The Stelzl Lab is a computational molecular life science and computational biophysics research group at the Institute of Molecular Physiology (imP), Johannes Gutenberg University Mainz, led by Prof. Dr. Lukas Stelzl.
We use multi-scale molecular simulations, from atomistic detail to residue-level coarse-grained models, to understand how biomolecular condensates and liquid-liquid phase separation regulate gene expression in health, ageing, and disease.
Our group investigates how dynamic self-organization gives rise to specific regulation in cells. Self-organization is ubiquitous in cells and essential for regulating biological processes in time and space. Proteins and nucleic acid fold and interact and self-assembly into large macromolecular complexes. Biomolecules also phase separate to form liquid biomolecular condensates. Notably, phase separation of proteins and specific recruitment of protein-RNA complexes by these phase-separated condensates underpins transgenerational epigenetic inheritance in C. elegans. By contrast, in neurodegenerative diseases such amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer’s disease phase separation is implicated in the formation of toxic aggregates. Liquid condensates, which have important functional roles, “age” on the molecular level and undergo a liquid to solid transition which results in toxic aggregates. Dysregulation of phase separation as cells age and the consequential formation of toxic aggregates may even be a general driver of aging.
We are using multi-scale molecular dynamics simulations (Fig 1) and machine learning to study intrinsically disordered and folded proteins, the effects of post-translational modifications on proteins, as well as protein-DNA and protein-RNA interactions. Cell rely fundamentally on chemical fuel (e.g. ATP) driven non-equilibrium processes and including such chemical-driven reactions in simulation models will aid our understanding of organization of biomolecules at the subcellular level. Simulations also help us to understand synthetic systems, which can aid our understanding of regulatory principles in cells. Our research is broadly organised along four research lines: 1) Phase separation of RNA binding proteins, 2) Multivalent interactions and condensation in transcription 3) Specificity in small interfering RNA pathways 4) Development of multi-scale simulation methods and integration of experiments and simulations.