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From bacteria to artificial cells. The problem of self reproduction

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1 From bacteria to artificial cells. The problem of self reproduction
Albert Libchaber Rockefeller University Institute for Advanced Study

2 Model organism Bacteria: Escherichia coli (E. coli)
Well studied bacteria at normal conditions. Average size = 2mm Division time = 30 min, P=1atm, T=37oC ~1014 in 24 hours

3 Bacteria under pressure

4 Pressure dependence of doubling time
II I Growth rate decreases upon increasing pressure with a sharp decrease at high pressure.

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7 Recovery of MreB upon depressurization
t=0min t=270min t=390min t=500min t=590min t=1000min Kumar, Libchaber (preprint)

8 In his theory of automata John Von Neumann compared computing machines and living organisms.
The self reproduction of automata (1948), was discussed and linked to a Turing like principle. Von Neumann logic implied that self reproduction needed a memory and a code. This was proposed before Crick and Watson model of DNA.

9 J. Von Neumann Hixon Symposium 1951

10 This would follow Von Neumann logic for self- reproduction
Can we synthesize the most elementary cell size compartment that can self reproduce using genetic information only? This would follow Von Neumann logic for self- reproduction . J.Von Neumann Theory of self –reproducing automata (1966)

11 It is easy to encapsulate a cellular extract plus a DNA program into a phospholipid vesicle
Noireaux & Libchaber PNAS 101, (2004) Noireaux University of Minnesota

12 Cell-free Transcription-Translation system
A cellular extract • 1961: First cell-free protein synthesis study. The genetic code (Matthaei and Nirenberg) • 70s: Gene regulation unraveled with cell-free systems. • 90s: Invention of the efficient hybrid cell-free system (Spirin). - large scale protein synthesis. - high throughput proteomics. - protein evolution. - industrial applications.

13 Phage T7 Vincent Noireaux lab ● lytic coliphage.
● 40 kbp, 60 genes (35 with known functions). ● almost host independent (2 host proteins required). ● has its own RNA polymerase. ● has its own DNA polymerase.

14 Phage T7 synthesis in a test tube
Vincent Noireaux lab Phage T7 synthesis in a test tube Transcription Translation genome mRNA phage Replication ONLY ● TEM image ● 5-6 hours of incubation ● batch mode reaction J.Shin & V.Noireaux ACS synthetic biology 1, 408 (2012)

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18 geodesics A B C Y.T.Maeda, et al. ACS synthetic biology 1 (2011)
YFP-MreB Rhodamine-BSA Merged C Y.T.Maeda, et al. ACS synthetic biology 1 (2011)

19 Importance of the environment Rockefeller University
Microbes in the soil ecosystem Importance of the environment Alex Petroff , A.L Rockefeller University

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22 Conclusion Physics to Biology :
Duality: Sequence space versus object space Genetic code, Self Reference, Self Reproduction. Dangerous dynamics leading to a world of exponentials. Metabolism needs to follow. Darwinian evolution possible. The environment is a fundamental aspect of cellular life. It controls metabolism, development and organization. Research on artificial life is very active in laboratories.


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