Simons Foundation

A central goal in neuroscience is determining the genetic basis of neurological disorders — from autism to brain tumors. Many of these pathological states result from defects in gene regulatory programs that are fundamental to all cell types but lead to dysfunction specifically within the nervous system. Gail Mandel investigates the basis of this phenomenon and has identified cell-cell interactions between neurons and glia involved in pathological states of brain development. Mandel has ameliorated the neuropathology of one autism spectrum disorder, Rett syndrome, by genetically replacing the defective MeCP2 gene with a good copy of the gene in astrocytes – glia cells in the brain. She is now exploring the underlying mechanisms crucial for neuronal signaling.

Although most people regularly tune up their cars, you probably haven’t needed to bring your brain in for a tune-up, despite the fact that the human brain is far more complex than the internal combustion engine. What’s more, unlike most machines, your brain is constantly changing in order to store memories and adapt to a fluid environment. Our brains are faced with a fundamental challenge: They must preserve the integrity of the neural circuits that subserve behaviors over the lifetime of an organism, while at the same time allowing plastic mechanisms to shape and fine-tune their function.