Gaëlle Houthaeve


 2016: Master of Science in Biochemistry and Biotechnology, Ghent University, Belgium. Performed the master thesis titled ‘GPCR heterodimerization and its role in the central nervous system’ on Erasmus in the Neuropharmacology and Pain research group of Prof. Dr. Francisco Ciruela at the University of Barcelona, Spain.

 Research interests:

 Accelerated aging diseases, neurodegenerative diseases, cell death, nuclear envelope rupture and repair, nuclear lamina, lamins, laminopathies

 Scholarship :

 Ph.D. fellowship of the Research Foundation-Flanders (FWO)

 Summary of Research Project:

 My research focuses on elucidating the direct causes and consequences of nuclear envelope (NE) ruptures that take place during interphase.

 The nuclear envelope (NE) has long been thought to only dismantle during mitosis in a highly regulated manner. However, recently it has been demonstrated that the NE can also transiently rupture during interphase [1-3]. This phenomenon is first and foremost promoted by a weakened nuclear lamina, but also compressive forces have been shown to take on a prominent role. Importantly, these events are transient, indicating the existence of a dedicated nuclear envelope repair machinery that operates during interphase. Although cells do not die after rupture, they do not get through these events unharmed. Indeed, the resulting loss of nuclear compartmentalization causes illegitimate exchange of cytoplasmic and nuclear components and can thereby impact genome integrity in various ways.

 Current knowledge concerning the mechanisms of rupture and repair, and the consequences for the cell is still limited. Studying spontaneous ruptures as they occur for instance in cells from laminopathy patients, can give information about the kinetics of rupture and repair. However, because of the stochastic nature and variable frequency of spontaneous ruptures, it is difficult to study close-to-immediate downstream effects. Therefore, we aim at developing a technique to induce nuclear ruptures in a controlled manner.

  [1]      De Vos WH, Houben F, Kamps M, Malhas A, Verheyen F, Cox J, Manders EMM, Verstraeten VLRM, van Steensel MAM, Marcelis CLM, van den Wijngaard A, Vaux DJ, Ramaekers FCS, Broers JLV (2011) Repetitive disruptions of the nuclear envelope invoke temporary loss of cellular compartmentalization in laminopathies. Hum Mol Genet 20, 4175–4186.

[2]      Robijns J, Molenberghs F, Sieprath T, Corne TDJ, Verschuuren M, De Vos WH (2016) In silico synchronization reveals regulators of nuclear ruptures in lamin A/C deficient model cells. Sci Rep-Uk 6, 30325.

[3]      Denais CM, Gilbert RM, Isermann P, McGregor AL, Lindert te M, Weigelin B, Davidson PM, Friedl P, Wolf K, Lammerding J (2016) Nuclear envelope rupture and repair during cancer cell migration. Science 352, 353–358.