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A Double Dose: Steroid Dimers for Synthetic Signal Transduction


Department of Chemistry

Prof S Webb , Prof J Gough Monday, April 12, 2021 Funded PhD Project (Students Worldwide)

About the Project

We are familiar with the tools around us in the macroscopic world, from complex machines (e.g. computers) to simple components (e.g. rotors). There also exists a world of biological molecular machines (typically proteins) that operate in cells and mediate many of life’s fundamental processes. One of these processes is the transmission of information and molecules across the cell membrane, a protective barrier that is several nanometres thick. Specialised transmembrane proteins recognise external chemical messengers (‘signals’) and turn these into chemical information (‘reports’) inside the cell, in a process that usually involve a change in protein shape (conformation).

This project aims to use multi-nanometre long rigid-rod molecular rotors to develop a new way of transmitting information across membranes. These entirely artificial molecular rotors will be designed to change shape after binding to an external chemical ‘signal’. This shape change will transmit the information in the signal across both synthetic and natural membranes. This project will capitalise on recent work in the Webb group (published in Science and Nature Chemistry) that seeks to open a pathway towards synthetic signal transduction.

You will start with the chemical synthesis of a family of steroid dimers, each of which will bear a different ‘reporting’ group, such as a fluorescent dye, catalyst, and protein/enzyme inhibitor. After first characterising the behaviour of these compounds in organic solvents, they will then be studied in the membranes of simple cell mimics (phospholipid vesicles). As well as developing skills in synthetic and supramolecular chemistry, the project provides the opportunity to learn cell culture techniques in the Gough labs, as the last stage involves studying the behaviour of these molecular rotors in mammalian cell membranes. If successful, this system would lead to many exciting opportunities, for example providing artificial signalling networks that reprogram cells and produce fundamental scientific insights.

Academic background of candidates

Applicants should have or expect a good II(i) or 1st class honours degree (or an equivalent degree) in Chemistry or a related discipline. Prior experience of organic synthesis and/or supramolecular chemistry is advantageous but not essential.

Contact for further Information

Informal enquiries should be directed to Prof. Simon Webb,

A formal application must be submitted through the University’s online system to be considered for this project.

Webb group: http://www.webblab.org

Gough group: https://personalpages.manchester.ac.uk/staff/j.gough/


Funding Notes

This is a 3.5 year EPSRC studentship. Funding will cover UK tuition fees/stipend only. The University of Manchester aims to support the most outstanding applicants from outside the UK. We are able to offer a limited number of full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.
We expect the programme to commence in September 2021.

References

[1] R. A. Brown, V. Diemer, S. J. Webb, J. Clayden, Nature Chem. 2013, 5, 853.
[2] M. De Poli, W. Zawodny, O. Quinonero, M. Lorch, S.J. Webb, J. Clayden, Science 2016, 352, 575.
[3] F. G. A. Lister, B. A. F. Le Bailly, S. J. Webb, J. Clayden, Nature Chem. 2017, 9, 420.
[4] M. J. Langton, Nat. Rev. Chem. 2020, https://doi.org/10.1038/s41570-020-00233-6
[5] B. Rodríguez-Molina, M. Eugenia Ochoa, M. Romero, S. I. Khan, N. Farfán, R. Santillan, M. A. Garcia-Garibay, Cryst. Growth Des. 2013, 13, 5107.

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