Glycosylation in Neurobiology

Ion channel dysfunction is associated with over 60 different channelopathy diseases including epilepsy, paralysis, ataxia, deafness, memory and learning loss, cardiac arrhythmias, and cancer. Thus, the need to understand causes of ion channel dysfunction and methods to treat channelopathies represents an increasingly important international health objective.

Brains are formed by the cooperative interactions of many individual neurons. If the environment surrounding these neurons is altered, this can alter the way in which the neurons cooperate and the brain may not function properly or develop correctly (See wild type and mutant mushroom body from fly brain in Fig. 1). The goal of this NSF Emerging Frontiers in Research and Innovation project is to understand how the extracellular environment affects individual ion channels, action potentials, and neuronal cell behavior. We will use this knowledge to decipher the ultimate impact on multicellular systems such as the brain. We are initially attempting to understand this relationship in the model fruit fly organism (Drosophila), so that we may one day be able to alleviate disorders of the human brain and nervous system.

This project creates a new interdisciplinary network of researchers with expertise in molecular ion channel modeling; neuronal kinetic modeling, electrophysiology, biochemical engineering, and Drosophila genetics in order to investigate the role that the biochemical environment, and in particular glycosylation and sialic acid, plays on electrical properties and function of ion channels, neuronal processes, and neurological disease.

Sialic acid is the first juncture between the cell and its surroundings. Combining computation and experimentation, this study will investigate how changes in a cell’s sialic acid environment are related to changes in the cell’s ion channels—how it allows some electric signals to pass through and not others—and in turn how these changes may lead to neurological defects. This work aims to develop a fundamental understanding for the treatment of brain diseases, such as epilepsy and memory and learning loss, at the molecular level.

More information: http://nsf.gov/news/news_summ.jsp?cntn_id=109948&org=olpa&from=news