Biocomputing with synthetic cells | 9am PT, Tues Feb 18, 2025

[Grigory Bronevetsky]

Modeling Talks

Biocomputing with synthetic cells Kate Adamala, University of Minnesota Twin Cities Tues, Feb 18, 2025 | 9am PT Meet | Youtube Stream Hi all, The presentation will be via Meet and all questions will be addressed there. If you cannot attend live, the event will be recorded and can be found afterward at https://sites.google.com/modelingtalks.org/entry/biocomputing-with-synthetic-cells More information on previous and future talks: https://sites.google.com/modelingtalks.org/entry/home 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.

[Grigory Bronevetsky]

Video Recording: https://youtube.com/live/JR7CR1iqFlM

Slides: https://drive.google.com/file/d/1sEYDZRAx4kXEC9at2dy_S_zG6SSOmjh2/view?usp=sharing

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