Philipp Holliger

Information and function in synthetic genetic polymers
Group Leader page

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. We have also been able to construct the first all XNA nanostructures ([3] Chembiochem. 17: 1107).

The aim of this project is to expand XNA chemistry and function to explorethe informational, structural and catalytic potential of these novel genetic polymers with a view to advance our understanding of the parameters required for the molecular encoding of information and to use biostable “guide XNAs” to reprogram cellular function. Recently we have also been able to devise an RNA tripletpolymerase ribozymes and with it non-canonical reverse and primer-free modes of RNA replication ([4] eLife, 7:e35255).

Progress in this area has fundamental implications for the understanding of abiogenesis and the emergence of life, another active interest of the lab ([5] Science. 332: 209), and will provide a foundational technology for the generation of novel ligands, catalysts and nanostructures for applications in biotechnology and medicine.


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. Taylor, A.I., Beuron, F., Peak-Chew, S.Y., Morris, E.P., Herdewijn, P. and Holliger, P. (2016)
    Nanostructures from Synthetic Genetic Polymers.
    Chembiochem. 17 : 1107-10.
  4. Attwater J., Raguram A., Morgunov A.S., Gianni E. & Holliger P. (2018)
    Ribozyme-catalysed RNA synthesis using triplet building blocks.
    eLife, 7:e35255.
  5. Wochner, A., Attwater, J., Coulson, A. and Holliger, P (2011)
    Ribozyme-catalyzed transcription of an active ribozyme.
    Science. 332, 209-211.