Dr Simon Webb
Applications accepted all year round
Self-Funded PhD Students Only
About the Project
A key feature of biological systems is the storage and transmission of information, which maintains the complex chemical networks and functions within cells. One key function is the manufacture of new biomolecules, and this project takes particular inspiration from the rough endoplasmic reticulum (RER). The RER is the factory complex of eukaryotic cells, where mRNA from the nucleus is read by the ribosome and translated into biopolymers (protein), which are then packaged into phospholipid vesicles for distribution within cells.
In this project molecular robots will be synthesised that can mimic the function of the RER; “reading”, transmitting and “writing” coded information on the molecular scale. These molecular robots will take a synthetic coding strand and convert the information stored in its primary sequence into a new class of manufactured molecular products, which will be stored in the lumen of phospholipid vesicles. We will apply these robots in biomimetic self-assembled structures (vesicles), exploiting designed molecular properties of selective recognition and switchable shape. The biomimetic system produced will employ both biological and non-biological chemistry within the two phases and three distinct environments of phospholipid vesicles.
The project will build on previous work that used conformational switching of α-aminoisobutyric acid (Aib) foldamers (folded oligomers) to transmit information.[1] These peptide oligomers fold into extended helices, and this helical conformation is very sensitive to molecular recognition at the N-terminus. For example, complexation of ligands to a binding group at the foldamer N-terminus causes a conformational switch that is relayed to reporter groups at the C-terminus, which is more than 2 nm distant.[2] Most recently we developed a foldamer that bound (“read”) an external ligand and transmitted this information to a reporting group, several nanometres distant and embedded deep in the bilayer of phospholipid vesicles.[3] Conformationally switchable oligomers such as these could be developed into molecular machines able to “read” a coding strand and transmit information to a “writing” head at the far terminus.
This project is a unique opportunity to combine supramolecular chemistry with biological chemistry and catalysis, and will provide the student with a wide range of training opportunities across the chemical sciences.
Contact for further Information
Informal enquiries should be directed to Dr Simon Webb, [Email Address Removed]
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.
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree or the overseas equivalent, in a related subject area.
References
[1] M. De Poli, W. Zawodny, O. Quinonero, M. Lorch, S.J. Webb, J. Clayden, Science 2016, 352, 575.
[2] R. A. Brown, V. Diemer, S. J. Webb, J. Clayden, Nature Chem. 2013, 5, 853.
[3] F. G. A. Lister, B. A. F. Le Bailly, S. J. Webb, J. Clayden, Nature Chem. 2017, 9, 420.