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2016 Grants - McIntire
Functional Genetic CRISPR Screen for Prevention of Synapse Loss in Alzheimer’s Disease
Laura Beth McIntire, Ph.D.
Columbia University Medical Center
New York, New York
2016 New Investigator Research Grant
Can a new gene modifying method help identify novel factors that protect nerve cells from the effects of beta-amyloid?
Nerve cells in the brain communicate with one another using specialized structures called synapses, which send chemical messages across tiny channels between cells. During Alzheimer’s disease, beta-amyloid protein fragments are thought to accumulate in the brain and contribute to the damage or loss of synapses. This can hinder the nerve cells’ ability to communicate and may contribute to cognitive decline.
Phosphoinositides (PIs) are molecules important for nerve cell function and recent research suggests that certain modifications to PIs may help prevent synapse loss caused by beta-amyloid. PIs can be modified in several ways with the help of specific proteins found in nerve cells called PI-modifying enzymes. People with Alzheimer’s disease may have decreased levels of these modifying proteins in their brains, which could compromise their ability to combat synapse loss caused by beta-amyloid.
Laura Beth McIntire, Ph.D. and colleagues will use a cutting-edge method called a CRISPR screen to identify genes that are important for the production of PI-modifying enzymes that help prevent synapse loss. The team will perform their experiments using a type of nerve cells grown in laboratory dishes that produce and mimic nerve cell synapses more closely than previous models. The researchers hope to identify new genes and the molecules they produce that alter the levels of PIs in nerve cells and determine how these molecules could be used to protect synapses from the toxic effects of beta-amyloid.
These efforts may help advance a new laboratory method for identifying genes that mediate the effects of beta-amyloid on nerve cell synapses. The results of these studies could also provide a better understanding of the molecular mechanisms underlying the protective effects of PIs and how these mechanisms may be targeted to preserve nerve cell communication in people with Alzheimer’s disease.