Philipp Holliger

Information and function in synthetic genetic polymers
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Life is based on the capacity of the nucleic acids DNA and RNA to encode, store and propagate genetic information. However, whether their unique role in biology reflects evolutionary history or fundamental functional constraints, whether nature’s “choice” was shaped by chance or necessity, is currently unknown.

The Holliger lab uses synthetic biology approaches to explore these fundamental questions of biological form and function towards a better understanding of thechemical etiology of the genetic apparatus shared by all life on earth.

Previously we have shown that diverse synthetic genetic polymers (called XNAs), based on nucleic acid architectures not found in nature, can mediate both heredity and evolution, two hallmarks of life ([1] Science, 336: 341) as well as catalysis ([2] Nature, 518:427), another fundamental property of biopolymers.

Progress in this area has fundamental implications for the understanding of abiogenesis and the chemical constraints for the emergence of life, another active interest of the lab ([3] Nature Chem7:502; [4] Science. 332: 209; [5]eLife. 7: e35255).

Potential projects would be focused on these two general areas including 1) exploring the informational, structural and catalytic potential of novel genetic polymers with a view to advance our understanding of the parameters required for the molecular encoding of information and 2) advancing RNA-catalyzed RNA synthesis towards a system capable of self-replication and evolution.


References

  1. Pinheiro V.B., Taylor A.I., Cozens C., Abramov M., Renders M., Zhang S., Chaput J.C., Wengel J., Peak-Chew S-Y., McLaughlin S.H., Herdewijn P. & Holliger P. (2012)
    Synthetic genetic polymers capable of heredity and evolution.
    Science, 336, 341-44.
  2. Taylor, A.I., Pinheiro, V.B., Smola, M.J., Morgunov, A.S., Peak-Chew, S.Y., Cozens, C., Weeks, K.M., Herdewijn, P. and Holliger, P. (2015)
    Catalysts from synthetic genetic polymers.
    Nature, 518, 427-30.
  3. Mutschler H, Wochner A & Holliger P. (2015)
    Freeze-thaw cycles as drivers of complex ribozyme assembly.
    Nature Chemistry 7: 502-8.
  4. Wochner, A., Attwater, J., Coulson, A. and Holliger, P (2011)
    Ribozyme-catalyzed transcription of an active ribozyme.
    Science. 332, 209-211.
  5. Attwater J., Raguram A., Morgunov A.S., Gianni E. & Holliger P. (2018)
    Ribozyme-catalysed RNA synthesis using triplet building blocks.
    eLife, 7:e35255.