Disciplines
Developmental Biology
Abstract (300 words maximum)
Congenital heart defects are often identified during pregnancy or infancy and are the most common birth defect presented in humans, affecting blood circulation resultant from small holes in a blood chamber to deformity-inducing missing structures. Recent advancements in medicine have allowed those affected to live healthier, longer lives. Gene combinations and chromosomal changes play pivotal roles in congenital heart defects, but the specific genes involved remain unknown. The Nowak Lab has discovered several novel regulatory proteins that are critical for embryonic heart development and is studying them for a potential link to congenital heart defects.
During embryogenesis, the heart of Drosophila melanogaster and the human heart develops into a two-chambered tube. The genes, gene products, and morphogenetic events directing this process remain consistent in both insects and humans. In Drosophila, the process of heart specification and formation is entirely controlled by several transcription factors that work together with the nuclear co-factor, Akirin, to mediate cardiac gene expression. By working together with the Nucleosome Remodeling and Deacetylase (NuRD) complex, Akirin is able to regulate gene expression. Embryos bearing mutations in different NuRD subunits produce hearts that are severely misshapen, poorly patterned, and have reduced numbers of cardio myoblasts in the finished organ.
For my project, I will use forward genetic techniques alongside confocal-based embryo imaging to quantify, characterize, and categorize the various types of heart formation defects that we observe in NuRD complex mutants. Finally, I will use live confocal-based imaging to assess whether these mutant hearts, with their cardiac defects, are capable of coordinated contraction and/or blood flow. Most importantly, these findings will give us direct insights into the possible role of Akirin/NuRD interactions in the heart function of humans.
Academic department under which the project should be listed
Molecular and Cellular Biology
Primary Investigator (PI) Name
Dr. Scott Nowak
Included in
The Role of Akirin/NuRD Interactions During Heart Development
Congenital heart defects are often identified during pregnancy or infancy and are the most common birth defect presented in humans, affecting blood circulation resultant from small holes in a blood chamber to deformity-inducing missing structures. Recent advancements in medicine have allowed those affected to live healthier, longer lives. Gene combinations and chromosomal changes play pivotal roles in congenital heart defects, but the specific genes involved remain unknown. The Nowak Lab has discovered several novel regulatory proteins that are critical for embryonic heart development and is studying them for a potential link to congenital heart defects.
During embryogenesis, the heart of Drosophila melanogaster and the human heart develops into a two-chambered tube. The genes, gene products, and morphogenetic events directing this process remain consistent in both insects and humans. In Drosophila, the process of heart specification and formation is entirely controlled by several transcription factors that work together with the nuclear co-factor, Akirin, to mediate cardiac gene expression. By working together with the Nucleosome Remodeling and Deacetylase (NuRD) complex, Akirin is able to regulate gene expression. Embryos bearing mutations in different NuRD subunits produce hearts that are severely misshapen, poorly patterned, and have reduced numbers of cardio myoblasts in the finished organ.
For my project, I will use forward genetic techniques alongside confocal-based embryo imaging to quantify, characterize, and categorize the various types of heart formation defects that we observe in NuRD complex mutants. Finally, I will use live confocal-based imaging to assess whether these mutant hearts, with their cardiac defects, are capable of coordinated contraction and/or blood flow. Most importantly, these findings will give us direct insights into the possible role of Akirin/NuRD interactions in the heart function of humans.