PhD defence Maria Suzanna Hubertina Stiekema

Keywords: Nuclear lamins, Merkel cell carcinoma, Laminopathies, Super-resolution microscopy

"Shedding Light on Lamins in Health and Disease"

Every human consists of trillions of organized cells. One of its components is the nucleus, which stores our genetic information. Nuclear lamins are proteins that form a network underneath the shell of the nucleus and are important for many cellular functions. This lamin network is extremely thin, about 5000 times thinner than a human hair. Defects in lamins can lead to different types of disease, together called laminopathies. Changes in lamins are also seen in other diseases, including several cancer types. 

This thesis investigated lamins in Merkel cell carcinoma (MCC), an aggressive skin cancer in which lamins had not been investigated before. This research revealed differences in the amount of lamins when comparing patient tissue of an original tumor and metastases. In cell cultures, the nuclear shape and response to damaged nuclei were different in the two types of MCC. Together, this implies that lamins effect the aggressiveness of MCC.

This thesis also describes the optimalization of so-called super-resolution microscopy techniques, to be able to investigate the thin lamina in more detail. These techniques apply new concepts to visualize more detail, which for example allowed to see changes between healthy and laminopathy cells better as compared to standard microscopy techniques.

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