School of Biomedical Sciences is pleased to invite you to join the following seminar:

Date: 27 November 2023 (Monday)
Time: 4:00 pm – 5:00 pm
Venue: Lecture Theatre 3, G/F, William M.W. Mong Block, 21 Sassoon Road

Speaker: Professor Didier Stainier, Director, Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research
Talk Title: Transcriptional adaptation, a newly discovered mode of genetic compensation

Host: Professor Kathryn Cheah

Biography

Didier Stainier is the director of the Department of Developmental Genetics at the Max Planck Institute for Heart and Lung Research, Bad Nauheim (Frankfurt), Germany.  He studied Biology in Wales, Belgium and the USA (Brandeis University) where he got a BA in 1984.  He then received his Ph.D. in Biochemistry and Biophysics from Harvard University (1990) where he investigated the cellular basis of axon guidance and target recognition in the developing mouse brain with Wally Gilbert.  After a Helen Hay Whitney postdoctoral fellowship with Mark Fishman at the Massachusetts General Hospital (Boston) where he initiated the studies on zebrafish cardiac development, he set up his lab at the University of California San Francisco in 1995, where he expanded his research to investigate questions of cell differentiation, tissue morphogenesis, organ homeostasis and function, as well as organ regeneration, in the zebrafish cardiovascular system and endodermal organs.  In 2012, he moved to the Max Planck Institute where his laboratory continues to utilize genetic approaches to investigate cellular and molecular mechanisms of developmental and regenerative processes in both zebrafish and mouse.  More recently, his group has also started studying mechanisms of genetic compensation in a number of model systems including zebrafish, mouse, C. elegans, and Neurospora.

Abstract
Each human genome has been reported to contain approximately 100 loss-of-function variants, with roughly 20 genes completely inactivated.  Some of these completely inactivated genes are essential genes, and yet they are present in a homozygous state in apparently healthy individuals.  This totally unexpected lack of phenotype has also been observed in commonly studied model organisms from yeast to mammals.  Various hypotheses have been proposed to explain these findings including Genetic Compensation (GC).  GC manifests itself as altered gene/protein expression, or function, which leads to a wild-type-like phenotype in homozygous mutant or heterozygous individuals who would be predicted to exhibit clear defects.  Traditionally, GC has been thought to involve protein feedback loops such that if one component of a regulatory pathway is deficient, a compensatory rewiring within a network or the activation of a functionally redundant gene occurs.  However, not every major regulatory network has evolved to incorporate such complex features.  Another mechanism of GC is the newly identified process of Transcriptional Adaptation (TA): some deleterious mutations, but not all, trigger the transcriptional modulation of so-called adapting genes.  Depending on the nature of the modulated genes, GC can occur.  Notably, unlike other mechanisms underlying genetic robustness, TA is not triggered by the loss of protein function.

We discovered TA while trying to understand the phenotypic differences between knockout (mutant) and knockdown (morphant) zebrafish embryos.  Further studies identified additional examples of TA in zebrafish as well as examples in C. elegans and in mammalian cell lines.  By generating and analyzing several mutant alleles for these genes, including non-transcribing alleles, we found that the mutant mRNA is required to trigger TA.  Based on these and other data, we hypothesize that all mutations that cause mutant mRNA degradation can trigger TA.  This presentation will go over our published and unpublished data on TA in several model systems.

ALL ARE WELCOME

Should you have any enquiries, please feel free to contact Miss Angela Wong at 3917 9216.