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Understanding self-organised tissue patterning across scales

Lead Research Organisation: University of Sheffield
Department Name: Mathematics and Statistics

Abstract

As our body grows, how does each organ control its shape and form? We know that when this doesn't happen correctly, we can get developmental diseases or cancer. If we can understand the ways of controlling shape and form, then perhaps we will be able to intervene to correct these diseases. We know that each organ or tissue is made of many cells and each cell is made of very many molecules such as proteins. But how do many small molecules interact together so that each cell has the correct form, and how do many cells interact together to form an organ with the correct form, many millions of times larger than each molecule?

One important way that an organ can control its form is by correctly orienting its cells relative to each other. This is true not just in humans, but in all animals, including the humble fruit fly. Here, we plan to study the fruit fly wing, where we can quickly and easily do experiments to manipulate the production of particular proteins and explore how this affects the orientation of individual cells and, in turn, the shape and function of the whole tissue (in this case, a wing).

We will also use mathematics and physics to put our experimental evidence together and help us to understand these mechanisms, by simulating them in the computer and making predictions about how the proteins and cells of the wing should behave if we manipulate it in some way. We will then test these predictions by doing further experiments, which will allow us to decide if the original assumptions were correct and ultimately understand the principles behind how the coordination of cell orientation contributes to the form and function of animal organs.

Publications

10 25 50
 
Description Mechanisms of symmetry breaking at molecular and cellular scales in planar polarity
Amount £3,700,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2024 
End 10/2031
 
Title Chaste v2024.1 
Description Chaste - Cancer, Heart and Soft Tissue Environment is a C++ library for computational biology. It was first released open source in 2009. Latest code 2024 and available on www.github.com/Chaste/Chaste 
Type Of Technology Software 
Year Produced 2024 
Open Source License? Yes  
Impact Many international groups have made use of our software for a wide variety of applications, details on the website and twitter feed: https://twitter.com/Chaste_Project 
URL http://www.cs.ox.ac.uk/chaste
 
Description Science Festival (Sheffield) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact BioFest was a unique festival that brought exciting, cutting-edge bioscience research from the University of Sheffield to new audiences through a programme of free events, talks, exhibitions, films and podcasts. The festival explored how researchers are tackling the 5 biggest challenges facing humanity - climate change, food security, healthy ageing, antimicrobial resistance and biodiversity. A postdoctoral researcher funded by the award, Hongyu Shao, contributed to an exhibit aimed at educating attendees (particularly children aged 5-11) about planar polarity.
Year(s) Of Engagement Activity 2023
URL https://player.sheffield.ac.uk/series/biofest