Darcie L. Moore
Position title: Assistant Professor - Neuroscience
Phone: Phone: (608) 265-7836 | Fax: (608) 265-5512
RESEARCH INTERESTS - Neural stem cells and aging
We are a lab that gets excited about science. If you do too, please contact Dr. Moore for more information on specific projects.
Throughout life, stem cells are responsible for replenishing and regenerating tissue, fundamentally maintaining “youthfulness.” However, with aging, this ability is decreased, resulting in effects such as cognitive impairment, reduced immune response, deterioration of skeletal muscle, and difficulty in wound healing, for example. To develop methods to improve or rescue aging of somatic stem cells, we must understand not only how they age, but also how they remain young. Recently, we have shown that neural stem cells (NSCs) asymmetrically segregate cargoes (e.g. damaged proteins) when they divide, leaving one daughter cell more “clean” than the other. In addition, we have identified a diffusion barrier in the endoplasmic reticulum membrane in dividing NSCs that may limit the movement of these cargoes. Indeed, we have found that diffusion barrier strength weakens with age, correlating with a more symmetric distribution of aging factors, suggesting that this may be a mechanism for the segregation (Moore et al, 2015, Science).
In mammalian NSCs, the daughter cell which inherits the damage has a slower proliferation rate than the more “clean” daughter, suggesting that this process may be utilized by the cell as a method of cellular rejuvenation (Moore et al, 2015, Science). We hypothesize that stem cells use the asymmetric segregation of cargoes as a mechanism to remain “young,” and that loss of this asymmetry and the weakening of the diffusion barrier with age greatly contributes to the stem cell aging phenotype seen in the body.
The research in my lab focuses on identifying the mechanisms that stem cells use to create the asymmetric segregation of cargoes, to identify what other components are segregated, and to use this knowledge to improve stem cell aging. We use mammalian embryonic stem cells and adult neural stem cells as model systems in our research, with interest in broadening our somatic stem cell portfolio. We employ cell biology, biochemistry, molecular biology, genetics, and computational approaches to address our questions. Our lab specifically focuses on using advanced live imaging technologies, including FLIP, FRAP, photoactivation, 4D timelapse, and computer learning-based high-throughput imaging to interrogate cargoes in mitotic stem cells. If you can see it, you can believe it.
(Left: Click to enlarge) A mouse neural stem cell is seen in telophase in bright field. Shown in blue are the nuclei, and red are the ubiquitinated proteins. Note that the ubiquitinated proteins are asymmetrically segregated between the two daughter cells.
(Above) A dividing embryonic neural stem cell overexpressing vimentin-eGFP (green) and a membrane marker (Kusabira orange) outlining the cell, demonstrates an asymmetric distribution of vimentin to the non-stem daughter cell.