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Team:Dundee/Modeling/netlogo
From 2014.igem.org
NetLogo
Modelling Comes to Life
Introduction
NetLogo is “an agent-based programming language and integrated modelling environment” and we used it to develop simulations to see the effects of space within the cell for the PQS and BDSF systems. NetLogo is an easy-to-implement tool and is part of the class of individual-based models (IBMs). The video below is an example run of the one of the PQS simulations.
Objectives
We wished to use the NetLogo IBM for two main purposes: (i) an investigation of potential intracellular spatial effects in the signalling pathways and (ii) the development of an easily accessible graphical user interface for the modelling component of the project.
Intracellular Spatial Effects
We discuss the results pertaining to the PQS system. Similar results were obtained for the other systems. The NetLogo model represents a cross-section of our E. coli chassis.
The spatially extended stochastic simulations generated by NetLogo exhibited broadly similar general trends as predicted by the other mathematical tools that we used. For example in Fig 1, we can see that increasing the number of signalling molecules increases the number of fluorescent molecules produced. Although we could not achieve close quantitative agreement with our other predictions, NetLogo did allow us to better visualise the effects of changing the number of signalling molecules, receptors and promoters on the expression of mCherry.
Graphical User Interface - Modelling Comes to Life
Since our project focuses strongly on public engagement, we realised that we would need to have a clear, non-technical and, most importantly, interactive method of explaining the science of the project to potential users of The Lung Ranger/L.A.S.S.O. and wider public. The NetLogo simulations provided a really useful visual aid for explaining how the biological systems worked. For instance, when we presented our project at the UK Cystic Fibrosis Trust Conference our audience included clinicians, patients and parents. The feedback received afterwards highlighted that the science had been understood because of the NetLogo animation.
Conclusion
NetLogo provided a good qualitative comparison with the ODE and SSA models indicating that intracellular spatial effects were sufficiently captured on average by the more quantitative ODE/SSA approaches. Future work would include the development of our model into a 3D simulation so we could more fully study these intracellular spatial effects. The most striking and useful aspect of this software was its ability to take the science, modelling and project as a whole into the hands of users.
Give it a Go:
Download NetLogo
http://ccl.northwestern.edu/netlogo/
Download our model
http://modelingcommons.org/browse/one_model/4150#model_tabs_browse_info
Play!
Welcome to Dundee's 2014 Wiki (Site Information)
Cystic Fibrosis is a genetic disease that results in the accumulation of thick mucus in the epithelial linings of the entire body, particularly the respiratory tract. Over the course of a patient’s life, the mucus-lined lung epithelium becomes repeatedly infected with pathogenic bacteria that stimulate an immune response; leading to inflammation, tissue damage, and ultimately, respiratory failure.
The microflora of the Cystic Fibrosis lung changes over time. In childhood, the major coloniser is Staphylococcus aureus, but as the patient matures other bacterial pathogens infect. The later-dominating pathogens, Pseudomonas aeruginosa and Burkholderia cepacia, are very difficult to eradicate and are associated with chronic decline in lung function. Burkholderia is so infectious that patients have to be isolated from one another, and can be denied lung transplants due to the persistence of this bacterium.
It is important, therefore, for medics to monitor and identify the levels of bacteria within the respiratory tract of a Cystic Fibrosis patient. Currently, patients must provide sputum samples and identification of bacteria takes between 72 hours and 2 weeks, by which point the bacteria can be in an antibiotic resistant state.
The Dundee 2014 iGEM project is focused on designing and testing a device that will rapidly and non-invasively identify the bacteria colonising a Cystic Fibrosis patient. Three biosensors will be developed that recognise external signal molecules produced by key bacteria, all of which are known to be in sputum samples of Cystic Fibrosis patients. A quinolone signal (PQS) is produced by Pseudomonas aeruginosa, a Diffusible Signal Factor (DSF) is produced by Stenotrophomonas maltophilia, an organism that is also associated with Cystic Fibrosis lung infection in adults, and BDSF is a related, but chemically distinct molecule that is produced by Burkholderia cepacia.
By engineering signal recognition and signal transduction proteins from these biological systems the Dundee iGEM team want to produce a portable electronic device that will identify infection outside of the clinic, so that patients do not have to travel great distances, and can be used to help health professionals make informed and rapid decisions on antibiotic treatments.
Read this again by clicking on Site Information in the navigation bar!
Bulletin Board (Policy & Practice)
Come look at the poster explaining how we involved the local and national Cystic Fibrosis community in our project, how we listened to people on the front line of the disease and how they affected our project.
School (Project)
Come in and learn about all the parts that make The Lung Ranger. The lab work that we carried out over the summer is explained here in detail, along with the modelling and implementation.
Library (Log Book)
Read about the experience the team has had over the summer. A week by week description of our work, how we carried out that work and some photos of our time together.
Saloon (iGEM community)
Come on in, take a seat and learn how we have interacted with the larger iGEM community. Who the team are, who helped them and how we helped others.
College of Life Sciences
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