Joyce is building a village in a petri dish to comprehend diversity

Prof. Joyce van Meurs beams when she discusses her Health & Technology research project. She is one of the leads of a team that is building what she calls a village-in-a-petri-dish. ‘Whoever I talk to about it is enthusiastic, from cell biologists to neuroscientists or data analysts. Scientists from all walks of life think: wow, there is a lot we can do with this.’

More on the applications later, first on the village itself. The inhabitants of the village are stem cells. More specifically, they are so-called induced pluripotent stem cells (iPSC). These stem cells are made in the laboratory from body cells, such as skin or blood cells. In a petri dish, iPSC can grow into all kinds of body cells: from muscle cells to cartilage cells and from liver cells to brain cells.

‘With these cells, we can control everything’

The ability of these stem cells to grow into body cells has revolutionized research into the origin of diseases. ‘We used to depend on tissue available at the hospital, for example, from a biopsy or surgery. But that’s often already diseased tissue, and it is unclear what happened to it. With these iPS cells, we can control everything. We can let them grow under controlled conditions, from stem cells to healthy or diseased body cells. And we can study how they respond to stimuli, such as inflammation.’

Innovative

It is an approach that cell biologists have known about for ages. They use human cells in a petri dish to study disease. These are called ‘cell models’. Often, the cells in such a model come from one person. The village-in-a-petri-dish project by Joyce and colleagues is also a model, but what’s innovative about it is that cells from multiple individuals are in the same petri dish together. Like people in a village; that’s where the name village culture comes from. The combination of various individuals makes the village a model for a population, including all the mutual differences.

There are a lot of differences between people; for example, think of something visible like body height and eye colour. And even in terms of more complex traits, such as our risk of disease or how our bodies respond to treatment, we are all different. According to Joyce, those differences are mainly due to the unique genetic code we all carry in each of our cells. ‘Genetic studies with millions of people show that certain genes are involved in disease. In this project, we link those large-scale genetics to cell biology. To better understand how differences in genetics and environment affect disease and health.’

So, what are the practical implications of such a project? Joyce explains: ‘We purchased iPS cells of a hundred people from a biobank in England. People like you and me. We know the complete genetic code of all these people. We then put the stem cells together in a culture dish. We let them grow, all under the same conditions, into the different body cells we are interested in.’ After doing so, Joyce and her colleagues can simultaneously expose all the cells in the village to a stimulus of their choice. That might be an inflammatory agent to mimic obesity, for example, or UV radiation to mimic the sun.

A hundred times

Joyce explains that the village-in-a-petri dish approach has several advantages. ‘We suppress noise by doing the same procedure on cells from a hundred individuals simultaneously. If you were to do the same experiment for each individual separately, you would have to do the same procedure a hundred times. That increases the chance of tiny errors and, thus, variations in the result. Moreover, it costs more time and money.’

The team uses the latest technology to measure each cell’s response to the stimulus. ‘Because we know the DNA profile of all the different cells, we can ultimately say: this cell belongs to that person. We link individual genetic variations to what is happening in the cell at a biological and molecular level.’

Collaboration

The collaboration with TU Delft is useful, particularly in the measurements and their analysis. ‘They understand mathematical and artificial intelligence techniques, such as pattern recognition, game theory, machine learning and deep learning. That is very useful for when we have to analyze the data.’

‘I notice a certain enthusiasm every time we are together’

All this new knowledge excites Joyce. ‘The colleagues from TU Delft add another dimension. That is super interesting. I am, for example, not at home in game theory. I like the fact that everyone in the project speaks a different language. I notice a certain enthusiasm every time we are together. Everyone has a different perspective. That excites me.’

Infinite applications

Because the village-in-a petri-dish has an almost infinite list of potential applications, the project receives a lot of interest and enthusiasm from other scientists. Joyce and colleagues are starting their research on fibrosis and DNA damage in Rotterdam. Logical choices, Joyce explains. ‘Fibrosis is actually scar tissue. It plays a role in many diseases, such as lung disease, liver disease and osteoarthritis. But we don’t know very much about it yet. We do have an enormous amount of expertise in DNA repair at Erasmus MC. We know a lot about its’ biology, so it makes sense to start with that. DNA repair is important for many patients: it plays a role in cancer and ageing.’

But that is not all: in the future, the model could also be used to predict in whom a treatment will succeed or even to screen new drugs. Experts from Erasmus University Rotterdam have joined the project to make the right choices about which applications are relevant and cost-effective. They determine at an early stage whether potential applications of the cell models make sense.

Joyce: ‘It is, in principle, multi-applicable. We are now in the phase of building the model. But after that, it becomes interesting for others to start using it. My goal is that at the end of this project, we have a model that fellow scientists can further build on.’