The Zika virus and the ‘Brain in a Dish’

Author: Stephanie Cumberworth (06/11/2018)

CVR PhD student Stephanie Cumberworth was recently selected as one of the 10 researchers shortlisted for this year's MRC Max Perutz Science Writing Awards. Designed to encourage PhD students to share their research with a wider audience in only 800 words, the awards attract more than 1000 'outstanding' entries each year. Here you can read her entry.

Mosquitoes. You might have encountered these bothersome bloodsuckers whilst enjoying a hard-earned holiday. If you are lucky, a few days of a red itchy bump will be the most you have suffered at the hands of a mosquito bite. However, over 1/3 of the world’s population is at risk of severe infections spread by mosquitos.

One such infection is caused by the Zika virus. The virus rose to media fame in 2016 following an outbreak starting in Brazil which caused devastating, never before seen complications in new-borns. Previously, the Zika virus was thought to cause fever and a rash in 1/5 patients it infects. Now the virus has been linked to some babies being born with abnormally small heads and underdeveloped brains, amongst other neurological symptoms. I am part of a biological super team of neuroscience and virus experts who are investigating the cause of these new symptoms using a ‘brain in a dish’.

Rest assured, the ‘brain in a dish’ is less Frankenstein-ian than its name suggests; nor is it a strange delicacy served up in a bowl like my friends imagined. It isn’t really a brain at all. The ‘brain in a dish’ is actually a collection of different building blocks called cells, interacting with one another similar to how they would in the brain inside a specialised culture dish.

Part of my PhD involves using the ‘Brain in a dish’ to find out how the Zika virus affects these brain cells to try and answer the question: what does the Zika virus do to the brains of infected babies?

To get ‘the brain in a dish’ ready for experiments, we let the cells grow to the developmental stage that is representative of a new-born baby. As each cell type plays a different role in the brain, our first step was to find out which of the cells could be infected with the Zika virus; this might give clues as to what is causing some of the new neurological symptoms.

After infecting the ‘brain in a dish’, I use a chemical to ‘kill’ the virus and preserve the cells so that I can study them closer. Much, much closer in fact.

Next comes my favourite part: illuminating the ‘invisible’.

Individual cells are so small that we can’t see them with the naked eye. Viruses can be 1000x smaller than some cells, making them impossible to see without the right tools. To explore the microscopic landscape of the ‘brain in a dish’ I use specific labels against each cell type and the virus, which fluoresce my chosen colour when excited by a particular wavelength of light. Using a powerful microscope, I can then zoom in to reveal a rainbow of data.

Similar to a game of spot the difference, myself and a team of researchers scoured through images taken with the microscope examining each cell, noting what it was, if it was infected and if it was dying. The only difference being the average game of spot the difference takes minutes, ours took weeks. It wasn’t long before I saw the patterns of cells everywhere I looked.

Our results showed that the main target for Zika virus infection was the oligodendrocyte. To understand the job of an oligodendrocyte, I first need to introduce the neuron. Neurons control every bodily process by sending messages from the brain along ‘wires’, called axons, to distant places in the body. Oligodendrocytes speed up this messaging service by providing a protective coat called the myelin sheath. The myelin sheath acts like the plastic coating around wires, it provides insulation and allows the wire (or axon) to transmit signals more efficiently.

Knowing that the Zika virus infects oligodendrocytes, our attention turned to the protective coat they provide axons – the myelin sheath. We found that infection with the Zika virus actually destroys the myelin sheath in the ‘brain in a dish’. Not only that, we also saw that axons (the wires of the brain) were damaged too. Under the microscope what once appeared as infinite branches of communication, turned into a smattering of debris during infection.

So what does this mean for an infected baby’s brain?

At birth, the axons in a human baby’s brain aren’t all fully covered by the myelin sheath. In fact, this process happens late in pregnancy and occurs all throughout childhood, into early adulthood. If the Zika virus affects the development of the myelin sheath in a new-born, it is possible that more problems might occur later in life. It is my hope to understand more about this myelin loss in the remainder of my PhD, so eventually it may be stopped. For every wire needs an insulating coat.