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.