Robotic microinjection enables large-scale transgenic studies of Caenorhabditis elegans
The nematode Caenorhabditis elegans is widely employed as a model organism to study basic biological mechanisms. However, transgenic C. elegans are generated by manual injection, which remains low-throughput and labor-intensive, limiting the scope of approaches benefitting from large-scale transgenesis. Here, we report a robotic microinjection system, integrating a microfluidic device capable of reliable worm immobilization, transfer, and rotation, for high-speed injection of C. elegans. The robotic system provides an injection speed 2-3 times faster than that of experts with 7-22 years of experience while maintaining comparable injection quality and only limited trials needed by users to become proficient. We further employ our system in a large-scale reverse genetic screen using multiplexed alternative splicing reporters, and find that the TDP-1 RNA-binding protein regulates alternative splicing of zoo-1 mRNA, which encodes variants of the zonula occludens tight junction proteins. With its high speed, high accuracy, and high efficiency in worm injection, this robotic system shows great potential for high-throughput transgenic studies of C. elegans.
Authors
- Hua Tang (ORCID: https://orcid.org/0000-0002-5757-4123)
- Shaojia Wang (ORCID: https://orcid.org/0000-0001-9347-9695)
- Peng Pan (ORCID: https://orcid.org/0000-0003-0096-6801)
- Rui Zuo (ORCID: https://orcid.org/0000-0003-4464-3078)
- Xinyu Liu (ORCID: https://orcid.org/0000-0001-5705-9765)
- Ang Li (ORCID: https://orcid.org/0000-0002-6431-9796)
- Pengsong Zhang (ORCID: https://orcid.org/0000-0001-8714-3562)
- Ryan Li (ORCID: https://orcid.org/0000-0001-9750-9361)
- W. Brent Derry (ORCID: https://orcid.org/0000-0002-1977-8475)
- Pallavi P. Pilaka-Akella
- Kailynn MacGillivray (ORCID: https://orcid.org/0009-0009-2068-0481)
- Zhen Qin
- John A. Calarco (ORCID: https://orcid.org/0000-0002-2197-7801)
- Mei Zhen (ORCID: https://orcid.org/0000-0003-0086-9622)
- Charlotte Martin (ORCID: https://orcid.org/0000-0001-5488-9675)
- Sanjana Bhatnagar
- Arneet L. Saltzman (ORCID: https://orcid.org/0000-0002-5827-3322)
- Wesley Hung (ORCID: https://orcid.org/0000-0001-8488-7638)
- Chengyin Li (ORCID: https://orcid.org/0000-0001-8543-3419)
- Pengfei Xu (ORCID: https://orcid.org/0000-0003-3414-4662)
- William Sun (ORCID: https://orcid.org/0000-0003-3279-7408)
- Karinna Pe
- Bin Yu (ORCID: https://orcid.org/0000-0002-3747-8935)
- Zefang Zhang (ORCID: https://orcid.org/0009-0004-6358-838X)
- Sharanja Premachandran
- Michael Zoberman
Institutions
- Mount Sinai Hospital (CA)
- University of Toronto (CA)
- Lunenfeld-Tanenbaum Research Institute (CA)
- Toronto Rehabilitation Institute (CA)
- Hospital for Sick Children (CA)
- McGill University (CA)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-14
- DOI
- https://doi.org/10.1038/s41467-024-53108-5
- Citations
- 17
- Primary Topic
- Genetics, Aging, and Longevity in Model Organisms
- Type
- article
- Field-Weighted Citation Impact
- 3.87
Funders
- Canada Foundation for Innovation
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada