Karolin Voßgröne - ESR 1

Name: Karolin Voßgröne

Nationality: German

Main Host Institution: Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Denmark

Academic Background: Bachelors in Biological Sciences, University of Osnabrück, Masters in Molecular Medicine, University of Göttingen

Project Title: Investigating new synthetic lethal interactions and new tumor suppressor candidates in breast cancer

Layman´s description of my project

Project Background: According to the world health organization (WHO), breast cancer belonged to the 5th most lethal cancers in 2015. Irradiation and chemotherapy are applied in breast cancer treatment, but these usually not only affect cancer cells, but also healthy cells resulting in side effects. During the last decades researchers have found more targeted strategies to treat cancer, including breast cancer, in order to reduce side effects. Cancer develops due to acquired cancer mutations, which are changes in the genome of cells. They allow cancer cells to proliferate unlimited, whereas healthy cells do not have the ability to do so and allow the application of targeted therapies.

With more than 50 % of affected cancers, including breast cancer, p53 is the most abundantly mutated protein. Its function has been described as the “guardian of the genome”, since it is involved in the repair of DNA and induced cell death if the damage is irreparable. When p53 is mutated, the cancer cells loose the protective function of this protein and the cell will continue to proliferate with lesions in the genome, maybe even more contributing to tumor growth, but also making these cells more sensitive to inhibition of other repair pathways compared to healthy cells. Targeting these would lead to specific death of cancer cells since cells can only survive a certain amount of DNA damage, a concept known as synthetic lethality.

Another family of proteins that can harm the DNA are nucleases, which act like scissors on the genome. Nucleases are cutting DNA in order to remove lesions and make the DNA accessible for repair proteins. On the other side, these proteins are activated in induced cell death. Therefore, their function needs to be tightly controlled in order to ensure repair of DNA lesions but to prevent unwanted cell death.

Project Aim:  We aim in identifying synthetic lethal interactions between p53 and nucleases in order to find new targets or treatment strategies for breast cancer patients.

Expected Outcome:  High throughput screening for synthetic lethal interactions enables us to test all nucleases within the human cell for synthetic lethality in p53 negative cancer cells. Following validation of the screening results, the most relevant candidates will be further investigated to understand their function.

Contact:  Karolin Voßgröne