About the Project
Physical interactions between cells 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 cytoskeletal dynamics contribute to morphogenesis and how they can be regulated. Understanding this will also provide insights into the mechanisms underlying wound healing and tumour formation.
Drosophila is an ideal model organism to study cytoskeletal activity and forces during morphogenesis. In the Drosophila abdomen, larval epithelial cells (LECs) migrate and contract rhythmically to reduce their apical area before undergoing programmed cell death (Pulido Companys et al., 2020). This cell shape change is driven by pulsed actomyosin contractions (Mason and Martin, 2011). Little is about known how such dynamic cytoskeletal behaviour is controlled in vivo.
The aim of this interdisciplinary studentship is to study the regulation of pulsed contractions in single LECs in vivo. You will combine state-of-the-art in vivo 4D microscopy, quantitative image analysis tools, Drosophila genetics and mathematical modelling to understand the molecular interactions governing pulsed cytoskeletal dynamics. 4D microscopy will allow you to image pulsing cells during morphogenesis in vivo in great detail. Image analysis of the 4D movies will then enable you to study the behaviour of the cytoskeletal network quantitatively using and developing state-of-the-art methods, including Optical Flow Analysis and machine learning for automatic image segmentation. You will investigate how cytoskeletal dynamics emerge within constricting cells and how they are influenced by cellular signalling.
Developing a two-dimensional mathematical model of actomyosin contractility, based on an existing one-dimensional model (Banerjee et al., 2017), will help providing mechanistic insights into pulsed contractions. You will use the model to identify informative experiments that will help you gain deeper understanding of cytoskeletal dynamics. This 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, computer science, or physics background, who aim to delve into biology.
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
In order to apply for this position, please follow the application instructions under http://www.eastscotbiodtp.ac.uk/how-apply-0 to obtain the EASTBIO Application form.
Then, submit the EASTBIO application form and your academic transcripts as part of a formal online application- https://www.st-andrews.ac.uk/study/apply/postgraduate/research/
In the online application form, you will be asked to provide contact details for two academic references. Please ask your referees to use the EASTBIO reference form provided under the link above when preparing their support letter, and to ensure references are provided by the deadline on 6 January 2021.
This opportunity is open to UK and International students and provides funding to cover stipend and UK level tuition. For international candidates, the University of St Andrews will cover the Home-International fee difference. Please refer to UKRI website and Annex B of the UKRI Training Grant Terms and Conditions for full eligibility criteria.
Mason and Martin (2011), Curr Opin Genet Dev 21, 671–679.
Pulido Companys, Norris, and Bischoff (2020), J Cell Sci 133, jcs235325.
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