Pinpointing How Autism Affects the Brain

Led by Dr. Stephen E.P. Smith, the SEPS Lab is working to uncover what the gene variations that contribute to autism have in common, opening the door to a new generation of potential treatments.

Studying a key synapse

Researchers have linked more than 100 gene mutations to autism. But it’s rare to find two children with autism who have the same mutation. This suggests that autism is not a single disease – it’s hundreds of rare, genetic diseases that cause similar symptoms.

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We are looking for similarities in how these diseases affect the brain and change how it functions. Our current research focuses on the brain’s synapses, which make important calculations and help control how the brain and body function.

Each synapse contains a complex web of proteins that work together like tiny molecular machines. Many of the gene mutations linked to autism affect how these protein machines are built. We suspect this might explain why the brains of children with autism function differently than typical children’s brains.

To explore this possibility, we developed an innovative system – called quantitative multiplex immunoprecipitation – that maps out how proteins interact with each other in a synapse. We are using this system to pinpoint how different mutations affect the protein machinery at the glutamate synapse, which is where the brain processes and stores information.

This could help us understand which mutations cause the synapse to malfunction, affecting how children speak, play or interact socially. It could also help us identify when different gene mutations have similar effects on the synapse and how it process information.

Tailored autism treatments

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Our long-term goal is to be able to group children with autism into categories based on how their gene mutations affect brain function. This would enable a more precise understanding of how autism varies among children. And it would open the door to new treatments that are tailored to different types of autism.

Learn more

Please visit our University of Washington lab page for more details on our research.

“Our vision is to categorize different types of autism so we can sequence patients’ genes and say ‘you have type two autism and we know which treatments work best compared to type one or type three’.”

– Dr. Stephen E.P. Smith

Postdoctoral Position Available Studying the Molecular Biology of the Synapse

The SEPS Lab invites applications for a postdoctoral position. Work in the SEPS lab focuses on shared molecular pathology among the many genetic causes of autism. We use a unique analysis platform, quantitative multiplex immunoprecipitation (QMI), to measure a network of protein-protein interactions at the glutamate synapse. This network acutely changes in response to neuronal activity or glutamate receptor agonists/antagonists, and may represent a neuronal signal transduction network. Our lab is characterizing network behavior in mouse and human iPS models of autism in order to better understand and potentially treat the disorder.

The successful candidate will perform both exacting bench work to implement the QMI assay, and advanced statistical and bioinformatics analyses on the resulting high-dimensional datasets using MatLab and R. The candidate will work closely with a technician and graduate/undergraduate students to plan and supervise several parallel lines of investigation involving primary neuronal cell culture, genetic mouse models, and human iPS cells. The candidate will be expected to independently move projects forward, write papers, and apply for F32 or equivalent grants.

The ideal candidate will have the ability to perform precise wetlab work and complex bioinformatics analyses. Prior experience with human iPS cell culture and MatLab or R programming would be beneficial. Creative, big-picture thinking and dedication to autism research are essential.

The selected candidate will join the vibrant research community at CIBR, located on the top floor of a newly renovated building in downtown Seattle. A modern, open lab space, a collegial atmosphere, on-site gym and rooftop garden, and top-of-the-line equipment, office space and meeting rooms make this an ideal training environment. Initial appointment will be for one year, with extension contingent on funding and performance.

Learn more and apply

Investigator Biography

Dr. Stephen E.P. Smith is a principal investigator at the Center for Integrative Brain Research and an assistant professor at the University of Washington School of Medicine. 

Please visit Smith’s Google Scholar page to see a list of his publications.