Research
By Raymond on Feb 28, 2009 in Lab
Undergraduate Lab at Tsinghua University
Research
Alzheimer’s disease, or AD
We have transgenic flies which express human Aβ42 or its mutant forms, which can be directly driven in fly neurons using UAS-GAL4 gene switch. These flies have defects in olfactory learning, memory and lifespan. Amyloid deposits and neurodegeneration appear when they get old, as revealed by immunostaining and brain sections. Using this model, we can examine the molecular mechanisms underlying AD by genetic screens. For instance, we are testing whether the insulin pathway interacts with Aβ42 in memory defects, and how are cell cycle related factors related to Aβ42 in leading to cell death in AD.
Olfactory memory in Drosophila
Flies do have memory. It is generally classified into 5 types of memory, including short term memory which extinguishes within hours, anaethesia-resistant memory produced by mass training, and long term memory which require space training and protein synthesis. Drosophila is a powerful genetic tool which allows us to screen for mutants related to these memories. A former colleague has shown that AKAP in PKA pathway of mushroom body neurons are essential for long term memory. Shuai has found out that Rac, a small rho GTPase, is responsible for active erasure of early phase memory, which may explain why short term memory is short term. Besides associative learning, we would also like to explore further in trace conditioning.
Schizophrenia
Dysbindin is a susceptible gene in schizophrenia. Its knockout in Drosophila has defects in olfactory memory and electrophysiology. Interestingly, the mutant also possesses male-male courtship behavior, which may be related to the glutamate pathway. By this, we are trying to set up a Drosophila behavior model for schizophrenia. Actually, homologs of many schizophrenia susceptible genes cannot be found in fly. It may indicate genes related to higher cognitive functions are evolved in later stages.
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