In order to encourage outstanding doctoral dissertations, the Münchner Bank, the Verein der Freunde und Förderer (VdFF) and the Helmholtz Graduate School Environmental Health (HELENA) again awarded three doctoral prizes in autumn. Each is endowed with 1,500 Euros. Ilona Kammerl received one of the awards. In an interview, we discussed her doctoral dissertation.
Mrs. Kammerl, please describe your project.
A constant protein turnover takes place in every cell. The immunoproteasome plays a significant role in protein degradation in immune cells, while the so-called standard proteasome takes over this role in non-immune cells. The degradation products of proteins are used to recycle amino acids, and are also presented to the immune system at the cell surface by means of MHC I molecules. In the form of CD8+ T cells, the immune system can discriminate if the protein fragments come from the body's own protein or from extraneous protein, such as from viruses.
During a viral infection, interferon-γ also induces immunoproteasome in non-immune cells, which leads to a higher processing rate and more efficient presentation of intracellular protein fragments. As a result, immunoproteasomes help to improve the CD8+ T cell response and combat viral infections because it enables recognition and destruction of infected cells.
As a part of my doctoral work, we were able to show that cigarette smoke, which is known to be the primary risk factor for Chronic Obstructive Pulmonary Disease (COPD), inhibits the activity of both standard proteasomes and immunoproteasomes. This could lead to increased susceptibility to viral infections in smokers and COPD patients, because infected cells are not as easily recognized as such.
We were furthermore able to show that proteasome activity is significantly reduced in lung tissue of patients with end-stage COPD and the expression of immunoproteasomes in immune cells in the lung is already reduced in early COPD stages. The frequency and severity of viral infections are important factors for the prognosis of COPD patients. The restoration of an efficient immune response, which also includes immunoproteasome function, would therefore be desirable.
How did you hear about the Helmholtz Zentrum München?
When I was working on my master’s degree in Molecular Medicine at the University of Ulm, I looked into various doctoral programmes. The Comprehensive Pneumology Center (CPC), with its integrated “Lung Biology and Disease” graduate school, greatly appealed to me right from the start because it combines clinical research with basic research. The application phase was very professional and I found it very easy to choose the CPC and the topic for my doctoral work.
How important was the supervision you received during your doctoral work?
I received very good supervision throughout my entire work on my thesis. At the beginning, our results contradicted our original hypothesis and we were forced to rethink things after the first six months; nevertheless, there was always constructive and sound scientific discussion with my direct adviser, Silke Meiners. This also made it necessary to replace a member of my Thesis Committee in order to change the focus of the topic. I have fond memories of meeting with my Thesis Committee because it was a good opportunity to summarize the project's status and take a critical look at it.
How important were the offers of the HELENA Graduate School and the Lung Research School?
I am very grateful to HELENA for enabling me to attend my first conference in the USA. The offer in Großhadern was very diverse, and top-level researchers from Germany and abroad were invited to give lectures. Although it took up a lot of time, it is nevertheless a wonderful opportunity to acquire soft skills that go beyond the purely scientific training. I would not have wanted to miss that.
What are your plans for the future?
I am currently employed as a Postdoc and am continuing to work on immunoproteasome in lung diseases, and I am very happy about that. I would like to stay in research and have already successfully obtained a grant for third-party funding, and I hope that more will follow soon.
Mrs. Kammerl, thank you very much!
Dr. Ilona Kammerl: Proteasome and immunoproteasome function in cigarette smoke-mediated chronic lung disease https://edoc.ub.uni-muenchen.de/19128/