Gemma Carvill
Northwestern University, IL·Genetics
Cells sometimes include short stretches of a gene, called poison exons, that deliberately mark the gene's message for destruction. When a poison exon is spliced into the messenger RNA, it adds an early stop signal.
- Fields
Genetics
Neuroscience
- Topics
poison exons
alternative splicing
nonsense-mediated decay
- Grants
- 1 known grant, through May 2029
What they work on
- Identify the RNA-binding proteins that cause extra splicing-in of an SCN1A poison exon in people with epilepsy, using splice reporters and proteomics, and test whether antisense oligonucleotides correct it in patient iPSC-derived neurons.
- Map poison exon use in each cell type across brain development with MAS-ISO-seq long-read single-cell sequencing and deep short-read sequencing, including cycloheximide-treated cells in which RNA decay is blocked.
- Use machine learning to define the genomic features of poison exons, then search public genome data from people with neurodevelopmental disorders for variants that disrupt their splicing, and release a webtool.
More about the research
The cell then destroys that RNA through a quality-control process called nonsense-mediated decay. Brain cells switch poison exons on and off as the brain develops. Genetic variants that disrupt this switching have been linked to epilepsy, malformations of the brain's cortex and a childhood neurodegenerative disorder. Antisense oligonucleotides (ASOs), short pieces of synthetic genetic material that change how RNA is spliced, already target poison exons in clinical trials for rare epilepsies. Still, it is unclear how variants cause wrong splicing, which poison exons are used in the brain, and what genomic features define them.
Why it matters
Many children with epilepsy and other neurodevelopmental disorders never receive a genetic diagnosis. Finding variants that disrupt poison exon splicing could explain some of these cases. It could also reveal new targets for antisense oligonucleotide therapies like those already in trials for rare genetic epilepsies, and a shared webtool could help clinicians and researchers interpret such variants.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
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The school
Northwestern University: 71 labs on PI Pages, $1.3B a year on research, 536 research doctorates a year.
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