What comes to mind when you hear the word artificial? One might think about artificial flavor enhancers, about intelligent robots or perhaps even about cosmetic surgery. Effectively, many of the connotations linked to the word artificial are negative. Another cognate concept relates to the word synthetic, which introduces us to a scientific discipline that might not be our first association when thinking about the artificial: Synthetic Biology.
Synthetic biology, the field my work lies within, is at the heart of current biotechnological research and efforts. In recent years, scientists evolved from pursuers of a bare understanding of the world we live in towards creators of synthetic life. My PhD in the group of Prof. Thomas Ward focuses on a particular type of artificial enzymes, so-called artificial metalloenzymes (ArMs). Artificial proteins and other artificial cell components constitute the core of synthetic biology and artificial life.
What really is natural or artificial?
When I tell people about my work on artificial enzymes, I often get a wry look and comments about the importance of natural products and the transcendence of creation. But what actually defines natural or artificial?
Natural corn from 7000 B.C. consists of approximately 5–10 hard kernels. The corn we eat today, which most people might consider natural or even organic consists of more than 1000 kernels and is available in different colors. The boundaries between artificial and natural merge and the focus shifts towards determining the benefits of a new technology rather than questioning its presence and use. That being said, SynBio certainly requires precise ethical standards to prevent abusive applications. Just recently, the EU released restrictive regulations on the use of genetically modified organisms.
Targeted therapies with ArMs
To create an ArM, researchers either refunctionalize existing enzymes or employ rational design and directed evolution to reveal various new-to-nature reactions. The goal is to enhance existing reactions or assemble new protein structures. An example of this is my PhD project which focuses on incorporating unnatural amino acids into ArMs. Other objectives in the Ward group focus on hijacking the function of an existing protein to create new features.
A good example of an application is chemotherapy. To this date, chemotherapeutic drugs are not very specifically targeted. On a given treatment course, all dividing cells are typically killed, which is exemplified by hair loss since hair cells divide frequently. There are, however, features that explicitly characterize cancer cells: certain proteins are highly abundant exclusively on the surface of cancer cells. If these could be hijacked and combined with a chemical catalyst that specifically interacts with these proteins, we could achieve a local release of a chemotherapeutic drug in the surrounding tissues of cancer cells. This approach towards targeted therapy represents one of many elegant solutions that synthetic biology has to offer to current challenges of clinically relevant research.
The art in artificial
It turns out there is a lot of art in artificial. These days, artificial cell components and whole synthetic cells are designed rationally and creatively. Examples of research achievements include DNA origami, music-generating plants or artificial colorants from color-producing bacteria. In the world`s most renown annual synthetic biology competition, which culminates in the finals at MIT (iGEM), students design synthetic microorganisms by de novo assembling so called biobricks, like assembling a LEGO model.
Thereby, they create futuristic bacteria for ambitious tasks like UV sensing, heavy metal biodetection, CO2 fixation, advanced infection and cancer diagnostics, environmental pollutant deactivation and many more. Synthetic biology combines creative human artefacts with functionality and design to tackle current health, climate and technological issues.
The potential of synthetic life
Synthetic life has the potential to create biodegradable plastics, clean up pollution, fight disease and pathogens, warn us about environmental threats, advance diagnostics and therapy and help us with everyday tasks.
To enhance this development, the University of Basel, together with ETH Zurich, heads the National Centre of Competence in Research (NCCR) in Molecular Systems Engineering (MSE). This cluster combines expertise from chemistry, biology, physics, bioinformatics and engineering to design and program molecular factories.
Besides bringing together different disciplines, the NCCR MSE is also very active in public outreach. The other day, an artist visited the labs to paint our researchers performing everyday tasks. Another interdisciplinary format is the lab concerto, where musicians perform in the lab while researchers of the Ward group show exciting experiments to the public. The NCCR MSE effectively communicates science by sparking the audience’s interests with events of a different kind.
The future will most certainly bring synthetic biologists, designers, artists and social scientists together to combine bioengineering with design and art and create a world where the artificial and the natural blend in harmony.
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