Last weekend over 200 researchers met on MIT’s campus for a day and a half workshop to discuss the progress and future directions of mammalian synthetic biology. The third annual meeting was co-chaired by Ron Weiss (MIT) and Mo Khalil (Boston University) who along with the organizing committee put on a packed weekend of talks. The full program and other information can be found at mammalian-synbio.org.
We tweeted out some of the sessions (check out @PLOSSynbio) and others documented it on twitter including the organizers @MammalianSynbio, Swapnil Bhatia from Boston University @Pipette_Ninja, and @sgi_dna. SGI-DNA also posted a Storify of the twitter conversation surrounding #msbw3.
Some speakers would not be on your typical list of “synthetic biologists”, however you define that, but they all had something to contribute to the conversation on how mammalian synthetic biology can have an impact. Many speakers highlighted the applications to human health with sessions like “Stem Cells and Development” and “New Therapeutic Approaches”, but topics also reached out to topics like fundamental genetic regulatory circuits and policy surrounding synthetic biology. Speakers also ranged from graduate students, to newer faculty, to established field leaders.
The opening keynote was from Irving “Irv” Weissman from Stanford who is widely known for his work on stem cells. He shared how stem cells can be used to treat blood diseases and shared his experiences on the challenges to translate from an academic lab to a company. While Irv Weissman may not be labelled a synthetic biologist very often, his talk showcased the potential of stem cell therapy and tied in nicely to the session on “Stem Cells and Development”.
A session on RNA regulation brought us back to more fundamental research for mammalian synthetic biology with tools like RNA switches and circuits, predicting alternative splicing, and a reverse engineering approach that discriminates between direct and indirect connections in a biological network. Each of these tries to understand and engineer genetic regulation to expand what can be engineered in mammalian cells.
After a lunch break the “Metabolism and Production” speakers spoke on understanding and optimizing production of important biomolecules. Producing a molecule may sound simple but there are many challenges associated with the host cells that produce your molecule. Increasingly, people have realized that we need to understand impact of production on the host cell and impact of different pathways in the cell on production. Karen Polizzi approached glycoprotein production by engineering metabolic biosensors and building mathematical models to understand how to optimize the cells. Eriko Takano talked about synthetic biology as a tool for antibiotic production. She pointed out that many antibiotic production processes are naturally modular so they lend themselves to the design-build-test cycles of synthetic biology. Again computational modelling proved useful to identify the key problems and guide the the design-build-test of engineered cells. A student talk also highlighted the use of modelling and control experiments to understand why an activator might have indirect repression of non-targeted genes. A major reason seems to be that a strong activator can actually soak up needed cofactors that are needed to activate other promoters.
A key feature of all mammalian tissue is the physical structure and arrangement of cell types. For instance, a human or a cats or a mouse all start as a single fertilized egg but grow into an arrangement of cell types that are highly reproducible across a species but easily distinguishable between species. Researchers want to understand the factors that govern these multicellular structures to understand many diseases and allow engineering of complex tissues. Celeste Nelson presented work on her favorite organ, the lung, showing how physical forces can shape the tissue. Chris Chen also discussed the mechanical influence on cellular behavior. Interestingly, he showed how the stiffness of a matrix can have different effects on cellular fate in 2D or 3D. Cells attached to a stiff surface can behave very differently than cells stuck in a 3D stiff biomaterial. Beyond physical mechanics, cells can also self organize. Leonardo Morsut from Wendell Lim’s lab showed how synthetic notch receptors can be used to try and engineer new multicellular organization.
Some view the human microbiome as the last discovered human organ since many studies have connected it to human health. Along this line, a session was devoted to the human microbiome. This session featured researchers like Chris Voigt and Harris Wang who have focused more on engineering the microbes that can interact with humans like the normal microbiome. The engineered cells could supplement mammalian cellular function to improve human health.
Finally, the first day ended with a poster session of 34 accepted presenters from across the United States, China, and the UK.
Day 2 kicked off with Arlene Sharpe drawing more connections for moving benchtop discoveries to the patients who need new therapies. She has done a lot of work on the Programmed cell death protein 1 (PD-1) pathway which is now moving into the clinic with recent FDA approvals for PD-1 inhibitors in cancer immunotherapy. Understanding that PD-1 blocks T cell activation lead to drugs that block its function and therefore boost the human immune response to attack cancerous cells.
Wilson Wong from Boston University also touched on immunotherapy for cancer treatment but focused on developing “app” like functions in engineered cells for smarter cancer immunotherapy. In an exciting use of cellular ‘noise’, Leor Weinberger showed progress in identifying compounds that increase gene expression noise to improve redirection of cell fate for cells or viruses. A potential application is latent HIV that needs to be activated to be eradicated by antiretroviral therapies.
The final panel changed gears and covered the industry and policy perspectives on the field of mammalian synthetic biology. The field still has a lot of regulatory hurdles to figure out and it was interesting to hear from industry representatives, political scientist Ken Oye, and Nicholas Short who is researching the legal policy of intellectual property.
The workshop put together a broad range of talks related to mammalian synthetic biology into a day and a half of programming. As a synthetic biologist working in microbes, I still found a lot of interesting work to think about after the workshop. The talks really demonstrated the vast space of complexity but also potential functions for engineering biology. We’ll stay tuned for a fourth edition of this workshop and see you next year!