Tracking DNA Organization During Embryo Development and Disease Progression
“I’ve always been fascinated by chromosomes,” says 4D Nucleome researcher Dr. Christine Disteche. And with good reason: chromosomes contain all the genetic information necessary to control cell function and development. As an embryo grows, complex processes of molecular signaling direct what kind of cells and organs will develop by controlling which genes are turned on and off. The way that chromosomes, and the DNA they contain, are organized inside the cellular nucleus may have a role in determining cell development as part of these processes. Dr. Disteche, as part of the University of Washington 4-Dimensional Genomic Organization of Mammalian Embryogenesis Center, is studying the mechanisms behind embryo development and what role DNA organization plays in determining cell fate. The ambitious project combines many different types of analyses that follow cells in mouse embryos as they grow and mature. The researchers are studying how different cell types develop by measuring the activity of genetic pathways within individual cells and combining those results with where those cells are in the embryo and how their DNA is organized. This project is one of the first to study these processes in living embryos, with previous work focusing only on cultures of isolated cells.
Dr. Disteche’s research has benefited from the new tools and resources that are being created by the 4D Nucleome program. She reflects that, when the program started, “it was like all of a sudden I had all these things that could be done to really look at the nucleus and look at the chromosomes and see their structure at the molecular level.” These new methods to track cell type-specific development and monitor DNA organization will allow her team to understand the underlying processes of how genetic mutations lead to different DNA arrangement in the nucleus that can cause diseases. She is interested in sex-linked genes and their roles in sex-based differences in diseases, particularly those found on the X chromosome, as well as imprinting disorders caused by incorrect activation or silencing of parental genes. Finding new methods to modify how DNA is organized in the nucleus could help find potential treatment strategies for these diseases.
Dr. Disteche has always been driven by her curiosity. Her journey into research was inspired both by an innate desire to understand the world around her as well as both of her parents, who were also in academia. Her mother in particular was a role model, as she was a chemist at a time when the field was heavily male-dominated. Dr. Disteche reflects that “she gave me a lot of confidence that I could do everything just like the boys would do it.” Now a mentor to her own trainees, Dr. Disteche stresses the importance of being excited by the questions that they are pursuing, and always encourages her students to take on projects of interest even if the path is challenging.
Learn more about the research of Dr. Disteche and her collaborators here.