A Quantitative Study by Array Tomographic Florescent In Situ Hybridization

by Gordon Wang, 8/1/2008

Fragile X syndrome is caused by the malfunction of a fundamental cellular process, the ability of cells to regulate spatially distinct pools of messenger RNA (mRNA). One of the cell types most affected is the neuron. This highly asymmetric cell type relies upon a tightly orchestrated network of proteins and RNAs to acutely and focally deal with its basic function, which is to process incoming information and to propagate it with fidelity. Defects in this regulatory network, however small (for example, Fragile X syndrome is caused by the loss of a single RNA binding protein) can have complex and life altering consequences. In the case of Fragile X, the result is mental retardation.

One of the major obstacles to treating Fragile X is in understanding the identities of the mRNAs disturbed, and where this disturbance is occurring. Our research will focus on the development of florescent in situ hybridization and Array Tomography, a new high resolution imaging paradigm, to quantify the nature of this disruption through high resolution and high throughput visualization of proteins and mRNAs on a subcellular level. This will allow us to determine, in intact tissue, the identities of the affected mRNAs and the nature of their affliction. This will help us better understand the root causes of Fragile X syndrome and to design targeted treatments.