Mammalian Synthetic Biology
The Synthetic Biology lab aims at understanding how complex cellular processes are orchestrated at the level of molecular parts and circuits, dissecting signaling pathways that determine cellular decision making (e.g. response to different stresses) and developing strategies to efficiently re-wire and control cellular networks. To this end, we create tools and methodologies to artificially regulate the activity of selected proteins. Furthermore, we devise strategies for engineering novel molecular circuits and operating them in mammalian cells.
Therefore, our lab has two major areas of focus: learning about the fascinating processes underlying eukaryotic life (as well as de-regulation in diseases) and enabling their targeted manipulation for useful purposes, e.g. for basic research or therapeutic applications.
Our lab frequently uses light to interrogate or control molecular pathways of interest. Compared to chemical triggers, light can be easily applied at high spatial (nanometer) and temporal (millisecond) resolution while being non-invasive. Therefore, it is the ideal trigger for perturbing selected pathways with subcellular precision and in real time. To translate the light input into a signal that can be readily interpreted by cells, we employ photoreceptors derived from bacteria, fungi and plants and couple them to selected proteins to control their activity. We can, for instance, regulate gene expression with light by controlling the nucleocytoplasmic trafficking of transcriptional regulators fused to an engineered photoreceptor. The video on the right examplifies this strategy. Cells are expressing a fluorescent protein fused to the modified photoreceptor enabling light control of nuclear export. Selected cells irradiated with a blue laser beam (green circles) show rapid and reversible nuclear export of the fluorescent protein. Generally, we are eager to establish widely-applicable strategies for controlling selected cellular pathways from outside with high precision and minimal intervention.
Help unlocking nature’s treasure trove
We are fascinated about the fact that DNA – the genetic code - is a universal information carrier employed by all living entities known today. Genetic information can often be successfully transferred from one organism to another even over surprisingly large evolutionary distances. Ever-growing DNA sequence databases thus offer an enormous treasure trove of potentially useful genetic code. Moreover, massive progress has lately been made in the way custom, artificial DNA code can be written (synthesized) and operated in a recipient cell. This is due to improvements in chemical DNA synthesis, the emergence of efficient gene editing technologies such as CRISPR/Cas9 and TALENs as well as the development of new tools for the delivery of genetic information (e.g. viral vectors) and its artificial regulation from outside of a cell. In fact, synthetic biology already began to transform biology into an engineering discipline in order to rationalize and simplify the development of new biological systems. But despite the great progress, we are not quite there yet.
We want to make a significant contribution to this exciting transition and aid unlocking nature’s treasure trove for human benefit. If you are passionate about engineering new biological systems in a small team of equally passionate scientists, then join our new synthetic biology team @eilslabs.