SCIENCE
Sometimes people ask me, why I decided to study biochemistry. Nostalgically, my mind drifts back to my high school time. Back in high school I enjoyed many things and subjects: I really liked languages and history but also chemistry and biology. My decision was based on intuition. Maybe it was the interesting classes and their content, maybe that moment of looking through the ocular of a microscope for the first time. I looked at a world I had never seen before, invisible to our eyes and therefore so strangely unreal. I did not anticipate the striking complexity of the molecular scale of life back then but I certainly appreciated its beauty.
During my political voluntary year, my parents showed me an article about a small university in Bremen named after a famous coffee brand. This place sounded awesome and today I can say that finding this article was the best thing that could have ever happened then. I could not have imagined my undergraduate time any better (although it was a tough time too). The Hogwarts-like campus with its four colleges is very international, English-speaking and it offers an environment of excellent teaching and research. I made wonderful friends from all over the globe and had a lovely time.
There are levels of complexity I could have never imagined. In high school, I knew that proteins are made from mRNA which is made from DNA templates. Sounds simple if you don't consider capping, splicing, localized translation, translational recoding, mRNA editing, mRNA decay, silencing with miRNAs or siRNAs. Even miRNAs, the downregulators of mRNAs can be silenced by even other RNA species. Pretty cool, right?
When I searched for an interesting topic for my first internship, epigenetics in oncology crossed my search plenty of times. How fascinating, that a relatively new field revolutionized modern developmental biology and basic molecular research with such an impact. The central dogma of the determining nature of our genes is finally overruled and our environment and circumstances are now in the game. Finally, at the German Cancer Research Center (dkfz) in Heidelberg, I worked with non-coding RNAs and epigenetics. The group looked at nucleic acid triplexes recruiting DNA modifying enzymes like DNA methylases and investigated how environmental signals are conferred onto our genes and cells. My second internship in Cambridge was based in a similar field. I worked on transgenerational epigenetic inheritance using the model organism Caenorhabditis elegans. Finally for my third oncology internship in Singapore I studied long non-coding RNAs in breast cancer.
For my undergraduate thesis, I worked on the Elongator complex in Dictyostelium discoideum, the social amoeba. This thesis was my first experience in translational control and I continued in that area for my Master's in Cambridge where I worked on protein trans-activation of programmed ribosomal frameshifting. A depiction of the mechanism I worked on is shown below for a porcine virus.
Either a complex structure formed by a nucleic acid stretch or a protein complex blocks elongation during translation leading to the production of an alternative protein. Pretty fancy what viruses but also cells came up with during evolution.
For further research on translation and RNA biology I moved to the Max-Planck-Institute for Developmental Biology in Tübingen to work with famous RNA biochemist, Elisa Izaurralde. I worked on the initiation of translation. In particular, I worked on a large scaffolding protein, the eukaryotic initiation factor 4G (translation initiation with eIF4G depicted below).
For this project I worked with X-Ray Crystallography and did in vitro and in vivo protein interaction studies (ITC, IPs, pulldowns). Unfortunately, Elisa Izaurralde died very unexpectedly from cancer in April 2018.
Afterwards I relocated to the University of Basel (Department of Chemistry) to Thomas Ward`s lab to work on artificial metalloenzymes (ArMs) in bioengineering. I work on three different ArM scafolds:
A) Streptavidin where I work with 135 rational design enhanced variants in deallylation, metathesis and transfer hydrogenation. I am creating enzymes with a shielded environment for a catalyst of a chemical reaction (see picture below).
B) Human Carbonic Anhydrase which is a relevant protein on cancer cell surfaces and thus plays an important role in oncology research.
C) HaloTag into which I introduced four unnatural amino acids and did structural biology for an enhanced fluorescent reporter based on HaloTag.
