WHAT do you call a fish without an eye? Clue: the answer isn’t “fsh”. At least, not in the darkest depths of the UCL Anatomy building, where the Zebrafish Research groups keep many thousands of these tiny striped fish. Aside from fish carrying mutations that lead to their offspring missing part of their eyes or their brains, there are transparent fish as well as the somewhat more attractive glow-in-the-dark fish. Anxious to find out what could possibly be the scientific value of fluorescent fish, I attended an OpenLabs session hosted by Dr Matina Tsalavouta in Steve Wilson’s Research Group in conjunction with the Synthetic Biology Society.
Prof Wilson’s research group is composed of three subgroups, one studying brain asymmetry, one studying eye development, and one developing an atlas of the zebrafish brain. Zebrafish have been a big hit with researchers for several reasons: they’re small, hardy, and rapidly reach maturity. They also have the amazing ability to regrow their own heart, fins, and skin, which makes them of particular interest to stem cell and regeneration projects. Zebrafish are extremely easy to breed, as their breeding behaviour is regulated by exposure to light, meaning you simply need to switch off the lights for a few hours, and when the lights come on again you get a baby zebrafish. There is a slight hitch, however – zebrafish will eat their own eggs if left alone with them, so they have to be kept in special breeding boxes which keep them separated from their eggs.
But how do you make fish glow in the dark? The green fluorescent protein (GFP) gene – termed a “glow in the dark gene” – can literally highlight areas of interest within the fish. The gene construct can be injected into the fish embryo at the single-cell stage. As the embryo grows, the GFP construct becomes incorporated into their genome, and as a result you get a fluorescent fish. Researchers are then able to take high-quality and often strangely beautiful images of, for example, the fish brain. Transgenic fish with other types of fluorescent protein can be used to visualise brain activity, allowing scientists to see when and where a set of neurons is active under different experimental conditions. They can also track which parts of the brain are activated in response to certain stimuli when the fish are developing normally, or when certain genes do not function or tissues are compromised.
The use of GFP is incredibly versatile; it can also be inserted into individual brain cells, allowing researchers to detect the connectivity of a single neuron within the brain. Other cell types can also be infiltrated such as macrophages, a special type of white blood cells involved in the immune response. Dr Tsalavouta showed us a video, taken in another lab, of a single glowing macrophage rushing to the site of injury in a zebrafish body. Whilst this may look like something from an avant-garde film, this kind of imaging is invaluable to researchers, providing a clarity which would not be possible without the use of fluorescent proteins. And it turns out zebrafish aren’t just popular at UCL – they are used in labs across the world, including those of the British Heart Foundation, which last year began a project investigating the zebrafish’s ability to regrow its own tissue from stem cells.
Given that zebrafish have been used as a model organism for over 30 years, it is perhaps surprising that we actually know relatively little about the detailed neuroanatomy, the connectivity and circuitry formation of their brain. Dr Tsalavouta told us about the work of another group within Prof Wilson’s laboratory which is developing an online, high-resolution atlas of the developing zebrafish brain, which aims to serve as a tool for research in labs across the world. Other recent zebrafish studies at UCL have revealed how our eyes take shape, and how the tissues of the eye regulate their growth, helping us to better understand the mechanisms behind tumour growth.
As an undergraduate it’s all too easy to forget that UCL is a world-leading research centre, and I came away from the hour-long OpenLab session happy to have gained some insight into the world of cutting-edge research that takes place under our very noses.
Synthetic Biology Society would like to thank Dr Steve Wilson and Dr Matina Tsalavouta for making this OpenLabs event possible. To find out more about the next OpenLabs series, head to synbiosoc.org.