|Department of Cell & Systems Biology
University of Toronto
25 Harbord St.
Toronto, ON M5S 3G5
Bioinformatics & Computational Biology
|A major goal of our lab is to better understand the role of post-transcriptional gene regulation in the development, differentiation, and function of the nervous system. The nervous system provides an attractive model to study the mechanism and role of cell-type specific gene regulation because it is composed of diverse neuronal cells that require customized regulatory programs to achieve specialized functions. One research area in my group will focus on understanding the mechanisms and function of alternative splicing in the developing and mature nervous system using both mammalian stem cells and C. elegans. Through the process of alternative splicing, multiple messenger RNAs can be generated from single precursor transcripts. The evolution of alternative splicing has greatly contributed to the diversification of metazoan transcriptomes, and in some species can generate up to an order of magnitude greater number of transcript isoforms than the corresponding repertoire of protein-coding genes. We pursue these problems using a combination of biochemistry, cell biology, molecular genetics, and genome-wide analyses. Additionally, several ongoing projects are directing our research towards investigating the role of other layers of co- and post-transcriptional gene regulation in nervous system development and function.|
Alternative Splicing: C. elegans as a Model System. Gracida, Xicotencatl, Adam D Norris, and John A Calarco. 2016. Regulation of Tissue-Specific Advances in experimental medicine and biology. doi:10.1007/978-3-319-29073-7_10. http://www.ncbi.nlm.nih.gov/pubmed/27256389.
Creating Genome Modifications in C. elegans Using the CRISPR/Cas9 System. Calarco, John A, and Ari E Friedland. 2015. Methods in molecular biology (Clifton, N.J.). doi:10.1007/978-1-4939-2842-2_6. http://www.ncbi.nlm.nih.gov/pubmed/26423968.
Efficient Genome Editing in Caenorhabditis elegans with a Toolkit of Dual-Marker Selection Cassettes. Norris, Adam D, Hyun-Min Kim, Mónica P Colaiácovo, and John A Calarco. 2015. Genetics, no. 2 (July 30). doi:10.1534/genetics.115.180679. http://www.ncbi.nlm.nih.gov/pubmed/26232410.
A pair of RNA-binding proteins controls networks of splicing events contributing to specialization of neural cell types. Norris, Adam D, Shangbang Gao, Megan L Norris, Debashish Ray, Arun K Ramani, Andrew G Fraser, Quaid Morris, Timothy R Hughes, Mei Zhen, and John A Calarco. 2014. Molecular cell, no. 6 (June 5). doi:10.1016/j.molcel.2014.05.004.http://www.ncbi.nlm.nih.gov/pubmed/24910101.
EOL-1, the homolog of the mammalian Dom3Z, regulates olfactory learning in C. elegans. Shen, Yu, Jiangwen Zhang, John A Calarco, and Yun Zhang. 2014. The Journal of neuroscience : the official journal of the Society for Neuroscience, no. 40 ( 1). doi:10.1523/JNEUROSCI.0230-14.2014. http://www.ncbi.nlm.nih.gov/pubmed/25274815.
Heritable genome editing in C. elegans via a CRISPR-Cas9 system Friedland, Ari E, Yonatan B Tzur, Kevin M Esvelt, Monica P Colaiácovo, George M Church, and John A Calarco. 2013..Nature methods, no. 8 (June 30). doi:10.1038/nmeth.2532. http://www.ncbi.nlm.nih.gov/pubmed/23817069.
Heritable custom genomic modifications in Caenorhabditis elegans via a CRISPR-Cas9 system. Tzur, Yonatan B, Ari E Friedland, Saravanapriah Nadarajan, George M Church, John A Calarco, and Monica P Colaiácovo. 2013. Genetics, no. 3 (August 26). doi:10.1534/genetics.113.156075. http://www.ncbi.nlm.nih.gov/pubmed/23979579.
“Cryptic” exons reveal some of their secrets. Calarco, John A. 2013. eLife (January 22). doi:10.7554/eLife.00476. http://www.ncbi.nlm.nih.gov/pubmed/23358458.
Emerging Roles of Alternative Pre-mRNA Splicing Regulation in Neuronal Development and Function. Norris, Adam D, and John A Calarco. 2012. Frontiers in neuroscience (August 21). doi:10.3389/fnins.2012.00122. http://www.ncbi.nlm.nih.gov/pubmed/22936897.