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
Hi,
My name is Karolin and I am 28 years old. I am German but moved for my studies to Copenhagen, Denmark. Below is a description about my PhD project.
Superpowers are weaknesses of cancer cells
Our body consists of many cells and they are constantly renewing themselves. Every time a cell divides, our genetic information needs to be copied precisely to prevent an accumulation of defects that could cause cancer and other diseases. Two protein groups are very important for copying the genetic information as well as repairing defects. One group is helicases, which - like a zipper - unlocks the genetic information within the cell. This is required to give copy- and repair machineries access to the genetic information. The second group is called nucleases. Often, they are part of repair machineries, which - like a pair of scissors - cut the DNA at damaged sites to remove defects.
Cancer cells have changes in the genetic information compared to healthy cells, which we call mutations. These mutations can give a cancer cell superpowers. However, these superpowers are also a weak point. My project aims firstly to identify scissors and zippers that maintain the genetic information and secondly to identify weak spots of cells with deregulated scissors or zippers. During this project, I have identified new zippers that maintain the genetic information. The selected zippers are deregulated in cancer cells, which means they could contribute to tumor development or progression. Currently, I am working on understanding how these zippers maintain the genetic information. Simultaneously, I am testing which weaknesses cells with these deregulated zippers have. Therefore, I will treat cells with deregulated zipper with different drugs. For this, a big screening approach will be used, which allows us to test hundreds of drugs.
Ideally, the cells with deregulated zippers are more sensitive to at least one drug. Accordingly, the drug will specifically kill cancer cells with the deregulated zipper and can therefore improve cancer treatment.