Decoding plexins activation by chemo- and mechanosignals

• Applicant: Maria Florencia Sánchez, Ph.D.
• Subject Area: Biochemistry ; Biophysics ; Cell Biology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 522662095

Cells sense their environment, receive, and process a diverse set of chemical and mechanical signals through transmembrane receptors. The way how receptors sense and integrate these signals to orchestrate a wide variety of physiological processes remains one of the biggest questions in biology. Plexins function as receptors for semaphorins, molecules acting as cell guidance cues. Plexins thus regulate the shape and motility of cells during the development of the nervous and cardiovascular systems, and play important roles in many pathophysiological processes, including cancer, immunological and neurological diseases. However, it remains elusive how plexin oligomerization modulates downstream signaling. In particular, there is a lack of connection between the size and distribution of plexin clusters, mechanical signals, and the impact on the cellular activity. To bridge this gap, the proposed project will enable to interconnect these aspects via new multidisciplinary approaches to understand critical functions of plexin-semaphorin signaling. This multi-pronged project is focused towards creating an innovative toolset that will transform the current biotechnological landscape. I will develop a suite of nanotechnological matrices to mimic cell-cell interfaces. These matrices will allow high spatial control of the number of ligands, and also display 3D nanotopographies. Using these matrices as counterparts, I will unravel early downstream signaling events upon in situ receptor activation in engineered cells expressing photo-controlled plexins. My group will use modern techniques ranging from 3D microprinting, DNA-origami, and optogenetics to live-cell microscopy. The knowledge and tools designed in this project will advance the state-of-the-art and bring unprecedented insights in plexin signaling and mechanosensing.

• DFG Programme: Independent Junior Research Groups