Molecular Genetics of Neurobiology and Neurological Diseases
The goal of our lab is to develop new molecular genetic tools to understand the pathophysiology of neurodegenerative diseases, and normal functions of the affected brain regions at molecular, cellular and circuitry levels.
- We established a novel method of establishing mouse models through Bacterial Artificial Chromosome (BAC) modification and transgenesis. This method has several unique advantages such as large insert capacity (up to 350 kb), faithful expression patterns, highly efficient modification for deletions, insertions, marker gene tagging, and point mutations. This allows us to perform very fine tuned molecular genetic experiments, and is especially powerful for modeling diseases.
- Using this method, we are establishing mouse models for Parkinson?s disease, Huntington's disease, and other neurodegenerative diseases.
- With these mouse models, we are addressing the following important questions: How much and where are the transgenes expressed, and are they correlated to the onset and severity of the mutant phenotypes? Is there a selective neuronal death in affected brain regions? What are the deficits in their motor function, learning/memory ability? What are the important domains in the disease proteins? What are the early pathological events at the molecular and cellular levels? Why there are selective cell deaths while the disease genes are universally expressed?
- Parallel to these mechanistic studies, we also started to use these mouse models for testing potential drugs and genetic modifiers.
- We are making an effort to develop a genetic method for gene expression/inactivation with simultaneous spatial, temporal control in an inducible and reversible manner. This method, if successfully established, will be a powerful tool for molecular genetics in general.