Background
During morphogenesis, cells undergo complex behaviours, including cell movement and apical constriction, to shape tissues and organs. Physical forces are crucial to drive such behaviour. It is becoming increasingly clear that to create forces, cells require rhythmical contractility of their cytoskeleton (Mason and Martin, 2011). For example, cell migration can be associated with oscillations of the leading edge, and pulsed contractions of actomyosin networks drive apical constriction and intercalation (e.g. during gastrulation, dorsal closure and germband extension in Drosophila and neurulation in vertebrates). Little is about known how such dynamic cytoskeletal activity is controlled in vivo. Understanding rhythmical cytoskeletal activity will not only provide key insights into morphogenesis, but also help decipher the mechanism underlying diseases caused by defective cell behaviour and tissue repair. For instance, during tumour progression, cancer cells change their behaviour, become motile and form metastases.
Project
Drosophila is an ideal model organism to study rhymical cytoskeletal activity and forces during morphogenesis. During the formation of the adult abdominal epidermis, the larval epithelial cells (LECs) undergo directed cell migration and apical constriction, during which they show pulsed contractions (Bischoff, 2012; Pulido Companys et al., 2020). This rhythmic activity is driven by actomyosin contractility. The aim of this studentship is to study the regulation of the contractile actomyosin network in single LECs in vivo. You will combine state-of-the-art in vivo 4D microscopy and Drosophila genetics to identify novel regulators of pulsed contractions. Interesting phenotypes will be studied using computational image analysis tools and state of the art statistical methods, which will be developed in collaboration with the Kursawe lab (School of Mathematics and Statistics, St Andrews). These methods will allow careful quantitative analysis of cytoskeletal dynamics. Studying the molecular mechanisms by which contractions are switched on and off, a major question you will tackle is how rhythmicality of pulsed contractions is generated. This interdisciplinary project is well suited for students with a background in the biological sciences, who aim to develop more computational skills.
Research environment
You will be able to work in two labs with complementing expertise. The Bischoff lab has extensive expertise in in vivo 4D microscopy of Drosophila morphogenesis (http://synergy.st-andrews.ac.uk/bischoff/), while the Kursawe lab is very experienced in quantitative image analysis and mathematical modelling of spatial interactions (https://risweb.st-andrews.ac.uk/portal/en/persons/jochen-kursawe(c18cd22b-def7-4bf0-9494-f780aa9a3663).html). The University of St Andrews, Scotland’s first university, offers a collaborative and supportive research environment, which provides top-level training and excellent imaging facilities. In addition, a wide range of taught courses is available, which will equip you with valuable transferable skills.
Eligibility requirements: Upper second-class degree in Biology or a related area.
Contact for informal enquiries: Dr Marcus Bischoff ([Email Address Removed])
How To Apply
Please make a formal application to the School of Biology through our Online Application Portal.
We require the following documents; CV, personal statement, 2 references, academic qualifications, English language qualification (if applicable).
Keywords: Cytoskeleton, pulsed constrictions, actomyosin contractility, tissue morphogenesis, Drosophila
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