Talented and motivated students passionate about doing research are invited to apply for this PhD position. The successful applicant will join the Crick PhD Programme in September 2022 and will register for their PhD at one of the Crick partner universities (Imperial College London, King’s College London or UCL).
This 4-year PhD studentship is offered in Dr Rashmi Priya’s Group based at the Francis Crick Institute (the Crick).
The overarching goal our lab is to address how simpler structures like a sheet of cells build intricate architecture of organs using a well-suited model system – the developing zebrafish heart. Heart is the first organ to form and function during embryonic development [1]. To supplement the increasing physiological demands of the growing embryos, the cardiac tissue develops numerous specialized structures for maximum efficiency. One such critical step in vertebrate cardiac development is trabeculation, which is crucial for heart function [1]. During trabeculation, the myocardial wall transforms from a single-layered epithelium into a complex 3D architecture consisting of two distinct cell types: outer compact layer and inner trabecular layer cardiomyocytes (CMs) [2-4].
We have recently shown that differences in the mechanical properties of CMs is sufficient to trigger this crucial morphogenetic event [3]. CMs with higher cytoskeletal tension delaminate from the outer layer to seed the inner trabecular layer and this spatial segregation is sufficient to induce differential cell fate program [3]. Eventually, these single trabecular CMs undergo morphological transformations to generate complex multicellular structures called trabecular ridges, which span the ventricular lumen (Fig. c-c’, asterisks). Trabeculation defects cause cardiomyopathies and embryonic lethality [1]. Yet, how the simple myocardial epithelium acquires intricate morphological complexity and diverse cell fates during trabeculation is not yet understood. Taking a systems biology approach, we aim to deconstruct this complexity by studying the developing zebrafish heart. Zebrafish embryos offer several distinct advantages to study heart development. The embryos are easily accessible, amenable to extensive genetic manipulations and are transparent, thus enabling us to visualize a beating heart at single cell resolution [5]. Most importantly, during the first week of development, zebrafish embryos can survive without a functional heart. This is a unique advantage, as it enables us to use experimental manoeuvres ablating heart functions, which is otherwise impossible to achieve in other model systems because of early lethality. Taking advantage of this powerful vertebrate model organism, some of the fundamental problems we seek to address are:
- How cell mechanics, shape, and polarity regulate its fate choices at the onset of trabeculation?
- How geometrical constraints like tissue curvature and fluid forces feedback to tissue morphogenesis during trabeculation?
- How extracellular matrix remodelling regulates emergence and maturation of trabeculae?
- Unravelling the underlying cell biology and physical forces that contribute to trabeculae maturation.
The suitable candidate will address one of these fundamental questions by using cross-disciplinary approaches from quantitative cell biology, state-of-art zebrafish genetics and theoretical physics; for e.g., 4-D live-imaging, quantitative image analysis, optogenetics, biophysical manipulations, live biosensors, knock-in technology and controlled genetic perturbations. The specific details and aims of the project will be developed in consultation with the supervisor and will be driven by the candidate’s interest and training.
Candidate background
I am particularly interested in receiving applications from candidates with a background in cell/developmental biology and an interest in using interdisciplinary approaches in their research. Laboratory experience in zebrafish embryological techniques, confocal imaging, image analysis and molecular biology is desired but not essential.
Applicants should hold or expect to gain a first/upper second-class honours degree or equivalent in a relevant subject and have appropriate research experience as part of, or outside of, a university degree course and/or a Masters degree in a relevant subject.
APPLICATIONS MUST BE MADE ONLINE VIA OUR WEBSITE (ACCESSIBLE VIA THE ‘INSTITUTION WEBSITE’ LINK ABOVE) BY 12:00 (NOON) 11 November 2021. APPLICATIONS WILL NOT BE ACCEPTED IN ANY OTHER FORMAT.
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