Studying tissue wide coordination of pulsed contractility during morphogenesis in Drosophila

Applications are accepted now for anyone applying for Chinese Scholarship Council (CSC) funding only.
Applications already received by the initial 1 December deadline are now under consideration.

During morphogenesis, cells undergo complex behaviours, including cell movement and apical constriction to shape tissues and organs. Within developing tissues, cells can act individually or in coordination with their neighbours. The mechanisms underlying the coordination of cell behaviour in complex tissue contexts remain elusive. To gain insights into the regulation of cell behaviour, one must understand how it is generated by cytoskeletal activity. For instance, during cell migration, the formation of a lamellipodium helps propel the cell forward, whereas apical constriction is driven by rhythmical (pulsed) contraction of the actin cytoskeleton. Unravelling the cytoskeletal mechanisms underlying the orchestration of cell behaviours in contexts where many cells interact is not only crucial to understand how shape and form arise during development, but also to understand human disease and tissue repair. For instance, during tumour progression, cancer cells change their behaviour, become motile and form metastases. Similarly, wound healing depends on changes in cell behaviour, as epithelial cells must become motile to close a wound co-ordinately.

This studentship will study the coordination of cell behaviour using the larval epithelial cells (LECs) of the Drosophila abdomen as a model. During the formation of the adult abdominal epidermis, the LECs undergo directed cell migration and apical constriction, during which they show pulsed contractions (Bischoff, 2012; Pulido Companys et al., 2019). Little is known about how such dynamic cytoskeletal activity is regulated across the tissue to ensure correct formation of the abdomen.

The aim of this studentship is to investigate how LEC behaviour and underlying pulsed contractions are coordinated at the tissue level. The prospective PhD student will use in vivo 4D microscopy to image morphogenesis and apply automatic image segmentation and cell tracking tools. These methods will allow careful analysis of cytoskeletal dynamics and cell-cell interactions. Once normal development has been characterised, genetic manipulation of candidate signalling molecules will be used to explore which signalling pathways are involved in coordinating differences in cell behaviour throughout the tissue.

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.