthetic biology in action. Synthetic biology has its foundations in the 1953 discovery of DNA’s structure, and builds on the vision of scientists like Waclaw Szybalski in the 1970s to move from a “descriptive phase” (looking at the biology that exists) to a “synthetic phase” (devising and building whole new genomes). 

As recombinant DNA technology became more sophisticated, scientists moved on from simply transferring threads of genetic material from one organism into another and began modifying and combining sequences to program fresh biological functions. 

By the early 2000s, researchers began approaching biology like an integrated circuit, simplifying it so it could be easily tweaked or bolted together from scratch. Applying this classical engineering philosophy to living systems laid the foundation for creating standardised genetic building blocks, taking synthetic biology from a seemingly far-fetched idea to a platform technology.  

Today, thanks to massive advances in basic research into genetic engineering, synthesis and sequencing technologies in the past half century, synthetic biology is achieving these visions of functional systems built out of DNA, proteins and other organic molecules.  

Researchers working in this rapidly growing discipline are molecular biologists, geneticists and chemists, who are developing practical solutions ranging from mRNA vaccines for COVID-19 to plant-based meat that “bleeds”.

“We operate in these classical engineering faculties of design, build, test and learn,” says Professor Claudia Vickers, a molecular biologist who did her PhD at the University of Queensland and is now Chief Scientific Officer at Australian synthetic biology company Provectus Algae, a biotech startup specializing in the optimization of algae to produce high-value compounds for use in a wide array of industries. 

Fuelling the next biological revolution

The economic potential is huge. By 2040, this burgeoning field of science could generate $27 billion a year and create 44,000 jobs. Over the past two decades, Australian university science has fuelled the field’s meteoric rise from a fledgling discipline to a powerhouse already delivering real-world outcomes.

From the beginning, university students were breathing life into the new science. In 2007, students from the University of Melbourne were the fi rst Australian team to participate in the International Genetically Engineered Machine (iGEM) competition, which challenges students to use synthetic biology to solve problems, from developing new fuels to creating sustainable materials for fashion, and investigating drought resilience in crops.

Now, 20 universities include synthetic biology in their research programs. Ten of these are affiliated with the ARC Centre of Excellence for Synthetic Biology, headquartered at Macquarie University in Sydney. “It’s been really powerful and quite exponential in terms of building and growing the field in Australia,” says Vickers.

Synthetic genomes

While solving real-world problems is the driving force of synthetic biology, fundamental science is the engine powering it. To design a tailor-made biological circuit, researchers need to develop a set of rules that enable them to predict and control the components they’re working with. But unlike bolting together an electrical circuit, biology is often a mess of complexity and unknowns.

“If you don’t understand a system, it’s very hard to build it predictively,” says Vickers. “To do that, you need to understand the fundamentals of biology.”

For almost a decade, Dr Tom Williams has been busy trying to grasp the fundamentals of yeast, synthetic biology’s superstar organism. Based at Macquarie University, Williams is a research fellow working on Yeast 2.0 — an international consortium of universities building the first synthetic eukaryotic genome. 

Rather than synthesising the yeast genome in its entirety, Williams and his colleagues are figuring out how to create a stripped-down, minimal genome that includes only functional genetic components. This streamlined yeast strain will have a built-in system that allows non-essential genes to be deleted, inverted, duplicated or shuffled at the flick of a switch, paving the way for genetic combinations nature has never seen before. 

“Although we’re making one synthetic genome to begin with, we have the capacity to make infinite versions of it in the future,” says Williams, who completed his PhD at the University of Queensland in 2014, making him one of Australia’s first synthetic biology postgraduates.

Creating new fuels from scratch

Yeast is already an industrial workhorse, with US biotech company Ginkgo Bioworks tinkering with its genetic make-up to produce chemicals, pharmaceuticals, foods and other materials. Vickers is also stretching yeast beyond its traditional ‘beer, bread and wine’ capabilities, with her team exploring how it can be used to sustainably manufacture isoprenoids, the largest class of natural organic plant compounds, which are used to create valuable products like biofuels and industrial chemicals.

Once complete, the versatile Yeast 2.0 genome could be customised to create valuable products more efficiently than standard strains. Building the synthetic strain chromosome by chromosome could also help answer big questions in biology, such as how much genomes can be trimmed down.

While synthetic biology is set to become a handy tool for solving massive global challenges, fundamental research will remain at the heart of the discipline, particularly when it comes to training tomorrow’s bright minds, says Williams.

“Synthetic biology really builds on decades of fundamental research in genetics, biochemistry and microbiology,” he says. “On top of that, fundamental research trains the people that are required for the field to make an impact in industry.”

Writer: Gemma Conroy