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Investigating the molecular mechanisms underlying pulsed contractility during Drosophila morphogenesis


School of Biology

Sunday, December 13, 2020 Competition Funded PhD Project (Students Worldwide)

About the Project

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 cytoskeletal dynamics are 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 optical flow analysis and other computational image analysis tools, 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, or students from a mathematics or physics background, who aim to delve into biology.

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 image segmentation (https://risweb.st-andrews.ac.uk/portal/en/persons/jochen-kursawe(c18cd22b-def7-4bf0-9494-f780aa9a3663).html). This will allow you to become proficient in both experimental and computational approaches to studying a biological system. 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.

Keywords: Apical constriction, cytoskeleton, pulsed contractility, tissue morphogenesis, Drosophila

Applications can be made online via our online portal- https://www.st-andrews.ac.uk/study/apply/postgraduate/research/

Funding Notes

Eligibility requirements: Upper second-class degree in Biology or a related area.

Funded PhD Project (UK and international students (including EU)). The studentship covers the tuition fees and a living allowance for a duration of 3.5 years.

Enquiries from Chinese nationals are also welcomed as the University of St Andrews has additional funding opportunities for Chinese students.

References

Mason and Martin (2011). Curr Opin Genet Dev 21, 671–679.

Bischoff (2012). Dev Biol 363, 179-190.

Pulido Companys et al. (2020). J Cell Sci 133. jcs235325.

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