Lin Lab
Principal Investigator: Michael Z. Lin
Institution: Stanford University (Stanford, CA)
Primary Subfield: Neuroscience
Recruitment Status: ✅ Accepting PhD Students ✅ Hiring Postdocs
Research Focus
ABSTRACT The ability to rapidly induce fully active proteins of interest (POIs) upon drug administration anywhere in the body would be widely useful for developmental biology, synthetic biology, and gene and cell therapies, but existing drug-regulated protein activation methods have limitations in speed, dynamic range, generalizability across proteins, and applicability across tissues. The overall goal of this proposal is to overcome these limitations by developing a novel approach, named Split Protein Ligation Activated by Steroid Hormone (SPLASH), focusing on achieving lower background, faster induction, and plug-and-play generalizability for diverse POIs. The innovative design of SPLASH involves sequestering an intein-extein fusion with the T2 mutant of the estrogen receptor hormone-binding domain (ERT2), so that 4-hydroxytamoxifen (4-OHT) can release it to trans- spice with a complementing intein-extein fusion, resulting in the production of any POI. As an example, SPLASH will be applied to improve the Cre recombinase, addressing issues of leakiness and low induced activity. This work will leverage recent atomic-level understsanding of the steps in steroid hormone receptor sequ…
Active NIH Awards
- 5R21GM157668-02: Ready, set, then go: Rapid posttranslational induction of protein production by drug administration in vivo (2026)
- 1R01NS142873-01A1: Ultrasound-Controlled in Vivo Gene Editing with Photoswitchable CRISPR-CasMINI (2026)
- 1R21GM157668-01: Ready, set, then go: Rapid posttranslational induction of protein production by drug administration in vivo (2025)
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