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Prof. Karuna Sampath (University of Warwick)

Coordinate Regulation of Development by RNA Control Elements

The LSI is the scientific home for an integrated team of researchers with complementary expertise, creating a dynamic and inspiring hub for disease-related research. This seminar series embodies our commitment to excellence in interdisciplinary research and clear communication. The speakers research in fields ranging from mathematics to evolution, from biophysics to clinical medicine, while addressing all researchers with their equally broad backgrounds. Our goal is to dissolve boundaries and spark engaging conversation in an informal setting.


Event details

Abstract

Developmental gene expression is regulated at multiple levels. We find that an RNA element we previously identified in the zebrafish nodal /squint (sqt) 3’UTR is shared by many Nodal signalling pathway components: the Nodal ligands, its inhibitors, receptor and intracellular effector RNAs. Reporter assays for localization and translation in early zebrafish embryos suggest that the RNA elements function similarly to regulate these transcripts. An RNA-binding protein, Y-box binding protein1 (Ybx1), binds to the RNA element and the translation pre-initiation complex, resulting in translational repression of nodal ligand and lefty inhibitor. Zebrafish ybx1 mutant embryos show premature Nodal and Lefty translation and deregulated Nodal signalling. Thus, multiple components of the same developmental signalling pathway are translationally regulated by a shared RBP/RNA element “regulon". This module also regulates human NODAL. By computational analysis we identified >800 zebrafish transcripts harbouring similar elements, which we are currently assaying for in vivo activity in zebrafish embryos.  Our preliminary findings indicate broader roles for this regulon and in a variety of processes.

Prof. Karuna Sampath (University of Warwick)

Coordinate Regulation of Development by RNA Control Elements

Dr. Sampath is a leading developmental biologist working at the Centre for Mechanochemical Cell Biology, Division of Biomedical Sciences, Warwick Medical School, where she investigates the mechanisms that regulate how embryonic cells form complex whole organisms. Using zebrafish as a model to understand organismal development, she has contributed substantially to our understanding of one of the most important signalling pathways in animal development, the Nodal pathway. She characterised the role of Nodal in zebrafish development where mutations affecting Nodal and the Nodal pathway causes cyclopia, and mimics a human syndrome called holoprosencephaly. Nodal signalling has now been found to be involved in a wide variety of processes including stem cell renewal and differentiation, positioning of internal organs including the heart and gut,  maintenance of adult tissues and malignancies. Dr. Sampath has continued her work into understanding how Nodal fine-tunes different aspects of vertebrate development, with her research featured in highly respected international journals. She has recently identified a novel post-transcriptional mechanism regulating Nodal signalling in early embryos, that may have broad consequences in regulating Nodal in a variety of contexts.

Discussion continues over drinks from 5:30 pm in The Weston Exchange Hub.

Part of the Living Systems Institute (LSI) seminar series. All welcome.

Location:

LSI Seminar Room A