Lukas Stelzl
Phase Separation in Homeostasis and Age-Related Diseases
We want to elucidate how phase separation of proteins can be a regulatory mechanism of resilience and how dysregulation of phase separation contributes to age-related diseases. To uncover the molecular mechanisms of phase separation in homeostasis and age-related diseases, we employ particle-based multi-scale simulations, which span atomic resolution to cellular time- and length scales. 1) We want to understand how the phase separation of TDP-43, FUS, and Tau is progressively dysregulated in neurodegenerative diseases, including amyothropic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Alzheimer’s disease. 2) We want to compare and contrast instances where phase separation may constitute a molecular vulnerability, with cases where phase separation provides for robust regulation as in developmental biology.
We collaborate closely with Prof. D. Dormann and Prof. R. Ketting on phase separation in neurodegeneration and resilient regulation by phase separation.
Positions held
- Since 2020: ReALity Junior Group Leader and IMB Associate Group Leader, Faculty of Biology and KOMET1, Institute of Physics, Johannes Gutenberg University Mainz and Institute of Molecular Biology (IMB), Mainz
- 2015 - 2020: Postdoctoral fellow, Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Frankfurt am Main
Education
- 2015: PhD in Biochemistry, University of Oxford
- 2010: MBiochem, Molecular and Cellular Biochemistry, University of Oxford
Selected publications by Lukas Stelzl
Stelzl LS*, Pietrek LM*, Holla A, Oroz J, Sikora M, Köfinger J, Schuler B, Zweckstetter M and Hummer G (2022) Global structure of the intrinsically disordered protein Tau emerges from its local structure. JACS Au, 2:673–686 Link
Gruijs da Silva LA, Simonetti F, Hutten S, Riemenschneider H, Sternburg EL, Pietrek LM, Gebel J, Dötsch V, Edbauer D, Hummer G, Stelzl LS and Dormann D (2022) Disease‐linked TDP‐43 hyperphosphorylation suppresses TDP‐43 condensation and aggregation. EMBO J, 41:e108443 Link
Stelzl LS, Mavridou DAI, Saridakis E, Gonzalez D, Baldwin AJ, Ferguson SJ, Sansom MSP and Redfield C (2020) Local frustration determines loop opening during the catalytic cycle of an oxidoreductase. eLife, 9:e5466 Link