The Project
Regulation of quiescence in adult hippocampal neural stem cells.
Winner
Dr Dieter Chichung Lie
GSF-National Research Center for Environment and Health
Ingolstädter Landstrasse 1
Munich Neuherberg D-85764
Germany
http://www.gsf.de/idg
Dr Dieter Chichung Lie is a thirty-five year old German neurobiologist who is working as a Group Leader at the Institute of Developmental Genetics of the GSF-Research Center, Munich, in the area of adult neural stem cell biology. He gained his Medical degree from the RWTH Aachen, Germany, and completed his Postdoctoral Fellowship at The Salk Institute for Biological Studies in La Jolla, USA, between 1999 and 2005 under the guidance of the eminent Dr Fred Gage. A highly respected researcher in his own right, Dr Lie is author or co-author of a string of papers published in Nature magazine, which examined the cellular and molecular mechanism underlying neural stem cell regulation.
He said: "I am really excited about this award. This is a wonderful opportunity to build a competitive research team in the European Research environment to investigate the biology of adult neural stem cells."
Provisional Award
€ 1,250,000
Project Description
Neural stem cells are undifferentiated cells that have the unique capability to self-renew and to differentiate into all major cell types of the central nervous system. During adulthood, neural stem cells contribute to hippocampal function by continuously generating new hippocampal dentate granule neurons.
Maintenance of the adult neural stem cell population is required for the generation of adequate numbers of new hippocampal neurons throughout lifetime. Recent evidence suggests that the balance between quiescence and proliferation is crucial for neural stem cell maintenance and that incomplete maintenance of the stem cell pool and the resulting decrease in neurogenesis may contribute to age-related decline in hippocampal function.
The overall aim of this project is to characterize the signaling pathways regulating quiescence of adult hippocampal neural stem cells, specifically focusing on the role on the Wnt/βcatenin2 and FoxO pathways. Preliminary findings indicate that these pathways are active in quiescent neural stem cells, that Wnt/βcatenin signaling and FoxO transcription factors can synergistically enhance the expression of cell cycle inhibitors and inhibit neural stem cell proliferation, and that inhibition of Wnt-signaling results in the loss of quiescent hippocampal neural stem cells.
The interaction of these pathways in neural stem cell quiescence will be investigated using a combination of cellular and molecular in vitro approaches and transgenic in vivo approaches. In addition, we will identify and functionally characterize new targets of Wnt/βcatenin and FoxO interaction to begin to elucidate the cellular machinery underlying quiescence in adult neural stem cells. These studies will not only contribute to a better understanding of the molecular mechanisms underlying neural stem cell quiescence but may also lead to new strategies that aim at the preservatioin of hippocampal function during aging through enhanced stem cell maintenance and preservation of hippocampal neurogenesi
- 1 The hippocampus is a part of the brain which plays a major role in learning and memory.
- Wnt proteins are a family of highly conserved secreted signaling molecules that regulate multiple cellular processes during embryogenesis.
