Abstract:
Computation with biological logic gates promises bridging the gap between traditional hardware and living organisms. Boolean logic executed by biological circuits can offer advantages of life-like properties, including regeneration, self-replication and evolution. However, the first priority of any self-respecting live cell is to remain alive and to reproduce, which is often in conflict with requirements of stringent, pre-programmed logic gates. That's why biological computing in bacteria and other live cells is often unpredictable, natural cell gates are leaky and not very scalable.
Synthetic cells are emerging as an alternative to live natural cells for biocomputing, providing greater flexibility and engineerability. They combine advantages of complexity and enzymatic flexibility of live biology with in vitro simplicity. Synthetic cells offer a way to bridge natural biology with electronic devices, and to engineer bio-based tools with unprecedented accuracy and precision.
Bio:
Kate Adamala is McKnight Presidential Fellow Associate Professor at the University of Minnesota. Her research focuses on synthetic cell engineering, with the aim of understanding chemical principles of biology, using artificial cells to create new tools for bioengineering, medicine, and foundational 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 co-founder of the synthetic cell therapeutics startup Synlife, a Polymath Fellow of the Geneva Center for Security Policy, and co-founder and coordinator of the international synthetic cell engineering consortium Build-a-Cell. Lab info protobiology.org.
Summary:
Focus: biocomputing
Make cells with predictable behavior that can be driven to produce desired outputs
Logic gates: protein expression
Conditional on the state of the cell and other proteins attached to the cell
Can chain logic gates to create complex circuits
Key work is to develop synthetic cells that work much like a cell, but simpler and much more easily programmable
Traditional approaches
In vitro: biochemistry
Pro: Programmable and predictable
Con: No signal amplification 1 molecule = 1 photon
Con: Has to be built every time
Pro: Stays true to program
Pro: Arbitrary parts
Pro: Can be stored
Live cell: genetically encoded circuits
Con: Leaky gates
Pro: Signal amplification
Pro: Makes more of itself
Con: Evolves, changes
Con: Limited chemistry
Con: Dies, hard to store
New approach: Synthetic cells
Most Pros of in vitro
Plus signal amplification
Has to be built every time, which is more expensive but much safer
What is a synthetic cell?
A cell that doesn’t come from the chain of living cells currently in existence
Biochemical system with emergent properties
Hard to define!
Focus type of synthetic cell: Liposomal bioreactor that makes proteins
Has membrane, using same lipids as normal cells, or fatty acids for simple membranes
Using cholesterol to modulate membrane fluidity
Alternative: membrane-free cells using microfluidics
Cell-free protein expression
Applications:
Understanding natural biology
Biosafety & biosecurity
Origins of life
Space Exploration
Biocomputing
Diagnostics&Therapy
Tool development
Metabolic engineering
Use-case: teleportation of biology
Can specify the full ingredient list for making a cell and can create that cell in another location
Trumpet: Transcriptional RNS Universal Multi-Purpose Gate Platform
Boolean logic gate operations on DNA template with readout by fluorescent RNA aptamer
Single stranded DNA template string -> enzymatic reactions to generate RNA
100 bases
RNA polymerase promoter
Logic gate sequence
Readout area (fluorescent proteins bind to indicate gate is working)
RNA is fluorescent, so it can be seen by instruments
Implemented a NAND gate
0 or 1 input: fluorescent signal
Both inputs: no signal
Gate can support many individual inputs
Each input can have many possible values (maybe wildcards in the future)
The readout region can also produce an output molecule that is an input to the next gate
Supports major gates: NAND, NOR, AND, OR, NOT
Currently working on an adder
Application: biocomputing for space applications
Create aptamers that were sent to orbit and the reaction survived the space flight and worked in space
Build-A-Cell: www.buildacell.org