Damien D’Amours and his team at the Ottawa Institute of Systems Biology needed three years to discover the molecular defects associated with LIC Syndrome, a real genetic disorder that affects young children and their children. causes severe respiratory distress, immunodeficiency and extreme chromosomes.
Augmentation of symptoms occurs in the first months after birth in infants suffering from Immunodeficiency lung disease and chromosome rupture (LIC). Patients typically suffer from immune failure and deficiency, which can progress to pediatric lung disease in early childhood. The disease is caused by inactivated small mutations in NSMCE3, a gene that encodes an essential trait found in the nucleus of human cells.
This research represents one of the most important milestones in the development of therapies to improve the lives of patients with LIC syndrome. Damien D’Amours is a full professor in the Department of Cellular & Molecular Medicine of the Faculty of Medicine whose laboratory aims to understand the mechanisms that cells use to promote efficient cell division and proliferation. He provided further insight into the findings of the study.
What exactly did you find?
“We discovered how deficiencies in the“ DNA stress ”mechanism within our cells could kill a rare genetic disorder in young children (i.e., the LIC syndrome). We found the molecular cause by using an exciting combination of biology, advanced genetics and classical biochemistry to prove that an enzyme has a rare ability to compress DNA within our cells. “
How did you do it?
“We developed a completely new system to clean human enzyme that no one in the world has ever purified – the“ Smc5 / 6. ”The Smc5 / 6 complex is an important influence on chromosome integrity, and let our breakdown revealed the structure of the enzyme and its powerful ability to condense the structure of DNA in space. We then explained the mutations causing the LIC syndrome in our system and showed that the mutations affect the ability of the Smc5 / 6 center to repair chromosomes in cells, thus explaining how mutations LIC affects the ability of cells to maintain healthy genomes. “
You used the “systems biology” approach to reach your conclusions; explain this.
“The advent of systems biology has revived biochemical research in recent years. This approach relies on the use of integrated” omics “technologies and organic models to enhance systems-level understanding. about human diseases. (Omics is a general term for describing “large-scale genomics, proteomics, and metabolomics technologies.”) The University of Ottawa has been at the forefront of our in research with the creation of the Ottawa Institute of Systems Biology (OISB) .We took advantage of a systems biology approach to develop completely new systems for purifying enzymes that have never been purified before. .We then used an innovative combination of classical biology, proteomics and biochemistry to reveal the mode of action of the Smc5 / 6 complex and how mutations in this complex can cause major deficiencies in DNA repair. “
Why is this an important finding?
“My research team and colleagues are conducting research at the very beginning of our field and, as a key laboratory on this project, we feel that our research represents one of the most important milestones on the path to designing treatments for patients with LIC syndrome. Prior to our work, no one knew the biochemical cause of the LIC syndrome and how the mutated enzyme in this disease could affect patient / child cells; we have provided answers to these fundamental questions. “
Source:
Magazine Reference:
Serrano, D., et al. (2020) The Smc5 / 6 Core Complex is a structure-specific DNA binding and compression device. Cell molecular. doi.org/10.1016/j.molcel.2020.11.011.