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Team:KULeuven/Project
From 2008.igem.org
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Project brainstorm
Favourite previous iGEM projects
Maarten Breckpot
Nathalie Busschaert
Jonas Demeulemeester
- [http://parts.mit.edu/igem07/index.php/Ljubljana Virotrap Ljubljana 2007]
- [http://parts.mit.edu/igem07/index.php/Princeton RNAi enhanced logic circuit Princeton 2007]
- Other nice parts/devices:
- Caltech: Riboswitch design for targeted cell death/molecular sensor
- Cambridge: Inducible bigger pore protein for E.coli
- Harvard: Quorum-sensing & targeting!
- Melbourne: Red/blue light responsive system through chimeric photoreceptors-kinases
- Peking U: λ-based bistable switch = very powerful
- UCSF: compartmentalization! Rewired MAPK cascade signaling through scaffolds ≅ circuit board
Andim Doldurucu
Jan Mertens
- [http://parts.mit.edu/igem07/index.php/Ljubljana Virotrap Ljubljana 2007]
- [http://parts.mit.edu/igem07/index.php/Berkeley_UC Bactoblood]
Benjamien Moeyaert
- [http://openwetware.org/wiki/IGEM:Harvard/2006/DNA_nanostructures Harvard 20006: nanostructured DNA containers]
- [http://parts.mit.edu/igem07/index.php/Berkeley_UC Bactoblood]
Stefanie Roberfroid
- [http://parts.mit.edu/igem07/index.php/Cambridge Bacteria Online]
- [http://parts.mit.edu/igem07/index.php/Berkeley_UC Bactoblood]
- [http://parts.mit.edu/igem07/index.php/Princeton RNAi enhanced logic circuit]
- some other nice ideas
- [http://parts.mit.edu/igem07/index.php/Edinburgh Self-flavouring yoghurt]
- Detection of metals: [http://parts.mit.edu/igem07/index.php/Brown Lead], [http://parts.mit.edu/igem07/index.php/Saint_Petersburg Copper]
Hanne Tytgat
- [http://parts.mit.edu/igem07/index.php/Berkeley_UC Bactoblood]
- [http://parts.mit.edu/igem07/index.php/MIT Sensing & removing Hg ions - MIT 2007]
- [http://parts.mit.edu/igem07/index.php/Imperial/Infector_Detector/Introduction Infector detector]
Elke Van Assche
- [http://parts.mit.edu/wiki/index.php/MIT_2006 Eau d'E.coli MIT 2006]
- [http://parts.mit.edu/igem07/index.php/Berkeley_UC Bactoblood Berkeley UC 2007]
- [http://parts.mit.edu/igem07/index.php/Princeton RNAi enhanced logic circuit Princeton 2007]
Nick Van Damme
- [http://parts.mit.edu/igem07/index.php/Davidson_Missouri_W Bacterial Computer]
--> idea: solve a nice mathematical problem
- several electronical/biological components to build an entire complex combinational logic system
- [http://parts.mit.edu/igem07/index.php/USTC Extensible Logic Circuit in Bacteria]: both components and linking
- [http://parts.mit.edu/igem07/index.php/Valencia Comparator]
- [http://parts.mit.edu/igem07/index.php/Bologna Schmitt trigger]
--> idea: build an integrator to solve your own ODE's, also build a differentiator to make a PID-controller
Antoine Vandermeersch
- [http://parts2.mit.edu/wiki/index.php/University_of_Texas_2006 Texas 2006: Edge Detector]
- [http://parts.mit.edu/igem07/index.php/Rice/Project_B:_Quorumtaxis Rice 2007: Quorumtaxis]
- [http://parts.mit.edu/igem07/index.php/Berkeley_LBL Berkeley LBL 2007: Solar Bacter]
Dries Vercruysse
Sigrid De Keersmaecker
- [http://parts.mit.edu/igem07/index.php/MIT Sensing & removing Hg ions - MIT 2007]
- [http://parts.mit.edu/igem07/index.php/Edinburgh Self-flavouring yoghurt - Edinburgh 2007]
- [http://parts.mit.edu/igem07/index.php/Missouri_Miners Biological Timer - Missouri Miners 2007]
- [http://parts.mit.edu/igem07/index.php/Ljubljana Virotrap - Ljubljana 2007]
- [http://parts.mit.edu/igem07/index.php/Taipei/Taipei GlucOperon - Taipei 2007]
- [http://parts.mit.edu/igem07/index.php/Berkeley_LBL Solar Bacter - Berkeley_LBL 2007]
- [http://parts.mit.edu/igem07/index.php/Berkeley_UC Bactoblood - Berkeley_UC 2007]
iGEM judging tracks
- Foundational Research - basic science and engineering research
- Information Processing - genetically encoded control, logic, and memory
- Energy - biological fuels, feedstocks, and other energy projects
- Environment- sensing bioremediation of environmental state
- Health & Medicine - applied projects with the goal of directly improving the human condition
Other
[http://openwetware.org/wiki/IGEM:Idea_exchange Idea exchange - iGEM ideas posted by other teams]
Our project
Our abstract
A first idea: cancer treatment with genetically modified blood cells
As cancer cells need a lot of energy to replicate themselves, they should be well provided with blood. Therefore, blood cells could be the right choice for in situ treatment of cancer. First, we should immobilize these blood cells on the cancer cells. Subsequently, these blood cells should secrete specific agents that reduce the activity of the cancer cells. (These 2 steps may come in handy if we want to split up in 2 subgroups)
Notes
- Sounds like a great idea! [http://en.wikipedia.org/wiki/Avastin Anti-angiogenic therapy] is one of the big hopes for anti-tumor treatments. But let's keep in mind that angiogenesis (the formation of blood vessels) is only a late hallmark of tumors [http://www.google.be/url?sa=t&ct=res&cd=1&url=http%3A%2F%2Fwww.weizmann.ac.il%2Fhome%2Ffedomany%2FBioinfo05%2Flecture6_Hanahan.pdf&ei=-7E2SLbLGJCE1wblseHQDQ&usg=AFQjCNHirXaVMmdQNGl-72bk5jRva4106Q&sig2=L18rRG56VaP9wIB_mAENpA (more about these hallmarks of cancer -PDF)]. It is however a significant barrier to break through if the tumor has to grow past a certain (very limited) size. So this would be more like a therapy for later-stage malignancies, which would also be great because it's often the metastasis (the spreading of) of the tumor that is causing the more visible effects of the cancer. (pain, deterioration, ... and eventually, if untreated death). - Jonas 12:09, 23 May 2008 (UTC)
- Anyhow, if we proceed with this idea, it will be a challenge to get everything ready and produced in the erythrocyte (red blood cell) before it loses it's nucleus and thus also the ability to initiate de novo transcription. And to keep all this machinery silent in non-docked erythrocytes. I'm liking this challenge though. Besides this has an upside as well as I feel that consequences would be less severe in this non-cell if things go awry in the system. :) - Jonas 17:30, 23 May 2008 (UTC)
- I just thought of something that might be quite critical. If I recall correctly, there are 3 main ways in which tumors acquire blood supply.
- The first one is through a recapitulation of embryonic development. This is the recruitment of vascular endothelial precursors or the activation of local endothelium via factors like VEGF (angiogenic sprouting or intussusceptive growth). In this case, the 'vessels' of the tumor blood supply are lined mostly with endothelial cells which are actually NOT malignant, but are kind of working together with the tumor cells.
- A successful cancer metastasis (a secondary tumor, derived from the original) will co-opt blood vessels and these will thus also be lined mostly with endothelium cells.
- The third way to achieve blood supply is through vasculogenic mimicry, where the tumor cells actually DO line the bloodstream and mimic the normal vascular endothelium. Here tumor biomarkers should be directly displayed to the passing erythrocytes and would thus be potential targets for use in this approach.
- OK, now for my point. In all these cases the vessels are highly abnormal, both structurally and functionally. They've got many holes, inhomogeneous bloodflow, are leaky, ... so it's very likely there will be exposed markers we can focus on but this will probably not always be the case. So I'm really liking this idea! - Jonas 14:17, 23 May 2008 (UTC)
- There will be a lot of challenges. Some things that popped in my head: 1)What is the progenitorcell we're going to work with. When you use stemcells, you have to differentiate them in vitro into red blood cells which is pretty delicate matter. 2)finding the right markers for the recognition that are not expressed on normal cells. 3) developing an assay that proves that it works. Whith tis idea there are a lot of factors that have to be taken in account and the question is if we will get a positive result in 3 months time. There's a lot of ongoing research and a lot of things ar not yet known. But I also like the idea, next year I'm going to do my thesis about lymphangiogenesis so I'm very interested in the subject :)- Jan
A second idea: bacteria clean virusses in animals
This is an improvement of the idea of Ljubljana: we cannot reprogram the immune system, but we can reprogram bacteria. So, what we could do is make bacteria produce viral receptors (challenge 1) which are modified so that when a virus attaches to them, a restriction enzyme is transcribed (challenge 2). This RE degrades the viral DNA and the bacterial DNA, thus killing the bacterium. This way, the bacteria clean all virusses from the body. When this is established, we can induce a suicide signal for the bacteria (challenge 3). Big problems:
- Is it possible to make a eukaryotic virus attack a prokaryote (also a fundamental question)?
- Immunogenicity bacterium (cf. Bactoblood)! Bmoeyaert
- I'm probably risking to get banned for nagging because of this. :P I think the tricky part would be the preferential docking of the viruses on the bacteria if you've got about 10^14 of your own cells in your body. Even if only a small subset of these would be targets for the virus, I believe the ratio of bacteria to host cells would be quite low unless you allow a very large 'bacterial infection'. This problem might be overcome if the viral receptor density is way higher on the bacteria. - Jonas 17:52, 23 May 2008 (UTC)
- Cool stuff though, the opposite system exists. A bacterial infection could be treated by administering the specific bacteriophages, here the system can also co-evolve. Problem is that you have to know the bacterial strain of the infection in order to administer the correct phage, and this can take a while. - Jonas 17:52, 23 May 2008 (UTC)
- It's an appealing concept. An eukarotic virus only has to cross the celmembrane to get its content into the human cell. When we would use E.coli, the virus would have to get first through the outermembrane, then through the peptidoglycane and then through the innermembrane. So how does it get it in the cytoplasm? But maybe this is not necessary and is it sufficient to let the virus cross the outermembrane and come in the periplasm. If this induces the cell to do apoptosis en kill itself, including the virus, we've got a nice system. But like Jonas said, there will always be virusparticles that infect human cells, wich are in the majority. But still, it would be quite an accomplishment to get an eukariotic virus to infect a bacterium.-Jan
A third idea: Bacteria that control the amount of drugs
It's known that the effect of drugs on a human being is very dependent on the metabolism of that person. There are extensive metabolizers, people who have a normal response to a certain drug. Intermediate metabolizers show a low response and in poor metabolizers there's very little effect. Poor metabolizers need a higher amount of drugs to respond, where ultra fast metabolizers need a lower dose. These differences in the drugmetabolism in different people is a big concern, because a wrong dose can have severe consequences. There's a need for patient-focussed therapy. If we want to know which type of metabolizer a person is, we have to know his genotype. This is a very expensive and time-consuming procedure. Wouldn't it be nice to develop a two bacteria-system that can replace genotyping? I' m thinking of two bacteria that live together in the intestine. The first bacteria has a sensor function. It has to monitor if the amount of the drug that is present in the intestine, is efficient. This bacteria has to signal his observations to the second bacteria. This second bacteria is the drug-producer. Like some probiotics, that are already on the market, it produces the drug at the location where it's needed. The amount of drug it produces would be controlled by the other bacteria. In case the amount of treatment is enough, the first sensor-bacteria represses the second one. If the drug level drops again, the sensor-bacteria should re-activate the drug-producing one. In that way there's a feedback loop between the two bacterias and one can control the amount of treatment that's needed. --Hanne 19:27, 23 May 2008 (UTC)
- I don't think you necessarily need a 2 bacterial strain system and can also do it with one bacterial strain that has sensor- and drugproducer function. When it monitors the amount of drugs it can autoinduce itself to produce the drug and repress itself when it's enough. like the idea and think it's possible to do this in 3 months. It's also an idea in which I see our different skills can be integrated (the engineers can do modelling of pharmacokinetics for example), In the first 2 ideas that's maybe more difficult -Jan
