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Tackling messy blood vessels to fight cancer

With a Vici grant of 1.5 million euros, Professor of Mathematical biology Roeland Merks will look for ways to fix messy and leaky blood vessels in tumours. His research combines mathematical simulations and lab experiments in a unique way.

Messy and leaky

Cells on the inside of a tumour are poorly perfused. In order to gain nutrients, the tumour cells activate blood vessel growth. This happens in a poorly regulated way, making the blood vessels in tumours twisty, leaky, and malfunctioning. The oxygen supply is consequently irregular. This makes tumour cells less sensitive to chemotherapy and also makes them more aggressive, allowing them to spread faster in the body. With his research, Merks wants to better understand the mechanisms behind messy blood vessels, and discover how you can repair these mechanisms.

Collective behaviour

He was already performing computer simulations in his earlier work. ‘I have described how an individual blood vessel cell behaves by using mathematical models,’ Merks says. ‘From that, we extrapolate the collective behaviour: the formation of a blood vessel. The simulation methods we use are very similar to those for the collective behaviour of birds in bird flights or for people.’ But, he continues, if we want to really understand blood vessel formation, the model needs to be refined. 

Surroundings of the cells

What is it that determines whether a blood vessel is regular or messy? According to Merks, recent indications suggest it has something to do with the surroundings of the cells. This so-called extracellular matrix determines the spatial structure of the cells. The stiffness of this matrix influences whether the cells form a regular or irregular blood vessel. ‘In my model I want to understand how the change in the matrix determines how the collective behaviour of the cells changes. I will get the lab to perform experiments that may not match our model, and I will then try to correct the model. So the mathematical model plays a guiding role in this research.    

Merger of mathematics and biology

Alongside his professorship Merks works at Centrum Wiskunde & Informatica (CWI). ‘This project will take place at the Mathematical Institute (MI), the Institute of Biology Leiden (IBL) and CWI,’ says Merks. ‘What very often happens is that the different specialisations work in separate offices and they grow apart. What makes this project different is that the mathematical and the experimental biologists will sit together in one room. In this way, they will talk to each other on a daily basis, so that they learn to understand each other's perspectives and really work together.'

Five-year goal

Merks says that he wants to achieve two things in these five years. ‘First, I hope to determine in the lab which factors determine the switch between an irregular tumour network and a regular and healthy blood vessel network. I also hope to achieve such a switch in a cell culture and eventually in zebrafish. Secondly, a key aspect of this project is methodology development. I hope that our approach – in which the mathematical model guides the experiments – can become a blueprint for similar interdisciplinary projects in developmental biology.

Merks is a biologist by training and works at the Centrum Wiskunde & Informatica (CWI). He is also a professor at the Mathematical Institute (MI) in Leiden. In 2011, he received a Vidi grant for the mathematical modelling of interactions between cells via the extracellular matrix during blood vessel growth. He will carry out his Vici at the Mathematical Institute (MI), the Institute of Biology Leiden (IBL) and CWI.

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