Being able to image the microcirculation is a key technology in the determination of vascular physiology. My research focuses on developing 3D light and electron microscopy techniques in order to better describe the microcirculation.
2017-2020 Medical Research Council - New Investigator Research Grant
Variation in Glycocalyx Structure in Diabetes
Diabetic Retinopathy and Diabetic Nephropathy cause blindness and kidney failure associated by leaky blood vessels. The proposed research is focused on the endothelial glycocalyx. This is a specialised layer that covers blood vessel walls and acts as a molecular filter so the correct molecules transverse blood vessel walls. In normal physiology this filter is a layer of fibres spaced regularly at 20nm apart. The systemic disruption of this layer is well established in diabetes but what the disruption is, and what mechanism causes it, is totally unknown.
The overarching aim is to determine the basis of the filtration functionality by understanding the glycocalyx fibre organisational structure and how this is changed in diabetic model systems. The proposal will use state-of-the-art three dimensional, structural, and analytical electron microscopy techniques to determine structure whilst systematically altering the constituent components and functionality (permeability) of the glycocalyx.
PDRA: Dr Claire Allen
Main Collaborators: Prof. Dave Bates, Dr Cathy Merry, Dr Roland Fleck, Prof. Klaus Qvortrup.
2017 Research Priority Area - Rapid Response
Rapid Implementation of Novel Imaging
A project to pair developmental bio-photonics instruments in Electrical Engineering (Dr Amanda Wright, Dr Chung See) optimised for technique development with biological-user friendly counterparts in the Division of Cancer and Stem Cells (Dr Cathy Merry, Dr Alan McIntyre). We are using a novel 3D optical microscopy technique as an exemplar for efficiently translating method development to medical research.
2017 Research Priority Area - Regenerative Medicine and Stem Cells
One of the goals of this research priority area is to pump prime novel research to help drive the next generation of scientists. This award was to bring together physical sciences microscopy and medical science research techniques to help fast-track novel photonics towards clinical questions. The particular example we will use is to combine dynamic optical (Dr Amanda Wright) and electron ultrastuctural lipid measurement techniques with oxygen variation (Dr Victoria James and Dr Alan McIntyre).
2016-2017 Facility for Environmental Nanoscience Characterisation and Analysis
Determining Dynamic Nanoparticle Uptake On Subcellular Scale Using Correlative light Electron Microscopy
Environmentally relevant nanoparticles (e.g. Silver used in industrial processes) have similar issues to medical nanoparticles used in drug delivery when it comes to detecting where in tissue they have gone. This project is to combine the knowledge of the medical field with the environmental field to create a combined workflow within the FENAC facility.
Main Collaborators: FENAC, Prof. Paul Verkade, Dr Lorna Hodgson and Mrs Judith Mantell
2015-2017 British Heart Foundation
Novel nanosensors for real time determination of shear stress experienced by the endothelial surface layer
The wall shear stress is the force of a fluid on a surface, and in blood vessels this force changes how the walls of the blood vessels behave. In diseases such as cancer, atherosclerosis and diabetes changes in the physical and biochemical behaviour are linked to the wall shear stress yet it cannot be measured accurately.
Myself, with collaborators from several universities, have designed a semi-rigid bio-synthetic nanoparticle that is shaped as a piece of string. It is 900nm long but only 7nm wide. We attach this to any surface using a surface dependent molecule and image how the particle reacts to fluids. The current work is to alter the design the particle to work in physiological environments.
Main Collaborators: Prof. Tim Dafforn, Prof. Dave Bates, Dr Dave Smith
2015-2017 Bizkaia Talent Fellowship - (University of the Basque Country)
Regulation of Nuclear Envelope Architecture: A Hallmark in Ageing
The internal membranes around the nucleus extend out into the whole cell. As tissues age the processes within cells dividing degrades. The membranes are made of a concoction of lipid bilayers that have different abilities to curve. This project aims to determine the curvature of lipids, hence their make-up and function, using a combination of 3D Correlative Light Electron Microscopy techniques.
Main Collaborators: Prof. Banafshe Larijani, Dr Lucy Collinson, Prof. Paul Verkade, Prof. Dominic Poccia
Funded PhD Studentships Available
Biological Mathematics (with Dr Reuben O'Dea): Blood Vessel Permeability
MRC IMPACT DTP (Recruiting NOW!!!):
The Role of the Glycocalyx Structure in Vascular Permeability
Medicine Legacy Studentship (Recruiting NOW!!!):
The Structure of Endothelial Glycoclayx Components Using Cryo Electron Tomography
+ Other possibilities for UK,EU and overseas