With a Vici grant of 1.5 million euro, Roeland Merks (CWI and Leiden University) will look for ways to fix messy and leaky blood vessels in tumours. To do so, he 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 get nutrition, the tumour cells activate blood vessel growth. This happens in a poorly regulated way, making the blood vessels in tumours twisty, leaky, and malfunctioning. Because of this the oxygen supply is irregular. This makes tumour cells less sensitive to chemotherapy and 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 recover them.
In his earlier research, he has already started with performing computer simulations. ‘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 says, to really understand blood vessel formation, the model needs to be refined.
Surroundings of the cells
Because what determines if a blood vessel is regular or messy? According to Merks, recent clues state 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. Then I challenge the experimental lab to perform experiments that possibly do not match our model, and I try to correct the model. So the mathematical model plays a guiding role in this research.
Mathematics and biology fusion
Alongside his professorship in Leiden (where he is Professor of Mathematical Biology) 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 happens very often is that the different specializations work in separate offices and they grow apart. The special aspect of this project 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.'
Merks says that he wants to reach 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). Furthermore, he is professor at the Mathematical Institute (MI) in Leiden. In 2011, he received a Vidi grant for the mathematically modelling of interactions between cells via the extracellular matrix during blood vessel growth.