Postdoctoral Fellow
Lifelancer
The overarching goal of our lab is to study how functional organs are built to sustain life during embryonic development. This is a long-standing problem in biology with significant implications for tissue engineering and birth defects. To solve this fundamental problem, we use a well-suited model system, the developing zebrafish heart, as it is amenable to state-of-art optical, biophysical, genetic manipulations. We take a systems biology approach by integrating tools from tissue mechanics, developmental genetics, transcriptomics, biophysics and predictive theoretical modelling.Using these approaches, we dissect the morphogenesis of a complex organ like heart at exceptional details, in the physiological context of a living embryo.A key step during vertebrate heart development is chamber maturation a poorly-understood morphogenetic process critical for heart function. During this process, the myocardial wall of ventricle and atrium transforms from a single-layered epithelium into a complex 3D topological meshwork architecture. In ventricle, this meshwork-like structures are called trabeculae, while in atrium they are referred to as pectinate fibers. Anomalous morphology and patterning of these structures lead to embryonic lethality and cardiomyopathies in human. Yet, cellular and physical mechanisms shaping myocardial meshwork remains ill-understood. Combining the excellent tractability of zebrafish with interdisciplinary approaches, some of the fundamental questions we seek to address are:1) How cell mechanics, shape, and polarity regulate its fate choices during heart development?2) How tissue geometry spatially constrains proliferation and delamination by dissecting the role of extracellular matrix (ECM) remodelling, fluid mechanics and mechanochemical pathways (feedback between Yap/Taz, ERK and Notch signalling).3) How 3D topological trabecular meshwork is shaped and constrained during development and how it supports heart function?4) Why and how atrium morphogenesis is differently regulated from ventricle by dissecting the underlying cell mechanics, differential ECM regulation, fluid dynamics and genetic pathways.The suitable candidate will address one of these questions by using advanced microscopic techniques, image analysis, genetic/optical manipulations, biophysical approaches and in collaboration with theoreticians. The specific details and aims of the project will be driven by the candidates interest and training. Candidates with a strong background in advanced imaging approaches, image analysis techniques, tissue morphogenesis/mechanics are encouraged to apply.Key responsibilities
Key experience and competenciesThe interested candidate should be keen in pursuing collaborative research, should be a good team player and should convey clearly in their application why they are interested in the labs research program.Essential
Desirable
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London
Thu, 11 Jul 2024 22:50:16 GMT
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