Genes aren’t everything…
Exactly, the issue of control or regulation exists in every organism: it must constantly know when to regenerate which cells in different organs in such a way that it does not produce too many new cells, but also not too few. A malfunction here can lead to the formation of tumours. However, it is also extremely important, even in the very earliest stages of embryonic development, that the cells know what the plan is – so that cell lines with different cell types are formed from a single fertilised egg. For example, we have investigated the question of how the early cells decide whether to become the embryo or to form the supporting tissue, i.e. the placenta. The first cell lines divide very early on, before implantation in the uterus even takes place. We have discovered that certain enzymes influence gene regulation in this process: if you manipulate these enzymes, you also manipulate the decision regarding cell type. Ultimately, I am always concerned with the question of how cells, at the molecular level, receive, store, transmit and interpret information at any given time. One can imagine this as a kind of cellular memory, in which a cell’s states and previous decisions are represented at the molecular level – within the context of this existing information, the cell then interprets new signals it receives.
What is new about the methods you have developed for your research?
We do not use actual embryos, but rather cell-based model systems or so-called in vitro cell cultures of pluripotent stem cells, which represent the early, undifferentiated cells. Synthetic biology comes into play when we want to control or analyse processes within cells with a very high degree of precision, for example by rapidly switching genes on and off using light or chemical molecules introduced into the cell culture. Here, synthetic biology offers new approaches that are particularly rapid and precise. We spend a lot of time thinking about how we can capture epigenetic processes in a cell in a dynamic way, rather than just taking a static snapshot. It enables us to use the new methods to ask new biological questions: What exactly happens from the moment a signal reaches the cell until it decides to activate new genes or not? How is epigenetic information passed on across cell divisions? In addition to precise manipulations of the cells, we use various omics technologies from systems biology, which allow us to take a holistic look at what happens in the cell following a manipulation at the level of proteins, the genome, gene expression… Here in Freiburg, we have an excellent infrastructure for this; this includes a new mass spectrometer, which we were able to purchase thanks to funding from the Alexander von Humboldt Professorship. This makes it possible to identify and precisely quantify thousands of proteins that exist in the cells.