(694g) Integrative Approaches to Elucidate Mechanisms of Neurological Disorders

Over 30 million people worldwide are living with Alzheimer’s disease (AD) and over 45 million people worldwide are estimated to be living with Autism Spectrum Disorders (ASD). The prevalence of both neurological disorders has increased sharply in recent years, having significant negative impact on quality of life and economic burden. Gaps in our understanding of the molecular mechanisms that underlie AD and ASD have exacerbated difficulties in developing effective treatments. In each disorder, dysregulations at the points of neuronal cell connections (synapses) play a critical role. As AD progresses with age, the number and density of synapses in critical brain regions is reduced. At critical developmental timepoints early in life (prior to age 2), synaptic connections are not properly pruned leading to imbalances in excitatory and inhibitory inputs. Our research combines experimental and computational approaches to study the underlying mechanisms of protein translation and signal transduction in synapses. Using multiscale computational approaches we are investigating the role of macromolecular complexes in the timing and spatial dependencies of protein network signaling in synapses. Using novel protein labeling techniques combined with proteomics and high resolution imaging we are investigating the role of protein translation and subcellular localization in synaptic processes. These investigations are generating new insights into the molecular mechanisms underlying the role of tau protein in Alzheimer’s disease and the role of scaffolding proteins in Autism Spectrum Disorders.