Philipp Holliger

Information and function properties 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 the chemical 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 recently to construct the first all XNA nanostructures ([3] Chembiochem. 17: 1107).

The aim of this project is to expand XNA chemistry and function to explore the 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.

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 ([4] Nature Chem. 7: 502; [5] Science. 332: 209), and will provide a foundational technology for the generation of novel ligands, catalysts and nanostructures with tailor-made chemistries for applications in biotechnology and medicine.


References:

[1] Pinheiro, V.B. et al (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] Mutschler, H., Wochner, A. and Holliger, P. (2015)
Freeze-thaw cycles as drivers of complex ribozyme assembly.
Nature Chem. 7, 502-8

[5] Wochner, A., Attwater, J., Coulson, A. and Holliger, P (2011)
Ribozyme-catalyzed transcription of an active ribozyme.
Science. 332, 209-211