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“My goal is to gain new insights into the details of how human cells work to repair the damage that occurs in our DNA. Because the better we understand the DNA repair system, the better we will be able to understand a number of diseases. And this, in turn, will increase the chances of developing novel therapies targeting those diseases,” says Pablo Alcon, structural biologist and postdoctoral fellow at The Laboratory of Molecular Biology (LMB) in Cambridge.

Alcon, age 38, is one of the five exceptionally talented early-career researchers to receive the 2024 Lundbeck Foundation Fellowship worth a total of DKK 10 million (EUR 1.3). The fellowship grant, which will be disbursed over the next five years, enables Alcon to set up his own research team at the Department of Molecular Biology and Genetics at Aarhus University.

Damage to the DNA that makes up our hereditary material may be caused by various stresses and strains, including the ‘wear and tear’ of ageing. The older we become, the greater the damage to our DNA under the effects of normal metabolic processes, in the same way that our clothing, shoes and cars inevitably wear out from ordinary use. But the damage can also be caused by external agents such as chemicals or radiation, Alcon explains:

“Throughout evolution, our cells have developed a complex system involving hundreds of proteins, which at the molecular level is capable of detecting and repairing DNA damage. However, the system is unable to catch and repair all the DNA damage that arises for various reasons along the way. Because of this, some of the damage builds up, and aside from ordinary ageing processes, this build-up is associated with a number of serious diseases such as various forms of cancer and certain neurodegenerative diseases.”

Alcon’s research team at Aarhus University will be conducting detailed studies of proteins specialised in DNA damage detection and repair. The studies will be conducted with the aid of cryogenic electron microscopy (cryo-EM). This technique, awarded a Nobel Prize in 2017, makes it possible to obtain a 3D image of biological structures at molecular level when studying specimens at extremely low temperatures.

“With the aid of cryo-EM, we will be looking at proteins to understand their mechanisms for detecting or repairing DNA damage,” explains Alcon. He has previously conducted research in Denmark and holds a PhD from the University of Copenhagen.

It is well-established scientifically that mutations in the proteins responsible for DNA repair can cause serious diseases, including cancer. Alcon has previously been involved in demonstrating this type of link. A few years ago, he was part of a research team which presented evidence for the molecular architecture behind a protein complex that plays a key role in Fanconi anaemia (FA), a rare hereditary blood disorder that typically involves physical deformities and increased cancer risk.

About the 2024 LF Fellows: 

Five rising scientists receive grants worth millions to lead their own research projects