University of Manchester Featured PhD Programmes
University of Southampton Featured PhD Programmes
Birkbeck, University of London Featured PhD Programmes
University of Kent Featured PhD Programmes
University of Reading Featured PhD Programmes

Towards artificial signal transduction in living cells

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

The development of synthetic molecules able to transmit biochemical information across phospholipid bilayers could lead to a new type of synthetic biology, where the introduction of orthogonal signalling pathways leads to ‘short-circuiting’ of natural signalling networks in cells. G-protein-coupled receptors (GPCRs) are a key class of membrane protein that mediates cellular signal transduction, doing so through external ligand-induced conformational changes in helical transmembrane domains, which then triggers enzymatic cascades in the cell.

Foldamers (folded oligomers) comprising α-aminoisobutyric acid (Aib) have particular promise as mimics of GPCR function. These oligomers, which fold into extended 310 helices, have a conformation that is very sensitive to binding events at their N-terminus. For example adenosine complexation to a boronate-capped Aib foldamer in solution caused a conformational switch that was relayed to a reporter group at the far terminus, > 2 nm distant.[1] We have also developed light-switchable Aib foldamers able to relay photochemical information over similar distances within phospholipid bilayers, in a manner reminiscent of the light-sensitive GPCR, rhodopsin.[2] Most recently we developed a foldamer that mimics the behaviour of other GPCRs, transmitting binding information from an external ligand (Leu enkephalin) several nanometres into a bilayer.[3]

In this project, we will apply these promising biomimetic systems in a cellular context. Synthetic signal transducers (foldamers) that bear new fluorescent reporter groups will be chemically synthesised, which will be followed by studies of foldamer conformation and helicity switching in the membranes of living cells (fibroblasts). The signalling mechanism will be then linked to enzymatic activity, with a series of proteases and esterases used to transform non-binding or non-active signals into signalling molecules. If successful, this project may produce a synthetic link between exterior biocatalytic reactions and metabolism inside living cells.

Contact for further Information
Informal enquiries should be directed to Dr Simon Webb,
A formal application must be submitted to be considered for this project.
http://www.webblab.org

Funding Notes

Applications are invited from self-funded students or students who have funding in place and require an offer or to secure funding. For UK/EU tuition fees are £8,750 and International are £25,500 for 2019/20 academic year.

Qualification
Applicants should have or expect a good 2:i or 1st class honours degree (or the overseas equivalent) in Chemistry or a related discipline. Prior experience of catalysis and/or organic synthesis is advantageous but not essential.

References

[1] Brown, R. A.; Diemer, V.; Webb, S. J.; Clayden, J. Nature Chem. 2013, 5, 853.

[2] De Poli, M.; Zawodny, W.; Quinonero, O.; Lorch, M.; Webb, S.J.; Clayden, J. Science 2016, 352, 575.

[3] Lister, F. G. A.; Le Bailly, B. A. F.; Webb, S. J.; Clayden, J. Nature Chem. 2017, 9, 420.

Email Now

Insert previous message below for editing? 
You haven’t included a message. Providing a specific message means universities will take your enquiry more seriously and helps them provide the information you need.
Why not add a message here
* required field
Send a copy to me for my own records.

Your enquiry has been emailed successfully





FindAPhD. Copyright 2005-2019
All rights reserved.