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Manipulating Molecular Machines with Light and femto-Newton Forces

 

You will undertake the development of an optoelectronic microreactor-system of a new type that combines our single-molecule sensing approach with the ability of manipulating enzyme function in real time. Controlling single-molecule reactions is becoming feasible on optoplasmonic sensors. In this emerging area of optoplasmonics, light is shrunk to the length scale of molecules to probe single-molecule reactions. The light defines the nanoscale sensing and reaction volume thereby isolating for single-molecules. In this project, you will combine the optoplasmonic sensors with an optoelectronic microreactor to control enzyme activity. You will develop an new type of optoelectronic microreactor-system that will have the dual role of a) monitoring the enzymatic reaction in real time and b) exerting control over the reaction pathway. You will use temperature as well as optical gradient forces (optical  tweezers) to manipulate the enzyme activity and the reaction pathways. To achieve this goal, you will use a key component of the optoelectronic microreactor-system, a plasmonic nanoparticle that the enzyme will be attached to. You will use laser light to probe the nanoparticles plasmon resonance to detect the enzyme-substrate complex and its movements and conformational changes in real time. You will use the laser to apply optical forces on to the enzyme using the plasmonic near field enhancements. Applying very small, femtonewton (fN) forces offers the possibility of making some conformational states of the enzyme more likely than others, and this can be used to control enzymatic activity. You will use a secondary laser beam to rapidly cycle the temperature of the nanoparticle and with that implement on/off switch of the overall activity of the enzyme. In the second part of the project you will work in a larger team to apply the enzyme manipulation capabilities to DNA polymerase such as terminal deoxynucleotidyl transferase TdT in order to demonstrate a DNA ‘writer’, the de novo synthesis (‘writing’) of DNA.

 

We are looking for well-motivated students with a passion and strong background in biophysics, single-molecule techniques and optics; ideally the student should also have some experience with plasmonics and/or the use of optical tweezer, and with programming in Labview/Matlab/Comsol.

 

Please contact Prof Frank Vollmer for further information: f.vollmer@exeter.ac.uk

 

Please apply by May 02 here: Award details | Funding for prospective students | University of Exeter