Seelig Lab
Principal Investigator: Georg Seelig
Institution: University of Washington (Seattle, WA)
Primary Subfield: Molecular & Cell Bio
Recruitment Status: Inquire for rotation/fellowship opportunities
Research Focus
PROJECT SUMMARY Alternative splicing (AS) is a major driver of protein isoform diversity and is regulated in a highly cell type-specific manner. A better understanding of the cell type-specific splicing code will not only provide novel insights into the role of alternative splicing in disease and development but will also result in novel genetic tools for perturbing and interrogating cell types of interest. Synthetic splicing constructs have been successfully used to target activation of reporter and therapeutic genes to cancer cells carrying mutations in splice factors or to make gene therapies conditional on a small molecular trigger. Existing examples highlight the potential of AS as a programmable control mechanism but do not provide a clear path towards engineering splice regulatory sequences that can be used to target gene expression to any desired cell type or state. Here, we propose to combine synthetic biology with machine learning to generate highly cell type-specific splicing constructs. Building on our earlier work, we will first quantify cell type-specific AS using splicing massively parallel reporter assays (MPRAs). We will focus on exon skipping and intron retention…
Active NIH Awards
- 5R01GM149631-04: Engineering cell type-specific splicing regulation (2026)
- 5R33CA286947-02: Sequence optimization for mRNA cancer therapy (2026)
- 5R01GM149631-03: Engineering cell type-specific splicing regulation (2025)
- 1R33CA286947-01A1: Sequence optimization for mRNA cancer therapy (2025)
- 5R01GM149631-02: Engineering cell type-specific splicing regulation (2024)
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