Dr Emily Noël
British Heart Foundation Intermediate Basic Science Research Fellow
Room C21 Firth Court
Brief career history
PhD Studentship Project
Investigating the links between embryonic laterality and asymmetric morphogenesis of the heart
Funding status: Competition funded project European/UK students only
This project is eligible for a department scholarship. These scholarships are awarded on a competitive basis – find out more on our funding webpage.
Congenital heart diseases occur in around 1% of live births, and are structural defects that arise from improper morphogenesis of the heart during embryonic development. Heart morphogenesis is a highly complex process, drawing on interplay of embryonic laterality cues, tissue rearrangements and cellular migration, and growth and differentiation.
The heart is a highly asymmetric organ. During early stages of development it forms an asymmetrically positioned linear tube that undergoes robust rightward looping to give rise to the looped heart. This stereotypic asymmetric morphogenesis is partly under the control of left-side derived asymmetric gene expression earlier during embryonic development. Importantly, in the absence of laterality signals, the heart can still undergo asymmetric looping morphogenesis, and questions still remain surrounding how this process may be driven, and how heart-extrinsic laterality signals and intrinsic morphogenetic processes are linked. Using transcriptomic analysis we have identified a small number of genes that are upregulated on the left side of the embryo during heart looping, and have been implicated in regulation of the extracellular matrix (ECM).
Furthermore, state of the art light sheet microscopy suggests differential ECM thickness between the left and right sides of the heart during early heart looping. Previous studies have implicated ECM deposition and degradation in earlier stages of heart precursor migration, and later roles in valve formation, however the link between embryonic laterality and asymmetric ECM in the heart is poorly understood.
We are looking for an enthusiastic PhD candidate to explore the link between early left-sided gene expression in the embryo, left-sided ECM deposition in the heart, and heart looping morphogenesis. The main aims of the project will be to:
1. Determine whether left-derived expression of ECM regulators/ECM deposition is under the control of asymmetric laterality cues.
2. Assess the impact of loss of asymmetric ECM deposition upon heart morphogenesis through developing loss-of-function and gain-of-function models.
We use zebrafish as a model organism to study heart development. Zebrafish represent a excellent model with which to study this process due to ease of genetic manipulation, and transparency during embryogenesis allowing us to visualize heart morphogenesis in real time in living embryos. Therefore, the project will provide training in zebrafish transgenesis, genome editing and mutagenesis, as well as state-of-the-art 4D imaging. It will further provide the student with the opportunity to become an expert in standard molecular biology, confocal microscopy, and image analysis. This project should be of particular interest to highly motivated students who have a keen interest in dissecting the molecular links that span embryo-wide signaling, tissue morphogenesis, and cellular responses, and who have an overarching interest in translational research and the genetic basis of congenital diseases.
Keywords: Cell Biology / Development, Genetics
For informal enquiries about the project or application process, please feel free to contact me.
For further information about projects within the department and how to apply, see our PhD Opportunities page:
- Noël ES, Momenah TS, Al-Dagriri K, Al-Suwaid A, Al-Shahrani S, Jiang H, Willekers S, Oostveen YY, Chocron S, Postma AV, Bhuiyan ZA & Bakkers J (2016) A Zebrafish Loss-of-Function Model for Human CFAP53 Mutations Reveals Its Specific Role in Laterality Organ Function. Human Mutation, 37(2), 194-200.
- Wu C-C, Kruse F, Vasudevarao MD, Junker JP, Zebrowski DC, Fischer K, Noël ES, Grün D, Berezikov E, Engel FB, van Oudenaarden A, Weidinger G & Bakkers J (2016) Spatially Resolved Genome-wide Transcriptional Profiling Identifies BMP Signaling as Essential Regulator of Zebrafish Cardiomyocyte Regeneration. Developmental Cell, 36(1), 36-49.
- Tessadori F, Noël ES, Rens EG, Magliozzi R, Evers-van Gogh IJA, Guardavaccaro D, Merks RMH & Bakkers J (2015) Nodal Signaling Range Is Regulated by Proprotein Convertase-Mediated Maturation. Developmental Cell, 32(5), 631-639.
- Junker J, Noël E, Guryev V, Peterson K, Shah G, Huisken J, McMahon A, Berezikov E, Bakkers J & van Oudenaarden A (2014) Genome-wide RNA Tomography in the Zebrafish Embryo. Cell, 159(3), 662-675.
- Noël ES, Verhoeven M, Lagendijk AK, Tessadori F, Smith K, Choorapoikayil S, den Hertog J & Bakkers J (2013) A Nodal-independent and tissue-intrinsic mechanism controls heart-looping chirality. Nature Communications, 4(1).
- Smith KA, Noël E, Thurlings I, Rehmann H, Chocron S & Bakkers J (2011) Bmp and Nodal Independently Regulate lefty1 Expression to Maintain Unilateral Nodal Activity during Left-Right Axis Specification in Zebrafish. PLoS Genetics, 7(9). View this article in WRRO