Microexons: at the nexus of nervous system development, behaviour and autism spectrum disorder.
Our latest review paper is out in Current Opinion in Genetics & Development.
Kenny Rebelo is awarded the Cecil Yip Doctoral Research Award.
Shaghayegh Farhangmehr is awarded an Ontario Graduate Scholarship.
Thomas Gonatopoulos-Pournatzis accepts a prestigious Investigator position in the RNA Laboratory of the Center for Cancer Research at NIH, and will open his lab later this year.
Systematic multi-site genomic editing using a hybrid CRISPR-Cas platform reveals gene paralog interactions and essential alternative exons.
Our most recent paper (involving a collaboration with Jason Moffat, Chad Myers and colleagues), describes a new functional genomics tool enabling the systematic mapping of genetic interactions and interrogation of the functions of sizable genomic segments in mammalian cells. Named ‘Cas Hybrid for Multiplexed Editing and screening Applications’ (CHyMErA), it outperforms genetic screens using Cas9 or Cas12a editing alone. Application of CHyMErA to the ablation of mammalian paralog gene pairs revealed extensive genetic interactions and uncovered phenotypes normally masked by functional redundancy. Application of CHyMErA in a chemogenetic interaction screen identified genes that impact cell growth in response to mTOR pathway inhibition. Moreover, by systematically targeting thousands of alternative splicing events, CHyMErA identified exons underlying human cell line fitness. CHyMErA thus represents an effective screening approach for genetic interaction mapping and the functional analysis of sizable genomic regions, such as alternative exons.
Justin Lim is awarded an NSERC Alexander Graham Bell Canada Doctoral Graduate Scholarship.
Autism-misregulated eIF4G microexons control synaptic translation and higher-order cognitive functions.
In this paper, which arose through a collaboration with Sabine Cordes and several additional groups in Toronto, we characterized vertebrate-conserved neuronal microexons in the translation initiation factor eIF4G1 and eIF4G3 paralogs, which are regulated by SRRM4 and neuronal activity, and misregulated in autistic brains. Genetic ablation of these proteins results in increased expression of numerous proteins that impact synaptic transmission and plasticity. Mice deficient of the Eif4g1 microexon display altered social behavior and memory deficits, accompanied by an aberrant form of protein synthesis-dependent synaptic plasticity. The eIF4G microexons primarily regulate neuronal translation by promoting ribosome stalling, through a mechanism associated with the increased coalescence of numerous neuronal granule components, including the Fragile X mental retardation protein, FMRP. Mechanistic similarities by which the eIF4G microexons and FMRP control translation of synaptic protein expression provide an intriguing link between idiopathic cases of autism, in which pronounced eIF4G1 microexon skipping is often detected, and Fragile X syndrome. This work further suggests a novel potential therapeutic strategy for neurological disorders.
Zheng Luo is awarded the CH Best Postdoctoral Fellowship.
Alternative splicing regulatory networks: Functions, mechanisms, and evolution.
Latest review article on alternative splicing written with Jernej Ule at the Crick Institute.
Ben is elected Fellow of the Royal Society of London (UK).
Drice Challal is awarded an EMBO Postdoctoral Fellowship.
Autism spectrum disorder: insights into convergent mechanisms from transcriptomics.
Our latest review featured on the cover of Nature Reviews in Genetics.
Efficient and accurate quantitative profiling of alternative splicing patterns of any complexity on a laptop.
Our latest paper describes a powerful new method for analyzing alternative splicing using RNA-Seq data.
Rasim Barutcu is awarded a Banting Postdoctoral Fellowship.
Please don't hesitate to contact us to learn more about the work in our lab.
The Donnelly Centre
University of Toronto
160 College St, Rm 1030
Toronto, ON M5S 3E1
Ben: b -dot- blencowe -at- utoronto -dot- ca
Lab Manager: jonathan -dot- ellis -at- utoronto -dot- ca