Project (Niels Fischer)
Molecular mechanisms of translation regulation in health and disease

Translation regulation - most of all translation initiation - plays a key role in defining the composition of the human proteome, while dysregulation of translation initiation has been implicated in various diseases ranging from cancer to viral infection and neurological disorders. In our group, we are combining cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET) with biochemical and biophysical approaches to resolve the structural dynamics and function of the intricate machineries driving translation regulation in health and disease in human cells. We recently established an in vitro human translation system, which allows us to assemble the complete multi-step pathway of translation initiation from purified components in the test tube, very much like a sophisticated “Lego brick” system.

Join us for a PhD to learn and apply cutting-edge structural biology and biophysics techniques in a highly supportive and collaborative environment. Dependent on your interests you may e.g. work on:
• how the complex initiation machinery regulates the human proteome and how cancer cells reprogram this machinery. In this area, you will reconstitute canonical and cancer-related translation regulation complexes in vitro, determine their molecular structures and dynamics by cryo-EM and characterize their function by biochemical and biophysical methods.
• exploring new pathways in disease and stress by perturbing translation regulation in vivo in human cells and visualizing the involved machineries in their cellular context by cryo-electron tomography (cryo-ET).
Feel free to contact for further information (niels.fischer@mpinat.mpg.de) - we are looking forward to welcome you in our team!





Homepage Research Group
https://www.mpinat.mpg.de/fischer



Publications:

• V Petrychenko, SH Yi, BZ Peng, D Liedtke, MV Rodnina, N Fischer. “Structural basis for translational control by the human 48S initiation complex.” Nat Struct Mol Biol (2024). https://doi.org/10.1038/s41594-024-01378-4
  
• SH Yi, V Petrychenko, JE Schliep, A Goyal, A Linden, A, A Chari, H Urlaub, H Stark, MV Rodnina, S Adio, N Fischer. “Conformational rearrangements upon start codon recognition in human 48S translation initiation complex.” Nucleic Acids Research (2022), 50 (9), 5282 – 5298. https://doi.org/10.1093/nar/gkac283
  

Full publication list: https://www.mpinat.mpg.de/3729717/publications