Research Ewa Sieliwonczyk

Abstract

Sudden death in the young is primarily caused by inherited diseases of the heart. These conditions are frequently caused by mutations in genes responsible for maintaining a regular heartbeat. Many genes that can cause sudden death have already been identified. However, for an important portion of patients, the genetic test reveals a genetic variant with unknown significance. With my project, I intend to create a new model to study the effects of these mutations on the heart in vivo. For this purpose, I will generate a new zebrafish line, in which cardiac electrical and chemical calcium signals will be converted into fluorescent light signals. As zebrafish are translucent during the first days of development, this animal model lends itself perfectly to visualize these signals in vivo. I will use the new zebrafish line to improve our understanding of one specific cardiac disorder, catecholaminergic polymorphic ventricular tachycardia (CPVT). This condition is characterized by abnormal calcium signaling in the heart, and as such my method will be highly suitable to study CPVT. Both in the literature and in our own cardiogenetics clinic, several CPVT families with an uncertain inheritance pattern have been discovered. With my assay I intend to expose the mechanisms of CPVT in these families and hereby clarify the results of the genetic tests and contribute to future diagnostic testing in CPVT.

Researcher(s)

• Promoter: Loeys Bart
• Co-promoter: Alaerts Maaike
• Co-promoter: Schepers Dorien
• Fellow: Sieliwonczyk Ewa

Research team(s)

Project type(s)

• Research Project

Abstract

Sudden death in the young is primarily caused by inherited diseases of the heart. These conditions are frequently caused by mutations in genes responsible for maintaining a regular heartbeat. Many genes that can cause sudden death have already been identified. However, for an important portion of patients, the genetic test reveals a genetic variant with unknown significance. With my project, I intend to create a new model to study the effects of these mutations on the heart in vivo. For this purpose, I will generate a new zebrafish line, in which cardiac electrical and chemical calcium signals will be converted into fluorescent light signals. As zebrafish are translucent during the first days of development, this animal model lends itself perfectly to visualize these signals in vivo. I will use the new zebrafish line to improve our understanding of one specific cardiac disorder, catecholaminergic polymorphic ventricular tachycardia (CPVT). This condition is characterized by abnormal calcium signaling in the heart, and as such my method will be highly suitable to study CPVT. Both in the literature and in our own cardiogenetics clinic, several CPVT families with an uncertain inheritance pattern have been discovered. With my assay I intend to expose the mechanisms of CPVT in these families and hereby clarify the results of the genetic tests and contribute to future diagnostic testing in CPVT.

Researcher(s)

• Promoter: Loeys Bart
• Co-promoter: Alaerts Maaike
• Co-promoter: Schepers Dorien
• Fellow: Sieliwonczyk Ewa

Research team(s)

Project type(s)

• Research Project