Insights into the mechanisms behind metastasis
“The role of NFR2 in melanoma progression” is the title of a research project at IMC University of Applied Sciences Krems which is investigating metastatic skin melanomas that have developed resistance mechanisms. The emphasis is on the protective system which is induced by the transcription factor NRF2 and is often highly upregulated in cancer cells. This enables such cells to handle the by-products of their increased energy metabolism more effectively, which can cause them to become resistant to treatment. The efficacy of cancer therapies could be enhanced by using medication to influence this protective system. One of the core techniques deployed in this approach is the analysis of proteins using mass spectrometry.
The project is funded by Niederösterreichische Forschungs- und Bildungsges.m.b.H. (NFB) and the research is being carried out in collaboration with the Medical University of Vienna (MedUni Vienna) and Karl Landsteiner University of Health Sciences.
What is the focus of your current research project?
The project is part of the Lower Austrian provincial government’s Life Science Call, and it’s centred on the subject of oxidative stress in melanoma treatment and progression. The transcription factor NRF2 is the most important regulator of the cellular response to increased oxidative stress. We are investigating it as a potential target for synergistic treatment using existing therapies, and as a possible driver of the formation of malignant tumours. Here at IMC Krems we’re using a special technique – mass spectrometry for protein analysis, or what we call proteomics, which is the biochemical analysis of cell proteins.
How is mass spectrometry used in proteomics?
Mass spectrometry-based proteomics is a complex and very equipment-intensive approach which enables us to identify and quantify numerous proteins simultaneously from very small samples by determining the mass of biomolecules and creating highly specific peptide fraction spectrums.
Where can this technique be applied?
One of the key strengths of analysing proteins using mass spectrometry is that it can be adapted fairly easily to different sample types and questions. It also supports very detailed analysis. For example, it enables us to identify and quantify thousands of proteins from cell cultures at the same time. Established proteome analysis methods open up a host of possibilities for investigating other questions. We’re working with our project partners on subjects such as the characterisation of microvesicles and the processes involved in multiple myeloma. Some great follow-up projects are taking shape and we’re coming up with new ideas for projects all the time.
What makes this project so unique?
The systems biology approach and proteome screening following modulation of NRF2 in the test systems has given us an insight into the previously unknown effects of the NRF2-controlled process, which appear at the protein level. Characterising the NRF2-controlled defence mechanism will help us to gain a better understanding of the effectiveness or otherwise of treatments and combined treatments, and insights into possible influences on tumour development.
Can you give us a picture of what your research involves?
There are many dimensions to it. Of course, it’s partly conventional lab work using pipettes and Eppendorf tubes to process samples and prepare them for analysis. On the other hand, measuring and evaluating the samples involves operating high-tech equipment, as well as hours and hours of work with control and assessment programs.
How did you come up with the idea for your PhD?
I’ve always been fascinated by the complex biological functions that support life, and that was the reason why I decided to do my PhD at MedUni Vienna. I gained a lot of experience in cancer research during my practical training semester there, which was part of my master degree at IMC Krems. When these two institutions launched a joint project on this topic, I knew straight away that I would like to continue working on it for my PhD.
Where do you see yourself in a few years’ time?
Life sciences, and its research arm in particular, is constantly evolving, which translates into lots of flexibility. As long as there are interesting questions that need to be examined, and the demand is there, I would be happy to apply the expertise I’ve gained to investigate them. The skills I’ve built up in connection with proteomics and mass spectrometry during my PhD and subsequent projects are in demand in academia and in the private sector, so I’m optimistic looking ahead to the future.
What do you find so exciting about your research at IMC Krems?
Research is varied, engrossing and calls for a degree of creativity. And I’m an inquisitive sort of person, so it’s exactly the right place for me. What’s more, teaching and research are closely interlinked at IMC Krems. Writing articles on practicals in the lab, or discussing current research projects with students make a nice change and I find them particularly inspiring.
About Hans Peter Weitzenböck
Hans Peter Weitzenböck, MSc. (28) completed the Medical and Pharmaceutical Biotechnology bachelor and master programmes at IMC Krems, obtaining his master certificate in 2016. Since then, he has been working on research projects in the Department of Life Sciences. He is currently working towards a PhD at the Medical University of Vienna. His PhD project – a partnership between MedUni Vienna and IMC Krems – has enabled him to continue working in the fields of cancer research and proteomics, as well as applying and expanding his expertise.