The microscope helping to find a cure for heart failure
A bespoke 3D microscope could bring insight into the self-healing heart of the zebrafish. Dr Jonathan Taylor, Lecturer in Physics at University of Glasgow, talks to Sarah Kidner.
Biologists may soon have a clearer picture of how the zebrafish is able to repair damage to its heart, moving us another step closer to a cure for heart failure.
Studying the zebrafish is just one of many ways we’re tackling heart failure, a debilitating condition that affects hundreds of thousands of people in the UK. The better we understand how these tiny fish fix their own hearts, the more chance we have of replicating this in humans.
It lets [us] see the full structure of the heart
The zebrafish is transparent, so we’ve been able to get a good idea of how the heart develops by studying it. Now, thanks to a £162,279 BHF grant, Dr Jonathan Taylor and his team at the University of Glasgow are developing a bespoke microscope that will allow us to see the fish’s beating heart in 3D.
“The zebrafish is transparent, which is fantastic for imaging and means we don’t have to harm the fish,” says Dr Taylor. “However, the problem is that it takes a couple of seconds to do a complete 3D image. In the zebrafish, the heart is beating several beats to the second and so the image we end up with is a blur.”
Freezing the motion of the heart
Zebrafish hearts beat so fast that capturing a clear image was a big challenge
To build up a clear 3D image of the zebrafish heart, Dr Taylor is working on a way of using a computer to ‘freeze’ the motion of the heart. “We can get images out as if it were standing still, even though the heart is beating normally,” he says.
To build the 3D image, the team uses a computer that watches the zebrafish’s heart all the time. It analyses the images and can tell precisely what point in the heartbeat you’re at.
The computer takes multiple images at the same precise moment in each heartbeat but of different layers in the heart, and then combines these to create a 3D image. “We can’t just click a mouse and suddenly – bang! – there’s a 3D image,” explains Dr Taylor. “We have to build it up layer by layer, so it’s really important that every single layer is taken at the same point in the heartbeat.”
It’s now possible to create a 3D image, without any blurring, in around 30 seconds, although it’s taken several years of painstaking research to reach this stage.
Selective Plane Illumination Microscopy explained
In order to perform the 3D imaging, the team has used a special kind of optical technology called SPIM, short for Selective Plane Illumination Microscopy.
“I built a microscope with my former colleagues down in Durham,” says Dr Taylor. “It’s custom built, using building blocks like lenses and mirrors, so you wouldn’t recognise it as the sort of microscope you can buy in a shop.”
Dr Taylor hopes his microscope software will help other researchers
Fellow researchers in Edinburgh are using the microscope to study the zebrafish. By combining the SPIM with software developed by Dr Taylor and his team, they’re able to obtain clear 3D images of the zebrafish heart.
SPIM microscopes are becoming commercially available, albeit at a cost of hundreds of thousands of pounds. “If you can afford to buy one, you will get beautiful images of the blood vessels in the tail of the fish or the nerve fibres in the brain of the fish and so on,” says Dr Taylor. “But if you point that at the heart and try to take 3D images, that is when you will just see a mess. Our software is solving that problem.”
Longer term, he hopes his team’s software will integrate with these commercial microscopes, making 3D heart imaging more widely available to biologists. This will mean working in collaboration with the manufacturers in many cases. “One of the end goals for me is that we’ll have something we can just ‘bolt on’ to existing microscopes,” he says.
Helping others to make new discoveries
A team of researchers in Edinburgh is already using Dr Taylor’s techniques to study the zebrafish, enabling them to see things they’ve never seen before. “It lets them see the full structure of the heart,” he says. “If the heart is injured, it’s really hard to know exactly what is going on unless you can see a 3D picture.
“In response to an injury, there will be swelling and inflammation and white blood cells that come along to help with the healing of that injury. One of the basic things we would like to know is: are these white blood cells on the inside or the outside of the heart? If all we see is a big blur, we can’t tell that sort of thing.”
Ultimately, Dr Taylor hopes the work he’s done will help other researchers to make new discoveries. “The sort of thing that I would love to enable them to do is film the growth of the heart, in high resolution and three dimensions, from the very early embryo when it first starts beating to where it grows into a fully functional heart,” he says.
“I will consider the project a complete success if I have enabled biological and biomedical researchers to make discoveries that have only been possible using my microscope design. If they learn new things because of this ability to capture an image of the heart in three dimensions while it is beating normally, then I will be extremely pleased.”
Dr Jonathan Taylor's CV
- Lecturer in Physics at University of Glasgow.
- Awarded a BHF New Horizons grant, in collaboration with Dr Martin Denvir at Edinburgh University, in late 2014. Our New Horizons grants were set up to encourage scientists from outside traditional cardiovascular biology to engage in cardiovascular research and bring new expertise to the field.
- Previously a postdoctoral researcher at Durham University, working on optics, SPIM microscopy and biological imaging.