BBSRC Thematic Group: Health
Physical interactions are crucial during morphogenesis. In order to shape tissues and organs, cells need to exert forces on their neighbours and respond to them. Individual cells can generate forces by using their actin cytoskeleton. Ongoing research seeks to understand in which ways mechanical interactions can contribute to morphogenesis and how they can be regulated.
Drosophila is an ideal model organism to study cytoskeletal activity and forces during morphogenetic events. In the Drosophila abdomen, larval epithelial cells (LECs) migrate and contract rhythmically to reduce cell size before undergoing programmed cell death (Pulido Companys et al., 2019). This rhythmic activity is driven by actomyosin contractility (Mason and Martin, 2011). Little is about known how such cytoskeletal dynamics are controlled in vivo. However, understanding this will be relevant to applications in wound healing, development, and metastases formation in tumours.
The aim of this studentship is to study the regulation of the contractile actomyosin network in single LECs in vivo, while they concurrently migrate and change cell shape. You will combine state-of-the-art in vivo 4D microscopy, quantitative image analysis tools, Drosophila genetics, and mathematical modelling to understand the interactions governing pulsed cytoskeletal dynamics.
4D microscopy will allow you to record pulsing cells during morphogenesis in vivo in great detail. Image analysis of the 4D movies will then enable you to study the behavior of the cytoskeletal network quantitatively using and developing state-of-the-art tools, including Particle Image Velocimetry and machine learning for automatic image segmentation. You will investigate how cytoskeletal dynamics emerge within constricting cells and how they are influenced by neighbouring cells pulling and pushing.
Developing a mathematical model will provide mechanistic insights into cytoskeletal regulation and the influence of cell-cell interactions. By quantitatively comparing the mathematical model to your generated data sets you will identify key regulatory spatial and molecular interactions governing cellular contractions. You will use the model to identify informative experiments that will help you gain deeper understanding of cytoskeletal dynamics.
This project is particularly well suited for students who are enthusiastic about developmental biology, and who are interested in interdisciplinary approaches that combine experiments and mathematical modelling.
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, image segmentation, 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.
Keywords: Drosophila, cytoskeleton, morphogenesis, developmental mechanics, mathematical modelling