CRISPR, MPRA, and the genetics of mental health

Some genetic variants may help explain why different psychiatric disorders share overlapping biology.

In this episode of Speaking of Mol Bio, host Steve Lewis speaks with Jess McAfee, PhD, and Alejandro Gomez from the University of North Carolina at Chapel Hill about their work studying pleiotropic variants associated with psychiatric disorders. Jess explains how genome-wide association studies can identify regions of the genome linked to disease risk, but often cannot pinpoint which specific variants are functionally important. Her work used massively parallel reporter assays, or MPRAs, to test whether different alleles in non-coding regulatory regions alter gene expression. Alejandro then describes how CRISPRi can help take the next step by targeting those variants in the genome and asking which nearby genes respond. Together, these approaches provide a clearer path from statistical genetic association to functional biological insight.

The episode also highlights two early-career scientists whose paths into molecular biology were anything but linear. Jess moved from plant genetics to human genomics, while Alejandro shifted from chemistry and industry into CRISPR-based neuroscience research. Along the way, they reflect on mentorship, lab culture, persistence, AI, and the excitement of working with technologies that are still rapidly evolving.

NOTE: This episode may contain general information relating to various medical conditions or their treatment. This information is provided for informational purposes only and is not meant to be a substitute for advice provided by a doctor or other qualified health care professional. Patients should always consult with a doctor or other health care professional for medical advice or information about diagnosis and treatment.

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