Artificial molecular machines for transmembrane communication

A Crick funded PhD position for the 2022 programme in the lab of Charlie McTernan.

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Applications for the 2022 PhD programme are now open until 12:00 noon GMT, Thursday 11 November 2021.

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Project background and description

 

We are a synthetic chemistry group working in supramolecular and biological chemistry, and nanotechnology. We work in the Francis Crick Institute in London, and at King's College London.

Our research looks at how we can apply Supramolecular Chemistry in Biological settings. Supramolecular Chemistry is the study of intermolecular, non-covalent interactions. These non-covalent interactions are critical to protein folding, DNA base pairing, and cellular signalling. Supramolecular Chemistry applies these same principles to create artificial systems capable of performing complex tasks [1-3].

The McTernan Group aims to apply recent breakthroughs in artificial molecular machines and metal-organic capsules in biologically relevant settings. We work with rotaxanes, catenanes and capsules to synthesise functional architectures, creating de novo catalytic enzyme analogues, artificial cellular receptors, and generating targeted drug delivery vehicles.

Supramolecular Chemistry is often inspired by the functionality and complexity of nature. Whilst great strides have been made towards achieving artificial analogues of biological molecular machines, synthetic systems have been unable to match the specificity and directionality vital to the concerted processes of biology.

This PhD project will develop new tools to bridge this gap, creating artificial molecular machines able to span, and transfer information across, biologically relevant membranes [4, 5]. The successful candidate will gain synthetic skills working with macrocycles, rotaxanes, vesicles. You will become expert in cutting-edge supramolecular chemistry, investigating guest binding, complex formation, and membrane insertion. You will gain skills in interpreting NMR spectra, organic synthesis, supramolecular chemistry, fluorescence spectroscopy, ITC measurements, vesicle extrusion, and mass spectrometry.

By creating new ways to transfer information across membranes, you will create a new generation of synthetic cellular receptors. In the longer term, your work will provide new ways to repair and, eventually, replace, faulty biological systems, and so to treat intractable diseases.

 

 

Diagram

 

Candidate background

 

This project would suit candidates with a background in chemistry or biochemistry, and an interest in working at the interface between disciplines. An interest in organic synthesis would be an asset, as would a willingness to learn new techniques.

References

 

1.         Erbas-Cakmak, S., Leigh, D.A., McTernan, C.T. and Nussbaumer, A.L. (2015)

            Artificial molecular machines.

            Chemical Reviews 115: 10081-10206.

2.         Erbas-Cakmak, S., Fielden, S.D.P., Karaca, U., Leigh, D.A., McTernan, C.T., Tetlow, D.J. and Wilson, M.R. (2017)

            Rotary and linear molecular motors driven by pulses of a chemical fuel.

            Science 358: 340-343. PubMed abstract

3.         Fielden, S.D.P., Leigh, D.A., McTernan, C.T., Pérez-Saavedra, B. and Vitorica-Yrezabal, I.J. (2018)

            Spontaneous assembly of rotaxanes from a primary amine, crown ether and electrophile.

            Journal of the American Chemical Society 140: 6049-6052. PubMed abstract

4.         McTernan, C.T., Ronson, T.K. and Nitschke, J.R. (2019)

            Post-assembly modification of phosphine cages controls host-guest behavior.

            Journal of the American Chemical Society 141: 6837-6842. PubMed abstract

5.         McTernan, C.T., De Bo, G. and Leigh, D.A. (2020)

            A track-based molecular synthesizer that builds a single-sequence oligomer through iterative carbon-carbon bond formation.

            Chem 6: 2964-2973.