Menachem Viktor Khamo Sarusie - Postdoctoral Fellowship 2023
Project summary:
The role of ciliary genes in congenital heart disease comorbidities
We hypothesize that a significant part of neurodevelopmental disability in congenital heart disease patients are caused by perturbation of cilia-related genes involved in development of both heart and brain. In our project we will characterize cilia gene candidates in vitro and in vivo and identify genenetworks perturbed by cilia-related candidate genes involved in both heart and brain development.
Project Title
The role of ciliary genes in congenital heart disease comorbidities
Background
Cardiovascular health is associated with cognitive and mental health, yet little is known about the genetic and phenotypic link between the heart and brain during development and disease. Genetic variants that impair formation and function of the primary cilia cause severe human syndromes with overlapping phenotypes including congenital heart disease with neurodevelopmental disability.
Aim
The overall aim of this project is to investigate the role of ciliary genes in congenital defects of the heart and brain.
Methods
We will initially do a quick screen of our candidates in zebrafish using CRISPR/Cas9 in F0 prior to establish stable lines. The best candidates will be evaluated further for cilia expression in heart and brain tissues and characterized with transgenic lines, whole-organ imaging, behavioural assays and spatially resolved transcriptomics (SRT) to identify perturbed gene-networks in organ development.
Preliminary results
Our preliminary findings shows that the severity of mutations in cilia-related genes are enriched in a large CHD patient cohort and that 27 of these genes are significantly expressed in the heart and brain. We further demonstrate that one of these candidates localize to the primary cilia during heart and brain prenatal development and when perturbed causes heart and brain malformations in zebrafish.
Menachem Viktor Khamo Sarusie
- MSc and PhD
- University of Copenhagen
Main supervisor:
Lars Allan Larsen, Professor, Medical Genetics Program, University of Copenhagen
Co-supervisor:
Søren Tvorup Christensen, Professor, Cell Biology and Physiology, University of Copenhagen