Using synthetic biology tools can enable mammalian cells to communicate one-to-one, just as people do in a telephonic conversation

2. Bacchus W, Lang M, El-Baba MD, Weber W, Stelling
J & Fussenegger
Synthetic two-way communication between
mammalian cells
Nature Biotechnology, Published online 16/9/12

3. Introduction

4. Synthetic Biology of Animal Cells
Developments
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Switches
Logic gates
Timers, time-delay
circuits
Counters
Oscillators
Biocomputers
Recent successes
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Discovery of anti-TB
compounds
Design of bacteria that
kill cancer cells
Prosthetic network for
treating arthritis
Light-controlled
regulation of glucose
homeostasis

5. Cell-cell interactions
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enable cell populations to…
Communicate during development
Adapt to the environment
Form and/or recognize patterns
engineered cell interactions include…
Quorum-sensing dependent gene expression
Programmed pattern formation in yeast

6. Making the call

7. The two modules
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Sender cells communicate through the
essential amino acid L-tryptophan
Sender module: HEK-293 cells with pWB32, so
they constitutively express ß-subunit of E. coli
tryptophan synthase
Indole, present in media, was converted into
the signalling molecule – tryptophan
Receiver module: HEK-293 cells with pWB24 to
express a target-gene by L-tryptophaninducible sensor circuit

8. The modules at work

9. Characterizing the communication
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Sender (HEK-TrpB) and receiver (HEK-SEAP)
cells co-cultivated in varying ratios
Communication established only if ratio of
sender to total cell number is higher than
tryptophan uptake rate per cell divided by
tryptophan production rate of sender cell
Communication strength increase linearly with
receiver cell concentration
The response was indole-dependent

10. Validating the interactions
Heat maps showing ideal conditions for
maximum communication strength

11. Getting a call back

12. Cellular crosstalk
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Developed combined sender/receiver as well
as processor cells, creating a two-way, closed
loop feedback circuit
The cells (HEK-TrpB/SEAP) were engineered for
constitutive tryptophan synthase expression
and acetaldehyde-inducible SEAP expression
The processor cells, HEK-ADH, were transgenic
for L-tryptophan-inducible expression of
alcohol dehydrogenase to convert ethanol in
medium into acetaldehyde

13. The processing
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The L-tryptophan signal triggers expression of
reporter SAMY as well as production of volatile
acetaldehyde
The signal is broadcasted back to
sender/receiver cells which signal receipt of
message by acetaldehyde-triggered SEAP
expression
The system’s performance is quantized by
dynamically monitoring the reporter

14. Implementing two-way communication

15. A therapeutic call

16. Producing blood vessels
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VEGF and Ang1 act in a sequential and
complementary manner to produce blood vessels
The communication device was modified: VEGF
instead of SAMY and Ang1 instead of SEAP
Processor cells were engineered for constitutive
tryptophan synthase expression and acetaldehydeinducible Ang1 expression
The device programmed transient permeability
increase after 24h, correlating with VEGF
expression, and reversed after 48h by Ang1
expression

17. “
Such bidirectional and multistep communication
devices, inspired by naturally occurring fundamental
processes, are key to the design and construction of
next-generation synthetic mammalian networks that will
likely comprise populations of specialized cells
interconnected by orthogonal communication devices
to fulfill complex computational operations
’’

18. Thank you 