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Next Generation High-Speed Atomic Force Microscopy in the Wolfson Imaging Facility


   Faculty of Engineering and Physical Sciences

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  Dr G Heath  No more applications being accepted  Competition Funded PhD Project (UK Students Only)

About the Project

To better understand diseases and to develop new treatment options, we need to understand very fast biological processes occurring at single molecule level. However, obtaining sufficient spatial and temporal resolution is a major challenge, where current techniques are limited. Here you will focus on developing high-resolution high-speed atomic force microscopy (HS-AFM) in the newly established Wolfson Imaging Facility to image and decipher biological phenomena which have been previously undetectable. Depending on your scientific interests your project will focus on using HS-AFM to tackle one of the following biomedical challenges:

1. Dynamics of Amyloid Fibrils (Co-supervised by Sheena Radford). The self-assembly of insoluble fibrils is involved in the laying down and storage of long-term memories but also associated with an array of human disorders, including type II diabetes, Alzheimer's disease and Parkinson's disease. HS-AFM will be used to measure amyloid fibril formation kinetics and their interactions with small molecules. 

2. How do Ion Channels Sense Force? (Co-supervised by David Beech and Christos Pliotas) - Mechanosensitive channels are found throughout all forms of life, acting as force sensors for touch, hearing, responses to gravity and osmotic pressure and cardiovascular regulation. You will use HS-AFM to measure conformational dynamics of single mechanosensitive ion channels in response to mechanical stimuli. 

3. Structural Dynamics of the β-barrel Assembly Machinery (Co-supervised by Sheena Radford). Essential for bacterial survival and highly conserved, this protein complex is an attractive target for small molecule peptide and antibody-based antibiotics. HS-AFM will be used to measure single molecule dynamics of the protein complex and resulting lipid bilayer destabilisation. 

4. Clustering Dynamics of Fcγ Receptors (Co-supervised by Jim Robinson and Stephen Evans). Fcγ Receptors play keys roles autoimmune and inflammatory diseases which affect ~5% of the population, cause joint and end-organ damage, physical disability and reduce life expectancy. Using HS-AFM the assembly dynamics of Fcγ receptors will be measured in model membranes of increasing complexity. 

5. Visualization the Life Cycle of Viruses in Action (Co-supervised by John Barr and Juan Fontana). The Bunyavirales order of RNA viruses comprises some of the most serious human pathogens in existence, including 3 listed by WHO. HS-AFM will be used to image native viral proteins undergoing RNA synthesis to understand key stages in viral replication and test potential anti-viral therapies.


Funding Notes

A highly competitive Wolfson Imaging Facility Studentship consisting of the award of fees with a maintenance grant (currently £17,668 in session 2022/23) for 3.5 years. This opportunity is open to UK applicants only.  All candidates will be placed into the Wolfson Imaging Facility Studentship Competition and selection is based on academic merit. Funding has been provided by a generous philanthropic donation by an alumnus of the University of Leeds.

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