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Nick Gatford
Established in 1975, The Nikon Small World Competition recognises those involved with photography through the light microscope, and is a leading showcase for photomicrographers. Dr Nick Gatford, a Postdoctoral Research Associate and part of the Molecular Neurodegeneration Research Group, won Nikon Small World’s Image of Distinction Award for his image of a network of dopaminergic neurons generated from human stem cells. Nick’s image was featured in National Geographic, alongside other stunning winning entries from over 2,100 submissions, and was recently featured as Biomedical Picture of the Day by the Medical Research Council Laboratory of Medical Sciences.
Hi Nick. Can tell us about yourself and your research?
I am principally a neuroscientist, with a particular interest in using neurons (nerve cells that send and receive signals from in the brain) generated from human stem cells to model neurological disorders. My work currently involves generating a specific sub type of human neuron called dopaminergic neurons – this is the specific type of neuron that deteriorates in Parkinson's disease.
By studying dopaminergic neurons, we may better understand how Parkinson's disease develops in humans and how we may intervene to prevent them from degenerating. The findings from such experiments will someday provide new treatments for Parkinson’s disease in human patients based on extensive development, testing, and validation.
Can you tell me a bit about microscopy?
Microscopy is a broad field of optics which aims to observe small objects that cannot be viewed with the resolution available to the human eye. It has a long history dating back to the 17th century, ranging from Galileo first focusing a telescope on a small object all the way up to Stefan Hell winning the 2014 Nobel prize for the discovery of super-resolution microscopy.
In biology, it lets us see the intricate details of life itself often focusing on the molecular interactions that enable cells to function. I use microscopy to look at exactly how, where, and when proteins of interest interact on a subcellular level using super-resolution microscopy to show such interactions on a nanoscopic scale. Visualising how such interactions happen allows us to identify molecular partners of Parkinson’s disease-associated proteins such as alpha-synuclein, potentially allowing us to interrupt these interactions if they contribute to Parkinson’s disease progression.
Why is microscopy important?
Microscopy is one of the fundamental components of a biologist’s toolkit. Science can become quite abstract for non-scientists; microscopy allows us to show and not just tell people about the exciting breakthroughs we make across the life sciences spectrum.
However, microscopy does not act alone. It works in tandem with other biochemistry techniques to provide combined spatial and temporal information i.e. the where and when of cell biology. I often find microscopy operates best at the crossroads of biology, chemistry, physics, and mathematics, possibly even borrowing principles from the optics of deep space telescopes from time to time for good measure.
Tell me about your winning image. How was it taken?
This image was originally captured during the optimization of a new microscopy technique called correlative light and electron microscopy (CLEM). The goal of CLEM is to spatially connect fluorescent signals from a super-resolution microscope with scattered electron signals from an electron microscope. This allows for observation of the precise subcellular localization of both signals simultaneously, effectively bridging the gap in resolution between these typically separate types of microscopy.
As part of optimizing this technique, multiple stacks of super-resolution images were tiled together to identify specific cells of interest before observation under the electron microscope. Capturing this image required approximately 8000 super-resolution images in the Z axis compiled as a 10x10 tile in the X and Y axes and took an hour to acquire. The acquisition itself was quite ordinary, just bigger and a lot longer than a typical image acquisition.
It was only when I was processing the images after that I realised it had the potential to be something more visually striking with some extra creativity.
What does your image show?
This image shows human dopaminergic neurons generated from human stem cells. Dopaminergic neurons are the main cell type that deteriorates in Parkinson’s disease, partly due to harmful build-up of a protein called alpha-synuclein.
The image consists of multiple tiles stitched together to show a large area of neuronal connections. A colour coded depth-based filter has been applied to highlight the extent to which these neurons are interconnected into a sprawling microscopic network of neuronal interactions.
What does it mean for Parkinson’s Disease?
The cells shown in this image are from stem cells originating from a Parkinson’s disease patient carrying a triplication in the synuclein gene. This genetic mutation results in twice the typical amount of synuclein being present in neurons, which these cells then struggle to dispose of correctly. Ultimately causing a toxic accumulation of synuclein and eventually neurodegeneration that leads to Parkinson’s disease.
Additionally, the dopaminergic subtype of neurons generated here are the first type of neuron to show signs of deterioration as the disease takes effect.
We use these cells to discover new pathways to investigate and interrupt, preventing dopaminergic neurons from degenerating before Parkinson’s disease becomes irreversible. Discovering such pathways guides our development of new drugs to slow their degeneration, ultimately providing new Parkinson’s disease treatments.
How do you feel about winning an Image of Distinction Award in The Nikon Small World competition?
I am consistently amazed by the technical depth, interdisciplinary scope, and artistic variety of photomicrographs produced by the microscopy community as highlighted by the Nikon Small World competition.
To be considered among such beautiful images of our small world and such talented microscopists is an honour.
What’s next for you?
This experiment is one of many that have been a long work in progress for the past three years of my project, so we’re hoping an interesting new publication will be out soon revealing our exciting developments in Parkinson’s disease research. Watch this space!