Details for Winnok De Vos

Researchgroup Cell Systems & Imaging
Function Guestprofessor
Phone +32-9-2645971
Office Block B, room 120.009
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General Description

Our research focuses on the analysis of the single cell in the context of laminopathies. To this end, we make use of genetic engineering, advanced light microscopy and image analysis. Due to this multidisciplinary expertise, the Cell Systems and Imaging researchgroup has fruitful collaborations with different partners in both academia and industry (among which with ESA on space related research projects). This unit also hosts and supports the faculty�s microscopy facility, LiMiD .


The nuclear envelope (NE) is a double lipid bilayer, which physically separates the nuclear contents from the cytoplasm. Only perforated by meticulously regulated nuclear pore complexes, the NE is the principal barrier coordinating bidirectional communication between the nucleus and cytoplasm of the cell. Directly underlying the double lipid bilayer is an intimately connected meshwork of intermediate filament proteins, the nuclear lamina, which provides structural support to the nucleus and has a central role in defining nuclear organization. Defects in its major constituents, the A-type nuclear lamins (encoded by the LMNA gene), lead to a spectrum of diseases collectively referred to as laminopathies. Disease manifestations range from systemic premature aging, such as observed in Hutchinson-Gilford Progeria Syndrome (HGPS), to muscular dystrophies and lipodystrophies. The causative mechanisms of disease in laminopathies are not yet completely understood, but in general lamin defects alter the physical integrity of nuclei, resulting in increased susceptibility to mechanical stress and alterations in (mechanosensitive) gene expression.

Broers, J.L.V., Hutchison, C.J. and Ramaekers, F.C.S. (2004) Laminopathies. Journal of Pathology, 204, 478-488.




Nuclear Dynamics

Disruption of the nuclear lamina directly affects nuclear structure and chromatin organization. To determine whether differential lamin A processing also has an influence on nuclear dynamics we have quantitatively compared nuclear deformation and chromatin mobility in fibroblasts from laminopathy patients with normal cells. To this end we, we made use of telomere- binding proteins, which we visualized with light-economical imaging techniques (CLEM) and analyzed with home-written cytometric analyses. We thereby distinguished different levels of nuclear plasticity and different regimes of telomere mobility. Because of the pivotal role of dynamics in nuclear function, these differences likely contribute to or represent novel mechanisms in laminopathy disease development. Currently, we are further investigating structural interactions and functional implications.

W. De Vos, R. Hoebe, G. Joss, W. Haffmans, S. Baatout, P. Van Oostveldt and E. Manders (2009). Controlled Light Exposure Microscopy Reveals Dynamic Telomere Microterritories Throughout the Cell Cycle. Cytometry Part A 75(5), p428-439.

W. De Vos, G. Joss, W. Haffmans, R. Hoebe, E. Manders and P. Van Oostveldt (2010). Four-dimensional telomere analysis in recordings of living human cells acquired with controlled light exposure microscopy. Journal of Microscopy 238(3), 254-264.

J. De Vylder, W. De Vos, E. Manders and W. Philips (2011). 2D mapping of strongly deformable cell nuclei based on contour matching. Cytometry Part A, 79(7), 580-588.

W. De Vos, F. Houben, R. A. Hoebe, R. Hennekam, B. Van Engelen, E. Manders, F. Ramaekers, J. Broers and P. Van Oostveldt (2010). Increased plasticity of the nuclear envelope and hypermobility of telomeres due to the loss of A-type lamins. Biochimica et Biophysica Acta � General Subjects 1800(4), p. 448-458.




Nuclear Compartmentalisation

It is widely accepted that the nuclear membrane becomes dramatically affected in laminopathy cells. However, little is known about the implications of these structural alterations of the nuclear envelope for nucleocytoplasmic communication. To investigate whether LMNA mutations affect nucleocytoplasmic communication, we quantitatively compared nuclear permeability and retention using genetic reporter constructs and live cell imaging. This way, we could demonstrate that different mutations of A-type lamins cause intermittent, non-lethal ruptures of the nuclear envelope, which lead to temporary exchange of normally confined proteins between nucleus and cytoplasm, as well as permanent translocation of nuclear protein complexes to the cytoplasm and vice versa. Since this phenomenon was observed in all laminopathy variants examined, albeit with varying severity, our data suggest that nuclear rupture and loss of compartmentalization may add to cellular dysfunction and disease development in various laminopathies.

W. De Vos, F. Houben, M. Kamps, J. Cox, P. Van Oostveldt, V. Verstraeten, M. van Steensel, C. Marcelis, A. van den Wijngaard, F. Ramaekers and J. Broers (2011). Repetitive Disruptions of the Nuclear Envelope Invoke Temporary Loss of Cellular Compartmentalization in Laminopathies. Human Molecular Genetics, 20(21), 4175-4186.