Professor Ben Blencowe

By Meaghan Sullivan

Ben Blencowe is Professor of Molecular Genetics, the Banbury Chair in Medical Research, and Director of the Donnelly Sequencing Centre at the University of Toronto. He has received numerous awards and honors, including election as a Fellow of the Royal Society of Canada and the Royal Society of London. Throughout his career, he has mentored over 50 trainees and has helped launch budding scientists into careers both inside and outside of academia, including fifteen principal investigators.

Prof. Blencowe studied microbiology and molecular biology and obtained his BSc degree at Imperial College London in 1988. While an undergraduate, he says that Prof. Jean Beggs’ lectures “cemented my initial interest in splicing.” By reading work from the laboratories of Profs. Phillip Sharp and Joan Steitz, Blencowe became fascinated by this process. His attention later turned to alternative splicing, “in part through the realization that species with vastly different degrees of biological complexity have comparable numbers of protein-coding genes.” Prof. Blencowe trained with Prof. Angus Lamond at the EMBL during his PhD, and with Prof. Phillip Sharp at the Massachusetts Institute of Technology as a post-doc. In his PhD, he sought to describe interactions that are integral to the structure and function of the snRNPs in the splicing interaction. Later, in work initiated in the Sharp laboratory, he discovered and characterized a new class of SR-related proteins.

Prof. Blencowe started his lab in 1998 working on splicing enhancers and coactivators, while also realizing the power of microarrays to study splicing on a genome-wide scale. He saw that developing a system for high-throughput profiling of alternative splicing would provide valuable insights, but he needed to convince grant reviewers that it was worthwhile. He ended up “borrowing funds from grants intended for other projects to develop a microarray-based platform affording the quantitative profiling of alternative splicing in mammalian cells.” This system opened up global-scale insights into splicing regulation. He says, “Once this method worked, securing funds to support work in this area was no longer an issue.” Since then, his group has continued to develop and apply genome-wide approaches to discover and functionally characterize programs of alternative splicing, including those with critical roles in the regulation of stem cell pluripotency and nervous system development.

Focus on important research questions you are passionate about. Try to avoid busy areas, unless you have a novel angle.”

Currently, Prof. Blencowe is most excited to understand the “links between neuronal microexon misregulation and neurological disorders.” This interest stems from previous work from his group revealing a conserved program of neuronal microexons that is frequently disrupted in the brains of autistic individuals. Most recently, Dr. Thomas Gonatopoulos-Pournatzis, a talented post-doc in Blencowe’s lab (who is now starting his own group at the NIH), demonstrated that deletion of a neuronal microexon in the translation initiation factor eIF4G1 leads to molecular and phenotypic outcomes related to those seen in Fragile X syndrome. Prof. Blencowe sees a route to potential therapeutic intervention in neurological disorders through “pharmacological modulation of the neuronal microexon regulatory network.”

His key piece of advice for trainees is to “focus on important research questions you are passionate about. Try to avoid busy areas, unless you have a novel angle.” From his own mentors, he learned “to be persistent in pursuing big picture questions,” and took advantage of the freedom and independence they provided to pursue his research interests.

Throughout his time in the RNA Society, Prof. Blencowe has seen it play “a major role in fostering a wonderful community spirit among researchers in the field.” While he views the annual meetings as an “outstanding forum for catching up with the latest in the field,” he is also appreciative of the opportunities they provide trainees to “gain exposure” that is “critical for their career development.” In line with his passion for research, Blencowe said his favorite scientific stories from the past several RNA meetings include the beautiful spliceosome structures from Profs. Reinhard Lührmann, Kiyoshi Nagai, and Yigong Shi, and work on the development of Spinraza to treat SMA by Prof. Adrian Krainer and colleagues.

Blencowe’s lab has an active Twitter account: @Blencowe_Lab. He doesn’t have a particular favorite RNA because “RNA’s appeal is in its diversity!”