Molecular mapping of nuclear organization through quantitative nanoscale imaging

Dr. Johannes Stein

The organization of the human genome within the nucleus is critical for its function in health and is often misregulated in disease. Although genomics and imaging technologies have greatly expanded our understanding of genome structure and function, our molecular view of nuclear organization at the single-cell level remains incomplete. A major limitation is that conventional light microscopy lacks the resolution to reveal how proteins, RNA, and DNA interact to regulate genome organization and function. The Stein Lab addresses this challenge by developing and applying single-molecule fluorescence and super-resolution microscopy techniques to directly visualize how biomolecules spatially organize and interact within the nucleus. With these tools, we investigate fundamental processes such as chromatin folding mediated by cohesin and CTCF (Project 1), the roles of nuclear compartments like nuclear speckles in gene expression and splicing (Project 2), and how the molecular patterns of nuclear organization change in health and disease. Ultimately, our goal is to establish structural and mechanistic frameworks that link nuclear organization to cellular function.

The Stein Lab is building an interdisciplinary group and welcomes applicants from biology, (bio)chemistry, physics or engineering. Candidates will learn to use DNA Nanotechnology and cutting-edge single-molecule fluorescence microscopy techniques. Prior microscopy experience is beneficial but not required.

For more information, visit the Stein Lab.

Reference:

J. Stein°, M. Ericsson, M. Nofal, L. Magni, S. Aufmkolk, R. B. McMillan, L. Breimann, C. P. Herlihy, S. D. Lee, A. Willemin, J. Wohlmann, L. Arguedas-Jimenez, P. Yin, A. Pombo, G. M. Church° and C.-t. Wu°. Cryosectioning-enhanced super-resolution microscopy for single-protein imaging across cells and tissues. Proceedings of the National Academy of Sciences. 2025, 122 (32) e2504578122.