PhD: Dynamics of proteins in cell nuclei studied by super-resolution microscopy

In order to keep human bodies healthy, cells have to continuously adjust to stress, such as DNA damage, nutrient deficiency and mechanical stress. Recently, the lamin family of cytoskeletal proteins have emerged as a key regulator of cell response to intrinsic and environmental stimuli. Lamins are the main architectural proteins of the nucleus and form a fibrous, highly stable meshwork underlying the inner nuclear membrane. The cell’s stress response triggers one of the lamin types, prelamin A, to accumulate, which affects important cellular processes such as cell cycle progression, DNA-replication, chromatin remodeling and senescence.

Fundamental knowledge on the lamin-dependent regulatory mechanism that controls DNA replication, and replication fork stalling leading to cell senescence, is still lacking. DNA replication is a process fundamental to all life, and lamins have been found to regulate DNA replication through local chromosome compaction and direct interaction with the replication proteins. Furthermore, during S phase, the nucleoplasmic distribution of lamins changes with altering patterns of DNA replication. This suggests an important role in the highly complex logistics of organizing the replication of a megabase genome distributed over dozens of chromosomes. In this project, we aim to obtain fundamental understanding of the lamin-regulated replication fork positioning and stalling which could greatly enhance our knowledge of pathogenic conditions underlying ageing and cancer.

We, the Geertsema lab, are an experimental biophysics lab employing fluorescent imaging techniques to improve understanding of cellular structures at the nanometer scale. As a recently started research group, we offer an interactive, supportive and collegial environment. We perform multidisciplinary research where we combine techniques from biophysics, microscopy, cell biology, biochemistry and protein engineering.

The Geertsema lab is embedded in the Imaging Physics Department of the TU Delft, which focuses on developing and implementing novel imaging technologies. The department features an inspiring, welcoming and pioneering environment for researchers that want to push the boundaries and implementation of current imaging systems.