IGEM:Caltech/2008/Ideas: Difference between revisions
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==Big Ideas== | ==Big Ideas== | ||
=== | |||
* | ===Bioremediation (or not)=== | ||
*So I guess I had failed to communicate my bigger picture about this idea. So removing materials is one thing that can happen, but the larger picture is getting a lot of independent bacteria (all in different states) together into one location such that information can be easily transmitted amongst the bacteria (through conjugation, etc). So say for instance that a particular bacteria has an important info that needs to be relayed to its neighbors. It can send a flag that will cause all the other bacteria is aggregate around it and pick up the signal. The neat thing about it would be that any bacteria can send a flag, so what we would get is a very dynamic network that has great potential. After the signal is sent, then all the bacteria can disperse and continue what they were doing before. So what we get is a bag of independent modules that can talk to each other (at least to its neighbors). I don't have an application for this, so maybe this idea is for the future. | |||
===Cholesterol Degradation=== | ===Cholesterol Degradation=== | ||
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**Similar idea, but use it for diabetes also and have E. coli feed off sugar. Maybe both? | **Similar idea, but use it for diabetes also and have E. coli feed off sugar. Maybe both? | ||
=== | ===Bacterial Mouthwash=== | ||
* | *Disrupt biofilms | ||
**I' | **Prophage targeting other bacteria | ||
*** | ***[http://www.jstor.org/sici?sici=0027-8424(19841001)81%3A19%3C6080%3AEOBHRS%3E2.0.CO%3B2-4&cookieSet=1 lamB] is sufficient for lambda infection. | ||
* | ***[http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=178622 Looking at other receptors] | ||
***[http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=375836 SPO2] is a lysogenic subtilis phage | |||
***How do we get the phage inside the cell? Take a resistant strain (coli w/o lamB for lambda, coli for a subtilis phage), add the necessary receptor on a plasmid. Infect, select for lysogens. Grow under nonselective conditions, then counterselect for loss of the plasmid. Voila. Tetracycline can be counterselected<cite>bochner</cite>. | |||
**Would it be possible to design our strain to prevent biofilm development? It might be a lot easier to target a few major strains in biofilm formation on our enamel w/o the biofilm to protect them. Would this be a possibility? [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2043269 Reduction of S. mutans adherence] | |||
**[[User:Josh K. Michener|Josh K. Michener]] 22:23, 11 May 2008 (EDT): See <cite>#kruger, kelly, younson, iwaki</cite> | |||
***'''[[User:Robert Ovadia|Robert]] 20:23, 12 May 2008 (EDT)''': After reading #5, if I understood correctly, the pac gene producing the PAc cell surface protein antigen binds to our tooth's surface. This in turn blocks <i>most</i> of the binding of S. mutans? So, if one would to have a "special" teeth cleaning removing bacteria from our mouth, and then have toothpaste (or mouthwash, etc.) of our non plaque forming strain (they used S. lactis), this would block the formation of S. mutans? If we were able to develop a steady growth rate of our strain (lets say L. lactis), we could hopefully keep a steady amount of S. lactis on our teeth blocking S. mutans from binding, and preventing plaque formation (I think!). | |||
***[[User:Josh K. Michener|Josh K. Michener]] 22:23, 12 May 2008 (EDT): S. mutants binds through PAc. So you can get competitive inhibition by expressing exogenous PAc. Either your engineered bacteria could attach using the same receptor, or you could bind something else and pump out PAc to compete off mutans. I think it's an open question whether you'd want to use S. lactis for this or try to get things working in E. coli. S. lactis would be easier initially, but any future work would be tough. I haven't been able to find anything on the functional expression of PAc in E. coli. Best I could find was some stuff that targeted it to the periplasm. | |||
***'''[[User:Robert Ovadia|Robert]] 02:05, 13 May 2008 (EDT)''': [http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=261150&blobtype=pdf McAb]. Disregard my previous question about this article. I didn't catch a key word in the article, but I understand it now. | |||
*H2O2 | |||
**Turn on xanthine oxidase, turn off catalase | |||
*Minty smell | |||
*Taste good? | |||
**[http://parts.mit.edu/igem07/index.php/Edinburgh/Yoghurt] | |||
**[http://en.wikipedia.org/wiki/Octyl_acetate Orange] | |||
**[http://en.wikipedia.org/wiki/Vanillin Vanilla] | |||
**Damascenone (fruity) | |||
**Ethyl-2-methyl butyrate (apple) | |||
*More important than avoiding having to floss: prevent dental problems in poor/underserved communities where lack of dental care can cause serious [http://www.redding.com/news/2007/apr/02/boys-death-from-tooth-infection-is-an-eye-opener problems]. | |||
===Gut microbiota=== | |||
*Food poisoning | |||
**[http://www.cbc.ca/health/story/2007/11/13/fecal-transplant.html Curing superbug infections] | |||
**[[User:Doug Tischer|Doug Tischer]] 20:51, 10 May 2008 (EDT) We could make a gut microbacteria that acts as a guard against the overgrowth of drug resistant bacteria. We could engineer E. coli that turns "hostile" if it detects the presence of say, a tetracycline resistant strain. Bacteria normally love to try to spread their antibiotic resistances, even between species, so I think it would be relatively easy to detect if there is a new bacteria that becomes tetracycline resistant. We could use a riboswitch to detect the presence of a resistance gene within the cell. Then we could engineer in one of several responses. I still like the idea of having an inducible phage. So maybe one response would be to have our E. coli pump out a phage for the other strain. This could be a phage for E. coli (in which case we would engineer our bacteria to lack the viral receptor) or for another strain like Salmonella. Maybe the E. coli could pump out H2O2 if it finds a clump of the drug resistant cells. Or maybe we could take advantage of the fact that during conjugation there is a physical connection between the cells. While the drug resistant strain is passing its plasmid to our engineered strain, we could make our engineered strain pass a lethal gene back (although I know conjugation in a one-way process). I like this idea because it seems to me there are several different strategies (and projects) for detecting the drug-resistant bacteria and killing them. | |||
**[[User:Doug Tischer|Doug Tischer]] 21:00, 10 May 2008 (EDT)If the drug resistant bacteria don't readily conjugate to our E. coli, we could still free their DNA into the surrounds by occasionally sending out a set of phages that would lyse the foreign cells and expose the drug-resistant plasmids to the surrounds. Again, we could put the "prophage" into the E. coli, but it would only be occasionally turned on through slipped-strand-mispairing. Once the drug resistant plasmids are in the open, it would be easier for our cells to take them up and detect. Granted E. coli aren't naturally competent, so this could pose a bit of a problem. Perhaps we could use B. subtilis, which I think is naturally competent. | |||
**[[User:Josh K. Michener|Josh K. Michener]] 02:00, 11 May 2008 (EDT): Take a look at this [http://parts.mit.edu/igem07/index.php/Rice/Project_A:_Phage_Project] | |||
**[[User:Doug Tischer|Doug Tischer]] 05:07, 11 May 2008 (EDT)Well, that's a little disappointing. However, I still think we could do them one better. I didn't like the fact that they had to modify the other strain to get a selective pressure against having the tetracycline resistance gene. I guess the project I had more in mind would be turning a bacteria into something like a white blood cell. It would have the ability to sense a foreign virulent bacteria based on plasmid genes or specific transcripts. It could then kill the bacteria in a number of ways. One might be to generate an oxidative burst with H2O2, similar to what a nuetrophil does. This would kill our bacteria, and hopefully a neighboring bad bacteria. I'm sure there are many other ways we could make one bacteria kill another if they are close to each other. | |||
**[[User:Doug Tischer|Doug Tischer]] 05:40, 11 May 2008 (EDT)Looks like there are a couple of options, if we wanted to do an oxidative burst. There are a couple of enzyme I've found besides xanthine oxidase. NADH oxidase has the advantage/complication that it is integral, 7-subunit protein. The nice thing about this is that it would pump H2O2 outside of the cell directly onto the bad cell nearby. Although, I don't know how successfully we could express a integral protein, let alone in a good stoichiometric ratio. It would definitely take a lot of playing with. Glucose oxidase looks like an easier enzyme. It's a dimeric cytosolic enzyme that consumes D-glucose and produces H2O2. Maybe we could also combine this oxidative burst strategy with protease cascade idea, to get a lot of the H2O2 producing enzyme out before the H2O2 kills the cell. | |||
**[[User:Josh K. Michener|Josh K. Michener]] 21:01, 11 May 2008 (EDT): Take a look at these <cite>tiina, stevens</cite> | |||
*Vitamins | |||
**[http://www.ncbi.nlm.nih.gov/pubmed/11676567?ordinalpos=7&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Beta carotene?] | |||
*Lactose intolerance | |||
==New ideas== | |||
===Target Specific Drugs via Bacteria Carrier=== | |||
*So something that has frustrated me about drugs is just how non-localized they are. They simply flood the entire bloodstream, hence all the negative side effects. I would be up for investigating if we can get bacteria (which would carry the drug) to locate specific targets (and thus release the drugs at specific locations in the body).... I don't know that much about blood capillaries, so I don't know if it would be possible to determine from inside the capillaries where one is in the body (maybe from solute concentration? ex. low oxygen). But I think this idea is worth investigating (at least for feasibility). | |||
**[[User:Josh K. Michener|Josh K. Michener]] 16:43, 9 May 2008 (EDT): I'm having trouble thinking of a reason that you'd use bacteria for targeting rather than a surface-coated capsule. The cancer targeting bacteria is one example, but overall I think it would be tough. | |||
**I'm not quite sure myself. Maybe if it invovles some sort of advanced calculation such as taking into account multiple factors... okay, nevermind then | |||
**[[User:Doug Tischer|Doug Tischer]] 20:52, 10 May 2008 (EDT)I had an idea just like this after our meeting last night. What if we could use a virus to target drugs to a particular cell type. I know a lot of viral capsids assembly spontaneously from their monomers, whether or not the viral DNA is present. Could we make the capsid enclose some small molecule (a stand in for an actual drug) or small peptide (like insulin) as it forms, and thus the virus would release it when it enters the target cell. We could take this one step further, and put the genes for a capsid protein from a human viruse in an E. coli under an inducible promoter (kind of like a prophage). When the promoter is activated, the E. coli starts pumping out capsid proteins which then self assembles and hopefully encloses some of our molecule or peptide. The capsid would not enlose the viral DNA, because it would not be present.Once the E. coli lyses, the virus would find its way to its target cell and release its contents. Taken one step further, this E. coli could circulate in the blood stream and produce its drug filled viruses on command. In terms of getting a peptide (like insulin) to stick to the viral capsid, we could use a sort of biotinylation system or other strong protein protein interaction. Tell me if this is just crazy or if you guys like part of it. | |||
==Older ideas== | |||
===Synthetic Biology Platform=== | |||
*So this is something that I'm quite interested in, although it might or might not be appropriate in this context. So currently, most of synthetic biology is following the platform of transmitting signals from one module to another via PoPS on DNA chains. My question is if there are any other models that we might want to explore. Or, if PoPS is the correct method, can we somehow expand the library of standard tools (inverters, etc.). Can we look through what's currently available in computer architecture and see what might be implementable in cells (not saying that computers are the right model for syn bio)? If we find a new component and implement it inside cells, although this would not be a big idea, this would certainly be quite novel and have broad uses within the scientific community. This is rather vague - I'll try to find a concrete idea of what I mean. | |||
**'''[[User:Jason R. Kelly|Jason R. Kelly]] 00:46, 9 May 2008 (EDT):''' Probably not what you're looking for exactly, but MIT folks had a brainstorming session a bit back about the [[SynBERC:MIT/Calendar/2007-8-8|most-wanted parts that aren't in the Registry.]] You could cross-ref your list against that one if you want. | |||
===Ultrafast Color Changing Cells=== | |||
*Changes within a cell are not usually instantaneous. Transcriptional and translational change can take on the order of minutes or hours to produce enough of the desired protein. Could we make this change seem faster by engineering in a cascade of proproteins? We could make the cells (either yeast or E. coli) express a GFP that had a quencher domain linked by a protease site. The GFP wouldn't fluoresce until cleaved by the appropriate protease. This event could be made sudden if the protease itself was an inactive proprotease. With several levels like this, with one proprotease activating the next, it would only take one or two molecules of an initiating factor, like IPTG to make the cells glow green. The cells would both glow green very quickly, and would be very sensitive to any traces of IPTG. Let me know what you guys think. | |||
**Could we make them change from one color to another really quickly by having different cascades for each color? Then it'd be like a single color bacteria TV or something. | |||
===Bacteriofood=== | |||
*After reviewing UC Berkeley's BactoBlood in the 2007 iGEM Jamboree, Bacteriofood could be used to produce and carry vital nutrients that can maintain a healthy human. Most useful in third world countries where food is hard to come around. Bacteria being easy to grow and maintain, could be a simple way to feed the underfed. Just trying to throw out any idea that comes across. | |||
**Some thoughts - could we make bacteria more nutritious? I.e. you'd probably need an E. coli culture plus some list of vitamins/minerals/etc. Could we come up with that list of necessary extras and then engineer E. coli to remove a couple items from the list? | |||
===Endosymbiosis=== | ===Endosymbiosis=== | ||
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**Okay, looking into this a little more, transforming mitochondria is tough. It seems that you attach your DNA to a 'microprojectile,' physically shoot it into the cell, and hope that it lands in the mitochondria. It's a 'gene gun' - I'd heard of it for transforming plants, but apparently the same is true for mitochondria. Interesting, but a little unrealistic for a summer project. | **Okay, looking into this a little more, transforming mitochondria is tough. It seems that you attach your DNA to a 'microprojectile,' physically shoot it into the cell, and hope that it lands in the mitochondria. It's a 'gene gun' - I'd heard of it for transforming plants, but apparently the same is true for mitochondria. Interesting, but a little unrealistic for a summer project. | ||
**What about yeast parasites? | **What about yeast parasites? | ||
===Taking advantage of noise=== | |||
*From an engineering perspective, noise is usually a problem we need to overcome. But in biology, a uniform response simply means that your entire population gets wiped out simultaneously (think agricultural [http://en.wikipedia.org/wiki/Gros_Michel monocultures]). Biology often hedges its bets by producing a diversity of phenotypes, some fraction of which are favored in any given environment <cite>fluct1, fluct2</cite>. Can we do the same - continually producing a range of phenotypes and allowing the environment to select the ones best suited at that moment? | |||
**I've always liked the idea of directed evolution. Usually mutation occur at random throughout the genome, but a lot of the time it seems researchers only want a few genes to change. Instead of using the time consuming site directed or random mutagenesis, could we engineer a bacteria mutation a specif portion of its genome at an accelerated rate? I'm thinking something akin to the cre-lox in which the researcher could flank the stretch of DNA to be mutated by two DNA sequences, and then an enzyme or set of enzymes would catalyze the accelerated mutation of only that portion. The ter sites and Tus proteins are normally used to terminate E. coli genome replication by slowing down and kicking off the polymerase. Maybe a toned down ter-Tus system would be enough to screw up the polymerase as it passes through, but not totally derail it. | |||
***There are mutator strains that increase the genome-wide mutation rate. Ignoring implementation, I think it would be tricky (not impossible, but tricky) to find a niche for targeted in vivo mutation. Mutator strains are generally used when you don't know what your target is. If you know what your target is, the question is what the advantage is over error prone PCR. Best I can come up with is that you might want to hit multiple genomic locations simultaneously, such that error prone PCR would be really time consuming. But those situations seem relatively rare. | |||
*"In 2006, Collins's team described engineering mutations into the control region of a gene that confers antibiotic resistance to create two strains of the yeast Saccharomyces cerevisiae , one with noisier expression of the gene, one with something more steady. Faced with a lethal antibiotic, the noisier strain survived better5. This result supports the idea that noise is a form of 'bet hedging' for cells: a population is more likely to survive in a changing environment if its members are noisy because some are likely to be making the quantity of a protein best suited to that situation. “A system that is covering more possibilities has a greater chance of survival in unpredictable settings,” says Collins." [http://www.nature.com/news/2008/080507/full/453150a.html] | |||
===CO2 Bacteria=== | ===CO2 Bacteria=== | ||
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**You're talking about photosynthesis here - fixing CO2. It's an important problem, but one that industry is already working on (see [http://www.greencarcongress.com/2005/12/greenshift_lice.html this] for instance). | **You're talking about photosynthesis here - fixing CO2. It's an important problem, but one that industry is already working on (see [http://www.greencarcongress.com/2005/12/greenshift_lice.html this] for instance). | ||
**CO2 mineralization - can we precipitate it (limestone?). | **CO2 mineralization - can we precipitate it (limestone?). | ||
==Cool outputs== | ==Cool outputs== | ||
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#holden pmid=18048927 | #holden pmid=18048927 | ||
#gally pmid=7916011 | #gally pmid=7916011 | ||
#bochner pmid=6259126 | |||
#rao pmid=16040799 | |||
#paulsen pmid=12663927 | |||
#westendorf pmid=15708311 | |||
#schultz pmid=15767015 | |||
#benson pmid=6374667 | |||
#tiina pmid=2561954 | |||
#stevens pmid=11022933 | |||
#yamaguchi pmid=17301077 | |||
#kruger pmid=12089555 | |||
#kelly pmid=9920267 | |||
#younson pmid=15209163 | |||
#iwaki pmid=2117575 | |||
#mazodier pmid=2656662 | |||
#berg pmid=1366680 | |||
#sun pmid=11707617 | |||
#gonzalez1 pmid=7775420 | |||
#gonzalez2 pmid=8157597 | |||
</biblio> | </biblio> | ||
|} | |} |
Latest revision as of 21:16, 15 May 2008
Big IdeasBioremediation (or not)
Cholesterol Degradation
Bacterial Mouthwash
Gut microbiota
New ideasTarget Specific Drugs via Bacteria Carrier
Older ideasSynthetic Biology Platform
Ultrafast Color Changing Cells
Bacteriofood
Endosymbiosis
Taking advantage of noise
CO2 Bacteria
Cool outputsPimp my E. coli
Changing shape
Motility
Stickiness
Taste
Random thoughtsA more analog device
Others
Random Number Generator
Population Variability
E(motional) coli
System Order E. coli
References
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