Using Human Models of SynGAP1
Here are our introductory comments:
Intro for Dr. Marcelo Pablo Coba (November 5, 2020)
We are very excited to continue the SRF webinar series. The goals of the series are:
- getting you closer to the science
- making you aware of the research that is been done and the opportunities to participate
- and empowering your communications with clinicians
We also want to remind you of our next webinar in the series with Dr. Stephan Sanders on “SYNGAP1 in the Developing Human Cortex” tomorrow Friday, November 6th at 9 AM Pacific. Dr. Sanders has been invaluable in developing frameworks for identifying autism risk genes as well as the mechanisms by which mutations in these genes cause disruption to developmental pathways.
Today’s talk is “How & why to use human cellular models to study Syngap1” by Dr. Marcelo Pablo Coba. Dr. Coba, is an associate professor of psychiatry and behavioral science at the University of Southern California’s (USC) Keck School of Medicine. Dr. Coba’s impressive educational background includes a Doctor of Pharmacy and postdoctoral work in Neuroscience. His education sets him apart and aligns well with SynGAP patients’ needs.
Dr. Coba has a long-standing interest in the role of proteins like SYNGAP1 that are important in the synaptic function, synaptic plasticity, learning and memory. He wants to help us understand the molecular and cellular changes that occur in our Syngapians. Professor Coba proposed a plan to address this essential and complicated question. The proposed work includes ground-breaking new ways to describe the effects of known pathogenic SynGAP1 variants in neuronal cells, and is critical to finding molecular targets for potential medications.
Dr. Coba has a close working relationship with SRF, and has been generous sharing his ideas and listening to parents. For several years Dr. Coba has been working on SynGAP1 Encephalopathy. Now he is asking the Syngap Research Fund to support his work. He is optimistic this will eventually lead to better outcomes in translational research.
We as a group feel privileged and lucky to have Dr. Coba working with us and we are thrilled to support his work.
Dr. Marcelo Coba is a psychiatric researcher at the USC School of Medicine. To begin the webinar, Dr. Coba gives background on research using human models as well as on the synapse and postsynaptic density (PSD). He talks about how SynGAP doesn’t work alone, but it works in the context of the surrounding molecules in PSD. He specifically talks about how the RASGAP region of SynGAP interacts with RAS and GAP regions of other proteins, creating a set of components that can be regulated in the synapse. Mutations in these “synaptic” proteins are associated with a number of neurodevelopmental disorders. Dr. Coba then talks about NGN2 neurons-spines morphology, the process of using immature neurons to develop spines so he can study PSD and SynGAP. Through his research, he has found that different mutations in the SynGAP gene can cause completely opposite phenotypes. He closes by talking about work to be done in the future in order to better characterize what each mutation is doing to the SynGAP protein.