Reverse Engineering Morphogenesis
Lead Research Organisation:
University of Warwick
Department Name: Warwick Medical School
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Publications
Lou Y
(2023)
Curvature-Induced Cell Rearrangements in Biological Tissues.
in Physical review letters
Theis S
(2024)
CellMet: Extracting 3D shape metrics from cells and tissues
| Description | Each of our organs has a specific shape necessary for its effective function - from multibranched lungs through to our delicate nervous system. Our organs develop during embryo formation, yet we know remarkably little about the processes driving formation of organs with specific shapes and sizes. This is an important challenge, as many diseases can be traced to a developmental origin. Recent years has seen the emergence of "organoids" - cell culture experiments that can mimic the processes happening inside the embryo. These have been studied largely from a genetics perspective to assess whether they faithfully replicate the cell types seen in embryos. Yet, formation of organs is also a physical process, with cells and tissues reshaping to make the specific organ morphology. In this work, we are dissecting the interplay between chemical signals and mechanics in building organs. We focus on a model for the developing lower spine. Our work is revealing the importance of boundary constraints in determining cell fates and how a group of cells can go from a flat tissue to a complex 3D shape. |
| Exploitation Route | Organ formation requires a close interplay between mechanics and genetics. Our work is helping bridge this gap and will be essential in building better models of how human organs form in embryos. |
| Sectors | Pharmaceuticals and Medical Biotechnology |
| Description | Joint meeting between Warwick and Cambridge Universities on Quantitative Methods in Developmental Biology |
| Geographic Reach | Local/Municipal/Regional |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | We had a focus on quantitative methods, such as machine learning approaches to image analysis. This 2-day meeting supported students and post-docs from biology to develop their skills in computer analysis and imaging. |
| URL | https://warwick.ac.uk/fac/sci/med/news/eventscal/warwick-cambridge_quantitative_cell/ |
| Description | Masters-level teaching on physics for biologists |
| Geographic Reach | Europe |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | Biology is becoming increasingly interdisciplinary. Yet, training of biologists is still focused on traditional approaches and does not integrate new methods from physics, engineering, computer science and mathematics. The Strasbourg Masters in Physics of Life is a novel approach that attempts to bridge this gap. As part of this, external speakers are invited to discuss their research and how they do interdisciplinary research. |
| URL | https://www.cellphysics-master.com/ |
| Description | Physics of Life roadmap |
| Geographic Reach | National |
| Policy Influence Type | Contribution to a national consultation/review |
| Description | MRC DTP Warwick |
| Amount | £100,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2022 |
| End | 09/2025 |
| Description | MRC DTP Warwick |
| Amount | £100,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2023 |
| End | 09/2026 |
| Description | MathSys DTP Warwick |
| Amount | £100,000 (GBP) |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2022 |
| End | 09/2025 |
| Title | CellMet: Extracting 3D shape metrics from cells and tissues |
| Description | During development and tissue repair, cells reshape and reconfigure to ensure organs take specific shapes. This process is inherently three-dimensional (3D). Yet, in part due to limitations in imaging and data analysis, cell shape analysis within tissues have been studied as a two-dimensional (2D) approximation, e.g., the Drosophila wing disc. With recent advances in imaging and machine learning, there has been significant progress in our understanding of 3D cell and tissue shape in vivo. However, even after gaining 3D segmentation of cells, it remains challenging to extract cell shape metrics beyond volume and surface area for cells within densely packed tissues. In order to extract 3D shape metrics, we have developed CellMet. This user-friendly tool enables extraction of quantitative shape information from 3D cell and tissue segmentation. It is developed for extracting cell scale information from densely packed tissues, such as cell face properties, cell twist, and cell rearrangements. Our method will improve the analysis of 3D cell shape and the understanding of cell organisation within tissues. Our tool is open source, available at https://github.com/TimSaundersLab/CellMet. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2024 |
| Provided To Others? | Yes |
| Impact | We have already had numerous labs download the software and use on their data. It has received positive reviews at PLoS Computational Biology and we hope for full acceptance by June 2025. |
| URL | https://github.com/TimSaundersLab/CellMet |
| Title | Organoid shape control |
| Description | Using micropatterned substrates, we are able to control cell fate and morphogenesis of human-derived organoids, which mimic human neural tube formation. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2024 |
| Provided To Others? | No |
| Impact | This tool provides unprecedented flexibility in exploring how our organs form. |
| Title | 3D Organoid model |
| Description | Using vertex models, we are building novel simulations to understand how complex shape emerges in development. |
| Type Of Material | Computer model/algorithm |
| Year Produced | 2023 |
| Provided To Others? | No |
| Impact | This will soon be written up and we will make all code available. |
| Description | Neuruloid morphogenesis |
| Organisation | Francis Crick Institute |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | This grant is a three way collaboration between James Briscoe (Crick), Guillaume Charras (UCL) and myself (Warwick). My team are developing theoretical models of neuruloid tissue morphogenesis. We are using both vertex-based and reaction-diffusion based approaches. We have already generated testable predictions that we are now exploring experimentally. |
| Collaborator Contribution | The Briscoe lab brings expertise in the initiation and growth of neuruloid cultures. They also have a deep understanding of the underlying biological networks that define cell fate within the neuruloids. The Charras lab has extensive experience in characterising the mechanical properties of biological tissues. They provide essential parameter estimates required for our modelling. |
| Impact | Work is still ongoing - the grant is <1 year. So, the collaborative elements of the research have yet to be published. |
| Start Year | 2022 |
| Description | Neuruloid morphogenesis |
| Organisation | University College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | This grant is a three way collaboration between James Briscoe (Crick), Guillaume Charras (UCL) and myself (Warwick). My team are developing theoretical models of neuruloid tissue morphogenesis. We are using both vertex-based and reaction-diffusion based approaches. We have already generated testable predictions that we are now exploring experimentally. |
| Collaborator Contribution | The Briscoe lab brings expertise in the initiation and growth of neuruloid cultures. They also have a deep understanding of the underlying biological networks that define cell fate within the neuruloids. The Charras lab has extensive experience in characterising the mechanical properties of biological tissues. They provide essential parameter estimates required for our modelling. |
| Impact | Work is still ongoing - the grant is <1 year. So, the collaborative elements of the research have yet to be published. |
| Start Year | 2022 |
| Title | CellMet: Extracting 3D shape metrics from cells and tissues |
| Description | During development and tissue repair, cells reshape and reconfigure to ensure organs take specific shapes. This process is inherently three-dimensional (3D). Yet, in part due to limitations in imaging and data analysis, cell shape analysis within tissues have been studied as a two-dimensional (2D) approximation, e.g., the Drosophila wing disc. With recent advances in imaging and machine learning, there has been significant progress in our understanding of 3D cell and tissue shape in vivo. However, even after gaining 3D segmentation of cells, it remains challenging to extract cell shape metrics beyond volume and surface area for cells within densely packed tissues. In order to extract 3D shape metrics, we have developed CellMet. This user-friendly tool enables extraction of quantitative shape information from 3D cell and tissue segmentation. It is developed for extracting cell scale information from densely packed tissues, such as cell face properties, cell twist, and cell rearrangements. Our method will improve the analysis of 3D cell shape and the understanding of cell organisation within tissues. Our tool is open source, available at https://github.com/TimSaundersLab/CellMet. |
| Type Of Technology | Software |
| Year Produced | 2024 |
| Impact | Multiple groups are already using the software to analyse their data. We hope that it will soon be accepted at PLoS Computational Biology after initially positive reviews. |
| URL | https://www.biorxiv.org/content/10.1101/2024.10.11.617843v1 |
| Description | British Biology Olympiad |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | My lab is now part of the team that helps run the British Biology Olympiad selection and training. This involves selecting the final team from 16 finalists. We then support in training the students for the International Biology Olympiad. |
| Year(s) Of Engagement Activity | 2025 |
| URL | https://ukbiologycompetitions.org/british-biology-olympiad/ |
| Description | Sutton Trust |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | 20 A-level pupils from disadvantaged areas/backgrounds visited Warwick University funded by the Sutton Trust over summer of 2022. As part of this, my team did a demo of our light microscopy and we talked about how we use organoids to understand how humans develop. This received very strong feedback and we are presenting to the Sutton Trust again this year. |
| Year(s) Of Engagement Activity | 2022 |