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Studying Tissue-Wide Coordination of Pulsed Contractions During Drosophila morphogenesis

School of Biology

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Dr M Bischoff , Dr Jochen Kursawe No more applications being accepted Competition Funded PhD Project (Students Worldwide)
St Andrews United Kingdom Biophysics Cell Biology Genetics

About the Project

The University of St Andrews is pleased to offer a full scholarship funded by St Leonard’s Postgraduate College, to support an exceptional student undertaking doctoral research in the following project:

Project description:

To create tissues and organs during development, animal cells undergo a range of behaviours, such as cell migration and constriction. It is becoming increasingly clear that many of these behaviours require rhythmical contractility of the cell’s cytoskeleton. For example, pulsed contractions participate in vertebrate neural tube formation and Drosophila gastrulation, a major reorganisation of the embryo during early development. Hence, understanding pulsed contractions is necessary to understand the shaping of tissues and organs as well as the mechanisms underlying developmental disorders, such as spina bifida (a neural tube defect).

What creates the rhythmicality of pulsed contractions remains elusive. One important unsolved question is whether rhythmicality of contraction is generated solely cell autonomously or whether it is influenced by external signals. As pulsed contractions occur tissue-wide, it is conceivable that mechanical forces created by a contracting cell can influence the pulsatile behaviour of its neighbours. However, studying tissue-wide pulsed contractions is challenging, as these involve not only the pulsating cytoskeletal network, but also the cell cortex, which lies underneath the cell membrane and gives the cell its shape and rigidity. It is experimentally difficult to manipulate one without affecting the other. Moreover, studying mechanical forces in vivo is challenging due to the inaccessibility of cells for force measurements inside intact organisms.

The aim of this scholarship is to address these challenges by using an interdisciplinary approach that combines quantitative image analysis and mathematical modelling to investigate tissue-wide pulsed contractions and mechanical interactions between neighbouring cells in vivo. Specifically, we will study the larval epithelial cells (LECs) of Drosophila. The Bischoff lab have recently shown that the LECs undergo pulsed contractions during the formation of the adult abdominal epidermis. LECs constitute a powerful system to uncover the mechanisms underlying pulsed contractions, due to their accessibility to in vivo microscopy and genetic manipulation.

The successful student will use in vivo 4D microscopy to image LECs using cytoskeletal and cell outline markers. Tissue-wide pulsed contractions of constricting LECs in the obtained 4D movies will then be analysed using automatic image segmentation tools. The student will adapt these tools to their needs and develop new methods where necessary, building on the existing image analysis experience in the Bischoff and Kursawe labs that combines conventional and machine learning approaches to image processing.

Accompanying this careful, quantitative characterisation of tissue-wide pulsed contractions, the student will generate a multi-scale mathematical model of cell shape regulation and tissue-wide cell-cell interactions. Here, they will use finite element methods to solve coupled partial differential equations that describe the viscoelastic deformations of the cytoskeleton and the cell cortex, as well as the mechanics of multi-cell interactions. The student will use the model to test the contributions of the pulsating cytoskeletal network and the cell cortex to tissue-wide cell constrictions in silico. Comparisons between model and experimental data on dynamic cell shape changes will enable the student to distinguish competing hypotheses on cytoskeletal regulation. In silico perturbations will help identify key experiments that can challenge our understanding of LEC constriction. This combination of modelling and experiments will enable us to explore to what extent mechanical forces acting on the constricting LECs are impacting on their pulsed contractions.

The student will be supervised by Dr Marcus Bischoff (School of Biology) and Dr Jochen Kursawe (School of Mathematics and Statistics).

Doctoral Research at St Andrews:

As a doctoral student at the University of St Andrews you will be part of a growing, vibrant, and intellectually stimulating postgraduate community. St Andrews is one of the leading research-intensive universities in the world and offers a postgraduate experience of remarkable richness.

St Leonard’s Postgraduate College is at the heart of the postgraduate community of St Andrews. The College supports all postgraduates and aims to provide opportunities for postgraduates to come together, socially and intellectually, and make new connections.

St Leonard’s Postgraduate College works closely with the Postgraduate Society which is one of the most active societies within the Students’ Association. All doctoral students are automatically welcomed into the Postgraduate Society when they join the University.

In addition to the research training that doctoral students complete in their home School, doctoral students at St Andrews have access to GRADskills – a free, comprehensive training programme to support their academic, professional, and personal development.

Duration of award:

Up to 3.5 years. The successful candidate will be expected to have completed the doctorate degree by the end of the award term. The award term excludes the continuation period and any extension periods.

Application procedure:

Informal enquiries regarding this scholarship may be addressed to Dr Marcus Bischoff – email [Email Address Removed]

Details of the eligibility criteria, and the application procedure are available via the official advertisement from the University of St Andrews webpages:

Note, that the final application deadline is 14 February 2021.

Funding Notes

The award covers full tuition fees for the award term as well as an annual stipend payable at the standard UK Research Council rate (the 2021-22 annual rate is £15,560).
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