IGEM:Harvard/2007/Brainstorming/

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Some great ideas here.
Some great ideas here.
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I wanted to follow-up on some discussions of gut flora.  I recently learned that E.coli is actually not one of the dominant inhabitants of the gut --- just one of the most easily cultured (see http://en.wikipedia.org/wiki/Gut_flora and references therein).  I'm not usually a big wikipedia citer, but in this case is does an excellent job of summarizes and presenting specific citations.
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I wanted to follow-up on some discussions of gut flora.  I recently learned that E.coli is actually not one of the dominant inhabitants of the gut --- just one of the most easily cultured (see http://en.wikipedia.org/wiki/Gut_flora and references therein).  I'm not usually a big wikipedia citer, but in this case is does an excellent job of summarizing and referencing specific citations.
Re a suicide program.  A number of groups have developed methods for this.  Check out work by Arnold and colleagues on "population control".  Death genes abound, so putting them under the control of some external "switch" could be one possible course of action.
Re a suicide program.  A number of groups have developed methods for this.  Check out work by Arnold and colleagues on "population control".  Death genes abound, so putting them under the control of some external "switch" could be one possible course of action.

Revision as of 13:07, 23 April 2007

Some great ideas here. I wanted to follow-up on some discussions of gut flora. I recently learned that E.coli is actually not one of the dominant inhabitants of the gut --- just one of the most easily cultured (see http://en.wikipedia.org/wiki/Gut_flora and references therein). I'm not usually a big wikipedia citer, but in this case is does an excellent job of summarizing and referencing specific citations.

Re a suicide program. A number of groups have developed methods for this. Check out work by Arnold and colleagues on "population control". Death genes abound, so putting them under the control of some external "switch" could be one possible course of action. See: You L, Cox RS 3rd, Weiss R, Arnold FH. Programmed population control by cell-cell communication and regulated killing. Nature. 2004 Apr 22;428(6985):868-71.

Great work, Jagesh


After thinking about the legal and practical implications of using bacteria for jobs such as detoxification, biosynthesis of drugs, and detection of toxins, I realized that it might be useful to have some sort of "off" switch - a way to quickly and efficiently kill the engineered bacteria without using antibiotics or anti-septics. It might not be useful in the strict sense since engineered bacteria are likely to be maladapted for natural environments, but it might put people at ease.

There are any number of methods of doing this, but the easiest is probably adapting a bacteriophage that integrates its genome into the E. coli genome - perhaps the lamba phage. From there, we would need to play with the promoters so that we are able to switch the virus to the lytic part of its life cycle at will. We could either switch out the wildtype promoters and install an entirely new promoter, or we could tamper with the lambda promoters. More on this later

Alexander


I hope you'll consider presenting more on this on Monday. Even if not, the thought is intriguing. I understand the hesitation to use antibiotics (presumably, resistance?), but my presentation on adaptamers tomorrow might have lightly-related ideas - since the potential uses of adaptamers are quite broad, we could potentially target drugs or bacteria-killing substrates to the cells. As you said, the legal and practical implications would probably cause me to discard the idea, but at least it's tangentially related.

Stephanie



I wanted to put forth an idea -- vitamin production & microbial therapy. The idea comes from the fact that vit B producing microbes inhabit the ruminant gut so these animals almost never have B-deficiency. But for humans, without a proper diet, we end up getting diseases like Beriberi.

  • the other thing is the bioavailability of these vitamins whether we ingest them as food or as pills -- 'microbial therapy' could solve this by coupling these production loops in our engineered bacteria

One way to put an end to this could be synthesizing bacteria that can inhabit the human stomach and produce vitamins of all kinds. ...that's the idea

Response (Stephanie): I really like this idea. I wonder what potential limitations there are, etc. Did you find any interesting readings on this?

Response (Alex): The great convenience of this is that E. Coli is not only a well-understood model organism, but also one of the most abundant gut flora. If we can actually introduce genes for vitamin synthesis, this is actually feasible. The only problem is that the genes which would do our vitamin synthesis would leach energy from the bacteria and make them less competitive than the native E. coli. Hence the native bacteria would eventually crowd out the modified ones.h


Project Ideas 3/19/07

Brainstorming with Sammy, Alex, Shaunak, Stephanie, Mingming, Perry, and George. TFs and Advisors in attendance Nick, Mike, Harris, Tamara, George Church, Jagesh Shah, William Shih, and Alain Viel.

Biological Based Fuel Cells

Bacterial that Respond to (by fluorescence) or Degrade Plaque

Viruses as a Transfer Mechanism

Engineering E. coli to Resist Mutations
--The intention is prevention of evolution that would ruin biological parts; however, we recognize that directed evolution is a useful tool in 'discovering' potentially useful parts and mutations. http://www.seas.harvard.edu/projects/weitzlab/Jeremy%20web%20page.htm

Cellulose to EtOH in Algae or other system

""~~Some Papers on this Subject (added by SAV, feel free to add more)11:22, 2 April 2007 (EDT)""

Lynd, Zyl, et al. "Consolidated bioprocessing of cellulosic biomass: an update" Current Opinion in Biotechnology 2005, 16:577-583
---This paper gives a pretty good overview of research into consolidated bioprocessing of cellulose into ethanol, and some of the main problems as well. If we're interested in looking at fuels, this is definitely a good paper to look at.

Jeffries, Thomas. "Engineering yeasts for xylose metabolism" Current opinion in biotechnology 2006, 17:320-326.
---This paper looks at turning xylose into ethanol via yeasts, and recent results in this field of research. If we think we might not want to use bacteria, this is a good overview.
Sticklen, Mariam. "Plant genetic engineering to improve biomass characteristics for biofuels." Current Opinion in Biotechnology 2006, 17:315-319
--Looks at problems from biomass cellulose, such as lignin, and current research into ways to treat it. Also looks at other ways to engineer plants. I think less relevant for us, but still interesting as a way for getting a feel of some of the issues surrounding biomass cellulose


Fatty Acid Production and Degradation for Energy

Molecular Motors

Sequestration of Toxic Compounds by Bacteria (arsenic)

Bacterial Surface Expression

Vascular Tissues

Artificial Vascularization in Bacterial Biofilms

Bacterial Biosensors (Detection in the Environment) (Water Samples)


Project Ideas from Second Meeting (04/05/07) Additional notes added by Stephanie; please contact her with questions.

  • Selection mechanisms for key/lock riboregulators (see 2006 Berkeley Project)

- Though sequence complementary is necessary, which allows little variation in that region, the rest of the RNA might differ
- The RNA acts as a "key" to release the lock; only when both are present, allows for expression
- This can allow for creation of networks, if the expression "unlocked" is for another key
- Monitored by Red Fluorescent Protein, experimentally
- Advantage = fast response
- Can be used for either activation or inhibition
- Suggestion: look into the Duke group: human encryption

  • Biofuel & light sensitive proton pump (see background reading #3) (Pseudomonas Putida for exportation of short chain alkanes)
  • Powering medical devices

- Bacteria that can extract energy from sugars in blood and convert these to electricity
- Question posed: how often do the devices need energy? A: Depends on specific devices
- Related idea: implantable devices that release, or even synthesize, drugs

  • Artificial cells
  • Use of psuedomonas putida? (bacterial strain)

- High tolerance to many saturated alkanes (can we get it to form octane?)
- Issue: export vs. metabolism

  • Quorum sensing and biofilms
  • Mirror image proteins
  • Nonribosomal synthesis of proteins
  • Radon sensor (practical considerations of working with Radon)


Short discussion of project logistics: rather than attempting to tackle multiple projects at once (as we will tend to be overambitious!), perhaps we can propose a sequence of experiments that we would like to attempt over the summer. We should treat these as 'checkpoints' and finish one before proceeding to the next.

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