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  High throughput single molecule FRET for drug screening


   Department of Chemistry

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  Dr T Craggs, Prof Ashley Cadby  No more applications being accepted

About the Project

A Ph.D position is available under the Imagine initiative to develop a high through put single molecule FRET system in the Bio-Imaging center at Sheffield. This work will provide the basis for a new, disruptive technology which will revolutionize drug discovery. FRET allows us to measure the confirmation of molecules, specifically proteins, with angstrom precision. These confirmations are vital to the function of proteins, and by measuring the confirmation profiles of proteins in the presence of drug candidates we can identify suitable candidates for further investigation. Currently determining confirmation profiles using single molecule FRET is a slow process making its application to high throughput drug screening not viable. However, we have developed a method to multiplex single molecule FRET gaining a 1000-fold increase in speed, making the screening of 10K candidate compounds within 24 hours a real possibility. You will be working with two world leading groups, one in FRET (Craggs) and another in optical systems development (Cadby) to design, develop and apply the system to drug screening.

What will you do.
You will design and build a single molecule FRET microscope capable of detecting hundreds of single molecules simultaneously. This will require the development of high resolution optical paths and hardware programming to control the multiple aspects of the microscope. Once built you will design the data analysis and automation of the system with a view to scientific and commercial applications, exploiting the groups strong links with industrial partners.

Ideally, we want a self-motivated individual who is not afraid of new challenges; you should have a 2:1 or better in a physical science with a strong working knowledge of computer code. It would be beneficial to have an appreciation of optics and chemistry, but full training will be provided.

What is Imagine
Our goal, in Imagine, is not to do more of the same, but to do something very different. We bring together several fundamentally different but complementary advanced imaging techniques. But Imagine is about more than revolutionary technologies – we apply these techniques to solve global issues in medicine, biology and healthcare. By combining and harnessing key advances in microscopy we can delve deeper into the detailed architecture and cellular interactions of biological systems.

Funding Notes

This is a full UK EPSRC Ph.D for 3.5 years, including fee and stipend. Eligible candidates must have been resident in the UK for the last 3 years.

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