Nov 7, 2022

Kate Adamala on Creating Artificial Life


Kate Adamala wants to make life from scratch! She is a Assistant Professor at the University of Minnesota. Adamala is a biochemist engineering synthetic cells.
Her research aims at understanding chemical principles of biology, using artificial cells to create new tools for bioengineering, drug development, and basic research. The interests of the lab span questions from the origin and earliest evolution of life, using synthetic biology to colonize space, to the future of biotechnology and medicine. Kate is a Founding member and one of the leaders of the Build-a-Cell collaboration.
 

I talked to her about the purpose of synthetic cells, how do they differ from biological cells and is it possible that they can interact with biological cells, what are the potential medical uses for synthetic cells and if synthetic cells can be used to grow a functioning human organ.

 Kate, what is the purpose of synthetic cells?
Synthetic cells can perform most of the same functions as natural biological cells, except they are more programmable. Synthetic cells have been used as therapeutics (to shrink tumors in live mice, to grow vasculature, to produce vaccines and even therapeutic viruses). Synthetic cells have also been used in biomanufacturing, for portable on demand production, for biocomputing, and to study natural processes like origins of life.
Generally, synthetic cells are thought to be more programmable and controllable than natural cells, which is the main rationale behind engineering them. Natural life is hard to control, cells are very complex and hard to understand. With synthetic cells, we don’t have that complexity, so it’s easier to build a cell with a specific function.



How do they differ from biological cells? Is it possible that they can interact with biological cells? Synthetic cells morphologically look very similar to natural cells: they have membrane, gnome, proteins etc. Some people engineer synthetic cells to look very much different than natural cells, for example people make cells without membranes (encapsulated inside droplets), but most applications use synthetic cells that look very similar to live cells.
Synthetic cells can interact with natural cells. It’s been shown that both synthetic and natural cells can exchange chemical and protein signals, communicating on the molecular level. For example synthetic cells could control protein production in natural cells, and the other way around: natural cell signals can be read by synthetic cells. 

What the potential medical uses for synthetic cells?
Synthetic cells are much more controllable than natural cells. We can understand exactly where every molecule goes, what every protein does, and what are the relationships between the design and function in synthetic cells. Natural cells are product of millions of years of evolution, so they are by necessity very complex. Synthetic cells are easier to work with, simpler and more programmable.
Medical applications include personalized therapies, where synthetic cell can be engineered to exactly match patient’s specific therapeutic needs. Synthetic cells could be program to reach specific site in the body (for example, a tumor site) and release therapeutic agents with great precision. Another application is in implants, where synthetic cells will provide interface between natural patient cells and an electronic implanted device. Synthetic cells are also used as models to study diseases, to help us understand healthy and diseased processes of natural cells, and to develop better drugs. 

Can synthetic cells be used to grow a functioning human organ? Could this be the future of transplantation?
 I don’t think this is the best application for synthetic cells. The whole point of engineering artificial cells is to make them simpler and more controllable than natural cells, and to build an organ you need very complex cells. I believe progress in transplantation will be easier achieved by engineering better methos to control natural cells. This is actually something synthetic cells could help with too, for example it’s been shown that synthetic cells can facilitate growth of natural organs. So yes, synthetic cells could help, but the final product transplanted into a patient will most likely remain made of natural cells. 


Have you ever tried to build multicellular synthetic „organisms“?
No, the technology is not there yet. Synthetic cells can communicate with each other, creating sort of proto-tissues, but it is a long way from a true multicellularity. 

Could the synthetic cells be used as a replacement to stem cells?
 Probably better way to do it would be to use synthetic cells to better program natural stem cells. Stem cells are very complex, as they need to turn into multiple natural cell types. As with the transplant question above: synthetic cells are designed to be simple, so they can be used to program natural cells but not to replace them in a patient.



What are your long-term goals? What is the maximum that you want to achieve in this field?
The long term goals are both practical application and foundational advancements. The practical applications are all the biomedical applications, therapies and manufacturing platforms I described above. With synthetic cells we hope to be able to better understand and control natural processes, making drugs and molecules that are hard to make with natural cells.
The foundational questions that we can answer with synthetic cells are some of the most fascinating research questions known: how did life start? why does life look like it does? how could like look like on another planet? Synthetic cells allow us to recreate evolution, in a way get a do-over of the origins of life but under very controllable conditions.
Building artificial life forms we can explore how life could look like if it wasn’t constrained by the environment of our own planet and all the evolutionary “dead ends” life encountered during its evolution on Earth. 

If you’re building artificial life then what being "alive" means?
The definition of life is a very tricky problem. I don’t have a good, authoritative and complete definition of life. I think the phrase used by the US Supreme Court Justice Potter Stewart is the best representation of our approach to defining life: “I know it when I see it”.

What is the most rewarding part of your job?
Doing research is incredibly rewarding, mostly because I can be the first person in the world to observe and understand some phenomena. Then there’s the incredibly fun aspect of working with students, mentoring people to become independent scientist. And the international community I am lucky to be a part of is great source of inspiration and ideas. Running a research group is a great privilege and responsibility, it’s the best job I can imagine. 

How did you get into this field?
 Th question of how life works, what makes chemistry become life, is one of the most fascinating questions researchers ever asked. I am trained as a chemist and a biologist, with expertise in synthetic biology. When I started my own lab, I was looking for the most interesting, fundamental question I could work on, while also developing practical applications that could help cure diseases and build a better economy. Engineering life from scratch allows me to work on this fascinating basic research problem, while at the same time doing something useful to the public. This is a very new field, with a lot of opportunities for growth, and the community of people working on those problems I very friendly and welcoming. I picked this as my research interest because I can’t think of a better, more rewarding and fascinating topic to work on.

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