Fredrik Westerlund

ERC-grant for next generation DNA-repair analysis

How is damaged DNA repaired, and why are there sometimes errors in the process? Fredrik Westerlund, Professor in Chemical Biology, receives the prestigious ERC Consolidator grant to investigate these mechanisms using nanotechnology tools.

Fredrik Westerlund at the Department of Biology and Biological Engineering is one of two researchers at Chalmers to receive the prestigious research grant ERC Consolidator for his project “Next Generation Nanofluidics for Single Molecule Analysis of DNA Repair Dynamics” (nanoDNArepair). The ERC grants are financed by the European Research Council and are awarded yearly to the most eminent researchers in Europe. Fredrik Westerlund is awarded two million Euros for a five-year project.

Research with great relevance
“It makes me very happy to receive this grant. This is proof of my research having great relevance and that it can make a difference. This will also open many doors for collaborations, which can make the research and results even better,” says Fredrik Westerlund. 

Interactions between DNA and proteins
The project is divided into two parts, one part is method development for investigating interactions between DNA and proteins, focusing on the ends of the DNA.

“We want to investigate how proteins and DNA interact, and focus on how just one protein, or a small group of proteins, interact with single DNA-molecules. This is how the processes function in our cells,” says Fredrik Westerlund.

New method based on nanofluidics
The new method is based on nanofluidics where single DNA-molecules are studied in nanochannels, thin glass tubes, using fluorescence microscopy. In the nanochannels the DNA-molecules are stretched out, in contrast to in free solution where they are wrapped like a ball of yarn.

“When using other methods for single DNA molecule analysis, the ends need to be attached to something. That makes it impossible to study what happens in these areas. The ends are very relevant to study, especially for DNA repair analysis. In our nanochannels the DNA is suspended free in solution and the whole molecule can be examined. Now we want to find ways to add proteins to the DNA in the nanochannels in real time to characterise how they interact with the DNA,” says Fredrik Westerlund.

Focus on mechanisms of DNA-repair
In the biochemical part of the project focus lies on the mechanisms of the repair of broken DNA. The DNA in our cells can break, which is a naturally occurring process, but also happens when treating cells with, for example, radiation or chemotherapy. In all cells there are therefore protein systems that repair DNA, but things can go wrong in the process.

DNA that has not been correctly repaired can result in genetic information being lost or modified, which can lead to that the cell will misfunction. This could lead to cells dying, but more importantly, two mismatched DNA ends linked can result in wrong genetic information, which in turn can be an underlying reason for disease, for example cancer.

Project can contribute to drug development
The focus of Fredrik Westerlund’s research will be one of two main mechanisms for repairing DNA-breaks, so called Non-Homologous End-Joining (NHEJ). During this process a fracture in the DNA is repaired without having a template, and any loose ends can be joined. This is a common repair process in all life forms, but it can go wrong.

Besides contributing to the general knowledge about these mechanisms the project nanoDNArepair can contribute to drug development in the long run, for example better treatment of cancer or bacterial infections.

Turn off NHEJ in tumor cells
“Even though this project is fundamental research the results can eventually be applied. Cytostatic drugs and radiation therapy aim to damage DNA in tumor cells. NHEJ continuously fights back and repairs the damaged DNA in the tumor cells. If we could turn off NHEJ in the tumor cells the effect could be that less drugs or radiation is needed, which would give less side effects in other cells,” says Fredrik Westerlund.

Target NHEJ in bacteria
In bacteria new antibiotics could target the NHEJ-system. For example, studies have shown that latent tuberculosis is depending on a functioning NHEJ-system to rest in the body over a long period of time.

Show the breadth of nanofluidics
“It is very inspiring to lead a project of this magnitude, based on both development of new techniques and then using these techniques to answer important questions in biophysics and biochemistry. We are one of few groups in the world that use nanofluidics for this purpose, so I am happy that the ERC sees the same potential of the method as I do. An important part of this project for me will be to show the breadth of the method for application in other research areas than DNA repair,” says Fredrik Westerlund.

Facts: Nanofluidics
  • Nanofluidics is a research field that is made possible by the development of methods and machines for manufacturing of very small items. These were originally intended for fabricating tiny computer transistors but have now also found use in completely different fields of research. 
  • In the bio-nanofluidics field channels of ~100nm in height and width are fabricated, where bio-molecules can be “trapped”. Large DNA-molecules are forced to stretch in order to accommodate to the small volume.
  • The method is used widely in the scientific community, all the way from genetics to fundamental issues addressed in nanoDNArepair.
Besides Fredrik Westerlund, Åsa Haglund Professor at the Photonics Laboratory at MC2, managed to get an ERC Consolidator Grant in this round.

Text: Susanne Nilsson Lindh
Photo: Johan Bodell

Published: Tue 10 Dec 2019.