Team:KU Leuven/Journal/Modelling
From 2013.igem.org
Secret garden
Congratulations! You've found our secret garden! Follow the instructions below and win a great prize at the World jamboree!
- A video shows that two of our team members are having great fun at our favourite company. Do you know the name of the second member that appears in the video?
- For one of our models we had to do very extensive computations. To prevent our own computers from overheating and to keep the temperature in our iGEM room at a normal level, we used a supercomputer. Which centre maintains this supercomputer? (Dutch abbreviation)
- We organised a symposium with a debate, some seminars and 2 iGEM project presentations. An iGEM team came all the way from the Netherlands to present their project. What is the name of their city?
Now put all of these in this URL:https://2013.igem.org/Team:KU_Leuven/(firstname)(abbreviation)(city), (loose the brackets and put everything in lowercase) and follow the very last instruction to get your special jamboree prize!
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Week 1: The modelling team is on fire!
The modelling team is ready to rock Matlab after watching some tutorials and webinars about modelling and Symbiology.
We are excited to get our modelling team going and therefore we had an appointment with professor Bernaerts. It was very useful, as she gave some good ideas on how to get started. We will have to design a way of expressing the enzyme(s) in a cyclic manner and a possible way to achieve this would be by expressing it during a short pulse, stimulated by the presence of a signal from other cells.
And to tackle this problem we also started brainstorming about some possible networks with oscillating behavior. Here we have to keep in mind that the bacterial colonies have to get and stay synchronized and this might be achieved by a rapid (protein-protein interaction) feedback which is proportional to the phase difference. In an attempt to collaborate with the wetlab team we discussed our main focus for the upcoming weeks: figuring out an oscillating construct and simulating the behaviour of the methyl salicylate BioBrick.
And since organization comes after thought Bert and Sander started working on simulating the Mortier Oscillator (as Bert likes to call it) in SimBiology, while Tina and Tomas started modelling the network to produce methyl salicylate by looking at BSMT1(the enzyme that catalyzes the reaction from salicylate to methyl salicylate) and at pchA and pchB which catalyze the reactions from chorismate to isochorismate to salicylate.
Later this week Tina had a look on how to use the COBRA toolbox for our purpose and we would have to check the constraints on reaction rates and add our new reactions.
Bert contacted professor Suykens and professor Degrève to get an idea of how to analyse the MO. He gave the advice towards a bifurcation analysis, on which Bert will have a closer look.
Tomas on the other hand started on the development of another oscillator and contacted professor Roose of mathematical engineering, who suggested the use of MatCont.Furthermore we are also considering a strategy of a knock-out/knock-down of genes responsible for chorismate mutase and chorismate lyase to optimize methyl salicylate production.
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Week 2: From the Mortier Oscillator to COBRA and back
This week the AutoBioCAD software is keeping us busy!
Besides this we started investigating the literature of ecology and looking into a better model for our quorum sensing system using PDEs. We chose aphid and crop as our model species and now we’ll try to model aphid reproduction together with the influence of bèta-farnesene and methyl salicylate on life cycle and movement. We’ll have to make an estimation of the damage/loss of crops due to a certain population of aphids.
Meanwhile Bert added spatial heterogeneity to his Mortier Oscillator to see what happens on the population level.
(For some more mathematical information we would like to refer you to : Murray - Mathematical Biology)
We also had a meeting with Jonas Demeulemeester this week, who explained us the methods the modelling team of 2008 used. It was a lot of help to us and now we are off for a new start! Sander started to complete our model in SimBiology, integrating the DNA, RNA, protein and metabolite level. Tina will look further into the application of FBA and COBRA in our project. Tomas will continue modelling the diffusion of the pheromones and their effect on the insects and was finally able to solve the 2D PDE in Matlab, he refined the PDE and boundary conditions for the diffusion. A more realistic model for the wind speed was now used.
We also had a small meeting with our wetlabteam colleagues to look for a possible integration of our modelling approaches in the wetlab approach.
And in between all this we started an extensive literature study in the hope to find the right kinetic paramaters for our model in SimBiology.
We also discussed the possibility and usefulness of a q-PCR experiment and decided that Sander will perform the experiment next week at the CMPG (centre for microbiological and plant genetics)
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Week 3: Meeting professionals and digging into the literature
This week we continued the literature search for optimal transcription and degradation rates. and the exploration of the COBRA toolbox.
We also looked at the possible implementation of COBRA in the general approach of our project. Tina tried to implement our model in COBRA by adding the different parameters for the LB medium, found in the literature as a list of extracellular metabolites available in the LB medium for uptake but there are still some questions left unanswered regarding the COBRA toolbox, therefore we contacted Professor Bernaerts again,but unfortunately she is out of office until the 5th of august.
Therefore we had a look at what different approaches we could take while putting the COBRA part on a low profile for a while until her return.
We looked into motiontracking for which we contacted a person skilled in the art, Tim Tambuyzer. To gather some information on the nCounter Technology we contacted Nucleomics Core and scheduled a meeting with dr. Allemeersch, the ncounter technology was not useful for our project though since it would be rather an overkill, finally we also had a meeting with Prof. Aertsen of the centre for Food and Microbial Technology about implementation of networks in vivo. -
Week 4: Computational superspeed and oldschool Matlabcoding
Tomas is back on track to finetune his model for diffusion, while Bert is thinking about the correct way to verify the model. He is writing a matlab code in order to verify the oscillator.
Tina on the other hand is looking deeper into GapFilling of our model in the COBRA toolbox while Tomas got an account to the HPC cluster and 1000 credits. As it Seems waiting for a MATLAB job to be done is something from the past!
Later this week Bert and Tina had a meeting with Tim Tambuyzer, to talk about the options of videotracking and with prof. dr. ir. Dirk Roose to talk about possible analysis methods for the oscillator model. Meanwhile Sander was shedding blood, sweat and tears on the q-PCR!
Besides this we already started rocking some wiki texts.The pages are getting filled! -
Week 5: Awfully long wiki text alert!
Our days have started to look very similiar now, so besides the usual stuff we finally had a meeting with prof. Bernaerts again to tackle some COBRA problems and she helped us back on track!
Bert started writing a second text regarding the Oscillator analysis while Tina is becoming super best friends with COBRA and Sander is preparing for the presentation of tomorrow.
Later this week Sander had a meeting with prof. Engelborghs to get some clarification about enzyme kinetics for the parameter model and Tomas is back on track for his ecological model and installed COMSOL for this purpose. Bert is also still writing awfully long wiki texts by the way.
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Week 6: No obligatory days off for the modelling team!
On the 18th of august, the KU Leuven was closed because of a national holiday. But this couldn’t stop us from working! We got interviewed by the ethics team! We had some philosophical reflections on ourselves and our project with our Philosophy students Michiel and Sam.
When we got back to modelling, Tomas took a look at the supercomputer framework in order to parallelize the calculations needed to analyze the oscillator. Bert is looking in the literature for good parameter ranges. Sander continued on the parameters model.
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Week 7: Wikitexts,modelling,wikitexts...
COMSOL modelling seems to work out and realistic parameters have been found.
Tina started writing a wikitext regarding the COBRA analyses while Sander found out that doing a qPCR on plasmids is hard as it’s not easy to get rid of plasmid DNA contamination, so we’re working on a solution.
The wiki text about Ecology and the matlab code for the biggest part of the verification of the oscillator are near completion. -
Week 8: Tomas and Tina traded Bert and Sander for some insects (the difference is insignificant)
Tomas and Tina are spending a week at PCFruit to perform the insect experiments while Sander and Bert continue the good old fashioned modelling work! The finish line is in sight! The future will be dedicated to writing wiki texts.