Multilevel Modelling of Morphogenesis

Lead Research Organisation: John Innes Centre
Department Name: Contracts Office

Abstract

The core research focuses on developmental processes through a unique style of multilevel-modelling. By integrating gene regulatory networks and biophysical properties of single cells, through cell deformation, motion and tissue level properties, we study emerging phenomena on the level of multiple cells, organs, as well as the development of whole organisms. To do so, we are coupling the Cellular Potts Model, a model formalism that is very powerful for describing the biophysics of cell dynamics, to gene regulations and metabolics. Mathematical and computational techniques are applied to study the behaviour that emerges from the model at different intermediate levels of organisation, as well as at the level of the whole organism. It provides a framework in which experimental findings related to metabolism and gene regulation can be linked to the observed development, from the cellular level to the level of the whole organism. The focus is towards developmental mechanisms in plants, but with a strong emphasis on the similarities and differences these exhibit to animal development, to overcome the strong segregation that prevails in scientific literature between plant and animal studies that obscures the identification of striking similarities and conserved core mechanisms. Integrated studies of developmental biology requires the cycling between modelling, imaging and experiments. We are developing methods to derive cell shape and time dynamics from (time series of) (3D) images, as well as ways to determine and correct for biases in imaging data, and to extend this by generating through the image analysis substrates for in silico studies. This strategy allows us to test proposed gene regulatory networks, transport mechanisms, etc, using computational techniques and realistic, experimentally measured cells shapes and tissue organisations. To finish the loop, the modelling insights are then used to further steer the experiments.

Publications

10 25 50
 
Description * A novel method for automated and quantitative assessment of complex cell shapes, including features such as protrusion number and amplitude, with demonstrated functionality for Arabidopsis, Drosophila and in silico cells, has been made publicly available (SanchezCorrales, Development (2018)).
• We combined theory and tracking of plant leaves, proposing a new paradigm for cell division behaviour in the epidermis: cell division control also takes neighbourhood relations into account. (Carter, Development (2017)).
Exploitation Route For example, software to analyse tissue topology of Arabidopsis leaves has been made publicly available (Carter, Development (2017)) and is currently already being used by other groups for additional analysis on Arabidopsis leaves as well as other tissues.
Sectors Agriculture, Food and Drink,Digital/Communication/Information Technologies (including Software),Education,Pharmaceuticals and Medical Biotechnology,Other

 
Description Our mathematical findings have been used to understand stem cell dynamics in general. Our imaging analysis methods are being used to understand spatio-temporal dynamics of plant tissue. Our multi-cellular models are being used to understand organogenesis and meristem growth in plants as well as self-organisation in animal immune systems.
First Year Of Impact 2013
Sector Agriculture, Food and Drink,Education,Pharmaceuticals and Medical Biotechnology,Other
 
Description EMBO Practical Courses and Workshops
Amount € 33,000 (EUR)
Organisation European Molecular Biology Organisation 
Sector Charity/Non Profit
Country Germany
Start 07/2017 
End 07/2017
 
Description HFSP Research Grant
Amount $242,594 (USD)
Organisation Human Frontier Science Program (HFSP) 
Sector Charity/Non Profit
Country France
Start 08/2015 
End 07/2018
 
Description Modelling multicellular dynamics within immunological context 
Organisation Centre for Genomic Regulation (CRG)
Country Spain 
Sector Academic/University 
PI Contribution Develop a multi-level modelling framework to study multicellular dynamics, here specifically within an immunological context.
Collaborator Contribution Apply the framework to tackle issues related to the build-up of immunological responses.
Impact Multi-disciplinary research, involving mathematical modelling and experimental biology.
Start Year 2014
 
Description Modelling root stem cell niche regulation 
Organisation University of Wageningen
Country Netherlands 
Sector Academic/University 
PI Contribution Developing multi-level models of root development and stem cell regulation.
Collaborator Contribution Experimental work on Arabidopsis to explore and verify theoretical concepts and insights from the modelling.
Impact -Paper in Cell and other papers.
Start Year 2010
 
Description Petiole form regulation: a modelling-experiment cycle 
Organisation Utrecht University
Country Netherlands 
Sector Academic/University 
PI Contribution We have developed both data analysis techniques and in silico models to understand how organ shape can be achieved through a delicate balance between cell expansion and cell division.
Collaborator Contribution Experiments were performed to test hypotheses generated through the modelling regarding the fast and slow timescales involved in petiole form regulation.
Impact We published 2 papers. Multi-disciplinary collaboration, involving experimental biology (by the team of Martijn van Zanten) and mathematical modelling (by my team)
Start Year 2010
 
Description somitogenesis in the chick embryo 
Organisation University of the Algarve
Country Portugal 
Sector Academic/University 
PI Contribution Developing multi-level models of somitogenesis. Developing new ways to analyse PCR data. Developing mathematical models for the interaction between hox expression and the clock underlying somitogenesis.
Collaborator Contribution Using the chick embryo as a model system, performing experiments to verify and challenge modelling concepts.
Impact -2 papers are currently in preparation. -Multi-disciplinary, involving mathematical biology, biophysics and experimental biology
Start Year 2010
 
Title Kilombo 
Description A Kilobot simulator to enable effective research in swarm robotics 
Type Of Technology Software 
Year Produced 2016 
Impact TheKilobotisawidelyusedplatformforinvestigationofswarmrobotics. Physical Kilobots are slow moving and require frequent recalibration and charg- ing, which significantly slows down the development cycle. Simulators can speed up the process of testing, exploring and hypothesis generation, but usually re- quire time consuming and error-prone translation of code between simulator and robot. Moreover, code of different nature often obfuscates direct comparison, as well as determination of the cause of deviation, between simulator and actual robot swarm behaviour. To tackle these issues we have developed a C-based simulator that allows those working with Kilobots to use the same programme code in both the simulator and the physical robots. Use of our simulator, coined Kilombo, sig- nificantly simplifies and speeds up development, given that a simulation of 1000 robots can be run at a speed 100 times faster than real time on a desktop com- puter, making high-throughput pre-screening possible of potential algorithms that ould lead to desired emergent behaviour. We argue that this strategy, here specif- ically developed for Kilobots, is of general importance for effective robot swarm research. The source code is freely available under the MIT license. 
URL https://github.com/JIC-CSB/kilombo
 
Description Connecting Nutrition and Health (Earlham institute) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact This workshop looks at the integration of omics data, with a particular focus in the fields of health and nutrition as well as environmental factors influencing health.
Year(s) Of Engagement Activity 2017
 
Description DTP Course on Computational and Systems Biology 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact I organised a 4-week hands-on course for around 25 DTP students to learn basics of systems biology in its broadest sense. It changed their way of looking at the role modelling, theory, mathematics and computational science plays in modern biological science.
Year(s) Of Engagement Activity 2017,2018
 
Description DTP Course on Systems Biology 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact I organised a 1-week advanced hands-on course for 16 DTP students to learn in-depth computational biology and bioinformatics. It changed their way of looking at the role modelling, theory, mathematics and computational science plays in modern biological science.
Year(s) Of Engagement Activity 2017
 
Description DTP Courses on Computational and Systems Biology 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact I organised both one 4-week and one 1-week hands-on course, each one for around 25-30 DTP students to learn basics of systems biology in its broadest sense, targeted to audiences with different levels of systems biology engagement. It changed their way of looking at the role modelling, theory, mathematics and computational science plays in modern biological science.
Year(s) Of Engagement Activity 2018
 
Description DTP Introduction to Computational Biology 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact I organised a 4-week hands-on course for 26 DTP students to learn basics of systems biology in its broadest sense. It changed their way of looking at the role modelling, theory, mathematics and computational science plays in modern biological science.
Year(s) Of Engagement Activity 2016
 
Description EMBO MLMM 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Organized and held 2-week practical workshop on Multilevel Modelling of Morphogenesis.
Now this activity is run every 2 years, and attracts academic and industry researchers internationally.
Year(s) Of Engagement Activity 2010,2011,2013,2015
URL https://www.jic.ac.uk/whats-on/events/2015/07/embo-practical-course-2015/
 
Description JIC Science for Innovation Showcase 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Showcasing leading-edge science that can inspire industry, as well as 1-2-1 discussions between scientists and industry
Year(s) Of Engagement Activity 2018