Charting the blueprints for future disease treatments through cell self-organization
Prize-winning ERC grantees Anna Akhmanova and Marileen Dogterom combined cutting-edge research in the fields of biophysics and biology to achieve a better understanding of how cells self-organize. Their findings could have far-reaching implications for our ability to manipulate cells and treat diseases such as cancer.
In recent years, researchers have made good progress in understanding the individual components of the cytoskeleton, the network of protein filaments that makes up a key part of the structure of our cells. However, it is still unclear as to how exactly these complex cellular systems are built from the bottom up. If this could be understood, it could open a new chapter in the manipulation of cells, regenerative medicine, and the treatment of diseases like cancer.
“Think of how a building is made up of different parts, like bricks and glass,” explains Anna Akhmanova, Professor of Cell Biology at Utrecht University in the Netherlands. “A cell is similar. However, while there is an architect to design a building, there are no plans drawn up for cells. Understanding how this process of self-organization works is the grand challenge of modern biology.”
Backed by an ERC Synergy grant, which is designed to foster collaboration, Akhmanova and Marileen Dogterom, Chair of the Department of Bio-Nanoscience at Technical University Delft in the Netherlands, set out to pool their expertise to tackle the issue together. In practice, this has meant looking at the physical and chemical properties of cell structure, as well as more globally at how cell biology translates into functionality.
Together, the grantees focused their work on microtubules – the thin, long tubes found in every cell that form part of the cytoskeleton. Microtubules separate chromosomes during cell division and help to control cell shape. “We knew that microtubules help cells to organize themselves, just like you need streets to organize and run a city,” says Akhmanova.
The grant also enabled the two researchers to bring other collaborators with specific expertise on board. They then set about trying to reconstitute in vitro these complex microtubule networks, to work out how these systems are built. The success of this approach enabled Akhmanova and Dogterom to then compare “what we had built in vitro with what actually happens in cells in vivo”.
Critically, the project also looked at specific behaviours such as microtubule growth, as well as processes relevant to how cancer cells move around the body. “We were able to show that the ability of cancer cells to grow long microtubules is important to their movement,” says Akhmanova. “This was one of the ways we were able to connect theory with scientific evidence.”
Understanding cell behavior
This transformative research had not been done before on such a large scale. The ecosystem of ERC support also enabled Akhmanova and Dogterom to pioneer new techniques, such as the use of light, to try and control cell behaviour. “What is interesting about the cytoskeleton is that if the same building blocks are organized differently, you end up with a different function,” explains Dogterom. “So how can you change cell behaviour? This is the dot on the horizon where we want to get to.”
Their research has already helped to advance the building of complex biological systems outside the cell, an area of research in which Europe is becoming a leader. The project has helped to strengthen the European Synthetic Cell Initiative, which brings together researchers dedicated to better understanding cellular behaviour by reconstituting cellular functions in vitro.
Significantly, the pair won the Netherlands’ prestigious NWO Spinoza Award – the highest award in Dutch science – in 2018 for their outstanding and groundbreaking work. Both have committed to using the award funds to continue their collaborative work. “The beauty of this ERC Synergy grant is that it enabled us to really tackle big issues,” says Dogterom. “We won’t be stopping here.”
Interview with Anna Akhmanova:
About the researchers
Anna Akhmanova is Professor of Cell Biology at Utrecht University in the Netherlands. After studying biology, cell biology, and biochemistry at Moscow State University, Akhmanova completed her PhD in the Netherlands at Radboud University Nijmegen (RU). In 2011, she took up her post leading the Division of Cell Biology at Utrecht University.
Marileen Dogterom is Professor and Department Chair of Bionanoscience within the Kavli Institute of Nanoscience at Delft University of Technology in the Netherlands. In 1994, Dogterom completed her PhD at the University of Paris-Sud, France, having conducted part of the research at Princeton University, USA. In 2014, she took up her current post at the Kavli Institute of Nanoscience.
This article was first published here by the European Research Council on May 6, as part of an interview series to celebrate ERC’s 10,000th grantee. Together, the two scientists were awarded an ERC Synergy grant in 2013.