Seminar Poster

Speaker:
Dr. Colin Crist
Associate Professor
Department of Human Genetics
McGill University
Montreal, Canada

About the Speaker:
Dr. Colin Crist received his BSc from the University of British Columbia and his PhD from the University of Tokyo, where he investigated the biology of ‘prion’ domains found in translation termination factors of budding yeast. As a post-doctoral research associate in the laboratory of Dr. Margaret Buckingham at the Institut Pasteur (Paris, France), he studied the role of the microRNA pathway in skeletal muscle development and regeneration. He is an associate professor in the Department of Human Genetics at McGill University, and he holds the Marjorie and Gerald Bronfman Chair in Stem Cell Research. He is a principal investigator at the Lady Davis Institute for Medical Research at the Jewish General Hospital.

Dr. Crist’s laboratory studies molecular mechanisms underlying muscle development, regeneration and disease. Our recent focus has been on the role of microRNAs, RNA binding proteins and pathways that regulate global protein synthesis to maintain muscle stem cells quiescent, but primed to rapidly activate the myogenic program in response to skeletal muscle injury.

Abstract:
Regeneration of adult tissues depends on somatic stem cells that remain quiescent, yet are primed to enter a differentiation program. The molecular pathways that prevent activation of these cells are not well understood. In mouse skeletal muscle, these features are reconciled by multiple translational control mechanisms mediated by microRNA and RNA binding proteins that ensure primed muscle stem cells (MuSCs) are not activated. We show that a general repression of translation, mediated by the phosphorylation of translation initiation factor eIF2a at serine 51 (P-eIF2α), is also required to maintain the quiescent state. Skeletal muscle stem cells unable to phosphorylate eIF2a exit quiescence, activate the myogenic program and differentiate, but do not self-renew. Pharmacological inhibition of eIF2a dephosphorylation permits ex vivo expansion of MuSCs that retain regenerative capacity after engraftment into the mdx mouse model of Duchenne muscular dystrophy. We propose a model whereby P-eIF2α ensures in part the robust translational silencing of accumulating mRNAs that is needed to prevent the activation of muscle stem cells and, on the other hand, the selective translation of specific mRNAs that contribute to the molecular signature of MuSC stemness.

CME Accreditation:

* One CME point for attendance approved by the Medical Council of Hong Kong (MCHK). [ Activity No. 3594 ]

All are welcome.
For enquiries, please contact Mr Jonathan Lee at 3763 6088.