IGEM:Stanford/2009/Question

Response 1

 * 1) Hepatitis B vaccination through Potatoes: Hepatitis B is a fluid-transmitted viral infection that affects a large segment of the world’s population.  While there is an injectable vaccination for hepatitis B, a large portion of those affected are economically disadvantaged and thus do not have access to traditional vaccination methods.  One of the most successful solutions to this problem has been genetic engineering of food crops, namely potatoes, with non-virulent strains of the hepatitis B virus.  The only problem with this method of oral vaccination is that the proteins in the potato-hepatitis B vaccine are often denatured when cooked.  One possible project could center on the use of recombinant DNA to create heat-resistant proteins.  In the same vein, another project could focus on using E. coli to manufacture altered hepatitis B vaccines that are better suited for implantation in raw foods like bananas.  The process could then be widely applied to vaccinations for other infectious diseases like human papilloma virus, HPV.
 * 2)  Synthetic “Lab-on-chip” cell: A “lab-on-chip” or LOC is a device that integrates one or several laboratory functions on a single chip. The lab-on-chip device is particularly useful in microfluidics where “wet” chemistry on a small scale needs to be conducted frequently.  However, LOCs cannot be placed in biological systems, like organs, because of biochemically incompatible dopants and base metals.  Hence, one possible project could focus on converting a bacterial cell like E. coli into a synthetic “lab-on-chip” that can be introduced into the body.  This could have wide implications, for example, in the creation of insulin in vivo given particular starting materials.
 * 3) Energy Harvesting E. coli bacteria:  A recent article in Technology Review already indicated that minor changes in the DNA of E. coli bacteria can allow them harvest light instead of sugars to create energy.  A possible project, thus, could look at increasing the energy efficiency of such bacteria by introducing certain genetic modifications that enhance the absorbance power of the E. coli strain.  Another possible project could look into procedures by which the E. coli-harvested light energy could be converted to other, more useful forms of energy.

Response 2
One of my favorite biological enigmas concerns cell differentiation: at what point are cells terminally differentiated? For a cell that is far along in a specific developmental pathway, how much plasticity or flexibility does it have to change course and enter a different pathway? I have been curious about this since taking biology in high school, and learning about helper T cells from working in an immunology lab has only amplified this curiosity. (Research about highly inflammatory Th17 cells—a recently discovered subset that I am rather fond of—suggests that the lines between this subset and two others—Th1 cells and Tregs—are blurred even though it was once thought that the pathways shared a common progenitor but were mutually exclusive. Findings about this, and about T cells that express intermediate phenotypes of these supposedly antagonistic and separate lineages completely blew me away.)  I don’t think there is really any way to answer this question except by on a case-by-case basis, and specifically for the case of Th17 cells and Tregs, for instance, I think it would be interesting to bioengineer cells so that even when they appear to be terminally differentiated, they are highly responsive to pro- or anti-inflammatory signals in the surrounding environment and can quickly enter alternative pathways and differentiate into a different and supposedly antagonistic lineage. I feel that clinically such a bioengineered cell would be interesting, too, because the balance between Th17 cells and Tregs has been implicated in the disruption of immune homeostasis and emergence of autoimmunity.

Learning about the current medications to the disease I’ve been studying (sJIA, or juvenile arthritis) has frustrated me and raised another question for me: why are all the therapies so focused on mitigating and preventing symptoms instead of trying to take a more proactive role in trying to cure the disease? Instead of just abrogating inflammation to curb joint destruction, why do none of the medications I’ve learned of attempt to rebuild these destroyed joints? I believe that synthetic biology has the potential to create a therapy that is more focused on controlling joint destruction, rather than simply responding to it. Chondrocytes, the cells that maintain articular cartilage, cannot repair extracellular matrix injured by inflammation; but perhaps they could be bioengineered to do so if genes whose products rebuilt the ECM were transcribed in response to certain anti-inflammatory molecules, which would serve not only to activate these genes, but also to curb the inflammation in the setting of the joint.

I realize that my response to this question seems deeply rooted in immunology, but though I find the immune system fascinating, I hope that it does not seem that I am averse to entering a new field of study. Sometimes I feel torn—I would enjoy continuing in immunology, but I would also love to sample some different fields in biology during college.

Response 3

 * 1) E. Coli for to help solve diagnosis problems, eg. HIV/AIDS. E. Coli are found predominantly in the lower intestinal regions of the human body, and provide an integral contribution to the body’s need for vitamin K. Is it possible to engineer an E. Coli organism, using DNA recombinant technology, that is more dominant that the body’s natural supply of E. Coli, so that once introduced into the body, its progeny will eventually replace all of the original E. Coli? This new strain could be engineered to produce a non-toxic, non-absorbable indicator under specific conditions, such as when the human body is infected with some sort of pathogen. Perhaps when the pathogen is present in the body, the gene that encodes this indicator can be activated, and a patient’s stool sample can be analyzed for the presence of this indicator.
 * 2) Malaria: Malaria is transmitted when a mosquito bites an already malarias person, obtaining the parasite through the blood, and bites another victim. What if male mosquitoes could be infected with a bacterium. This bacterium could have a gene that produced a toxin upon activation by a certain particle normally found in human blood. If male mosquitoes were infected with this bacterium, they would pass it to females, who upon feeding on human blood several times, would be killed by the toxin. This would ensure that mosquitoes would have sufficient time to reproduce before dying, thus transmitting this bacteria. The toxin would hopefully halve the normal lifespan of a female mosquito, reducing her number of feedings significantly.
 * 3) Eutrophication of water habitats: While eutrophication occurs naturally, man-made phosphorus compounds are aiding the process, and large numbers of natural habitats are dying. Algae bloom when exposed to excess amounts of phosphorus, simultaneously using up all the oxygen in its environment. Is there a bacteria one could bioengineer that is completely anaerobic, but that prefers phosphorus as its fuel, perhaps some archaebacteria? It could keep phosphorus levels in check without taking a toll on the inherit oxygen levels of a water ecosystem.

Response 4

 * 1) Cleaning smog using photosynthesis-powered bacteria: Pollution is a major problem in metropolitan areas, and most measures taken against pollution are pre-emptive.  As for solutions to clear up pollution after the fact, however, few exist.  Pollution in mediums such as water is somewhat easier to collect, but air pollution control devices are limited to immediate-action devices, such as a filter over an exhaust.  While no effective solution to general air pollution exists, modifying bacteria to neutralize certain pollutants could be promising.  There are already several known types of bacteria that are able to oxidize compounds in the environment.  Hazardous pollutants like nitrogen oxides and sulfur oxides could be oxidized into harmless nitrates and sulfates.  Bacteria able to oxidize certain pollutants in the air, powered by an energy source like photosynthesis or even just oxygen and carbon dioxide (obtained through DNA splicing or another method), could be very effective in certain polluted areas.
 * 2) Digital storage using larger-than-binary bits: Being into computers and other gadget-ey stuff, I follow hardware development quite a bit.  Hard drives started as – and even up until now remain – based on a basic binary code made of bits.  Each bit can store one of two options: 0 or 1.  Essentially, every aspect of digital computing is based in binary code.  Currently, hard drives are made up of many, many bits, controlled by magnets.  But imagine if, instead of physical metal bits, hard drives were made of biological bits – bits that can store more than just two different options.  Even neurons can respond to more than one type of stimuli; there are many biological materials that could take more than two different states.  Even a biological bit that could take just four different states would mean only having to use one half of the number of bits to store the same information.  Of course, computer code as we know it would have to be at least partially revamped.  But if storage or storage accessibility become problems – and they are already, almost – basing a digital system on biological higher-order bits would be an effective solution.
 * 3)  Creating organic, biodegradable plastic using modified plants: Today, problems exist with how plastic is manufactured.  Derived from petroleum, which is not a renewable resource, commercial plastic is also hard to dispose of.  There are certain bacteria which are known to be able to produce an organic type of plastic.  However, there are limitations to using bacteria, namely that bacteria have both specific environmental demands and nutritional demands.  Now think plants.  Plants represent a wonderful system of energy transformation, converting sunlight (a practically renewable resource) into (usually, for example) a product like fruit.  What is there to keep a plant from producing something else?  Splicing DNA from plastic-producing bacteria with plants in a fashion that causes the plant to grow bioplastic instead of, say, certain parts of seeds or fruits, would provide a very renewable way to produce environmentally safe plastic – solving two problems with today’s manufactured plastic.
 * 4) Anti-assassination bacteria: Ok, so this isn’t really one of the three ideas, but how cool would it be to have bacteria living in your mouth that scan for a certain chemical?  It wouldn’t be hard to find/create bacteria that sense elements that indicate a possible poison and then subsequently react to the stimulus.  So if somebody tried to poison you with cyanide in a drink, you’d drink it unknowingly but then your CN-species would sense the cyanide and then, say, heat up or otherwise let you know that you’re being poisoned.  If they were advanced enough they could even perhaps turn the compound into a less harmful compound.  I think I’m dreaming and this stuff probably isn’t even remotely feasible, but it still sounds cool!

Response 5
Called the first postmodern pandemic, AIDS currently affects over 33 million people. Unfortunately, although preventing the spread of HIV seems very feasible from a biological perspective (i.e. HIV is not capable of airborne transmission, nor can it be transmitted by blood-sucking insects such as mosquitoes), there are many social hurdles that hinder AIDS prevention. One of the primary hurdles is that people infected with HIV may not suffer symptoms of AIDS for several years, and so are at risk of spreading the virus unknowingly to people around them.

One possible solution to this problem may be to genetically engineer a non-pathogenic microbial organism that, upon recognizing an HIV antigen expresses proteins that synthesize in excess a highly colored compound, such as beta carotene. Thus if a person carrying these microbes gets infected with HIV, his external appearance would turn a shade of color (in the case of beta carotene an orange hue). Of course such an obvious indicator could lead to problems of stigmatization and discrimination, so more advanced versions may utilize microbes that migrate to a particular area under the skin, such as underneath the palms. When considering the economics of this solution, perhaps these microbial indicators could be integrated through the food or water industries. Finally, this technique could be extended to other pathogens that exhibit a period of latency (initially asymptomatic).

Chemotherapeutic cancer treatments are often highly toxic to the body, and specificity to tumor cells is a major barrier to creating effective cancer drugs. '''A possible solution may be to develop a microbe with a gene controlling the synthesis and release of a deadly cytotoxin. H'''owever, the genetic sequence coding for this gene would be constructed out of modified DNA nucleotide bases that can only be transcribed by special RNA polymerases (i.e. artificially engineered polymerases), and the microbe would be designed without these special polymerases by default. Thus by itself the microbe would be harmless to the body’s cells.

The treatment would then involve permeating the body with these microbes so that they are present among the cells of the body, including any tumor cells. Next, the special polymerases would be delivered only to the tumor cell regions, activating the transcription of the cytotoxin gene and killing the surrounding tumor cells. To stop the microbe from continuing to express the cytotoxin gene after the tumor cells are all killed, the microbe could be engineered to express a limitation protein that destroys the special polymerases after a certain amount of time. Another possibility may be simply to deliver into the treatment region an enzyme that denatures the special polymerases.

As major droughts strike more frequently around the world, increasing attention has been given on finding viable solutions to the water crisis. The desalination of water by evaporation is one method that is being adopted by several nations. A possible way to accelerate the process of evaporation may be to design microbes capable of breaking down cellulose and which express the uncoupling protein UCP-1. Placing these bacteria in water and feeding them cellulose would therefore cause them to generate heat that would augment natural rates of evaporation. Economically speaking, the cellulose source could be non-recyclable papers and other plant-derived products.

Response 6
The question of the origin of life, its first appearance on Earth, constantly occupies my mind. I have come across a number of explanations to abiogenesis, ranging from creation theory to the theory of spontaneous generation, neither of which is entirely satisfying. So if I was to phrase my curiosity into a question, it would perhaps/thus run, “How did living tissue first emerge on Earth from inorganic nitrogen and carbon compounds?”

With the new field of synthetic biology, artificial bimolecular systems are now being designed to mimic biochemical reactions of a living cell. It is through taking a system apart, redesigning each part, and placing the mimicked parts together to recreate the system that synthetic biologists are able to not only understand but to recreate a biological system. In theory, the same methods could be applied to explain the origin of life—given the physical conditions during which life emerged, and the raw material chemical compounds that early life consist of, organic molecules can be recreated through artificial design. Only when we, as scientists, are able to recreate life from inorganic compounds, can the question of the origin of life truly be answered.

Response 7
What makes it so hard to target cancer and HIV infected cells? Most of the current drugs and treatments on the market tend to have many side effects such as chemotherapy. Is it possible to engineering a virus to specifically target a cancer or HIV infected cell? Such examples can be seen here:

Use of genetically engineered phage to deliver antimicrobial agents to bacteria: an alternative therapy for treatment of bacterial infections. PMID: 12654662

Engineered Virus Targeting HIV Infected Cells PMID: 11364688 (Short Summary)

Response 8

 * 1) One idea that I have thought about is the creation of a synthetic stem cell. I think that if we could isolate the genes for differentiation from an embryonic stem cell and put them into an actively dividing cell, then we would create numerous synthetic stem cells. Or by putting the gene in 	just a normal cell and then adding the right regulators and enzymes, we would "force" the cell to differentiate into almost any cell necessary. An even better idea would be to take the growth genes from a cell that needs 	to grow and divide rapidly and numerously, such as the red blood cell, and put them into a stem cell so that now the stem cell grows and divides at a much faster pace. If this could work, it would have huge implications in the medical field and treatment industry.
 * 2) From what I have read, a major neurotransmitter in the brain is acetylcholine. This chemical is involved in learning and memory storage and plays a role in the memory loss associated with Alzheimer's disease. 	It is not made from amino acids, but rather from choline, which is a lipid-like substance that you can consume to boost acetylcholine production. However, in order to synthesize it, your brain needs the key enzyme acetyltransferase. Decreased levels of this enzyme lead to memory loss. My idea for a project comes from this. If we could engineer a bacteria which codes for the production of acelyltransferase, this 			synthetic enzyme  could then be used as a "supplement" for those facing memory loss or malfunction. Or we could create a system in which the 	bacteria create the regulators necessary to turn on production of the enzyme in the brain.
 * 3) My third idea once again pertains to the human body.  It sounds like a neat idea and with brainstorming I think it may work. One of the main causes of cancer, aging, and body damage in general is the 			presence of free radicals in the body. Antioxidants help our bodies by interacting with these free radicals and getting rid of them and we can get some antioxidants in our diets. However, I think that we could engineer a more efficient system in which we target the free radicals, gather them, and "extinguish" them from the body. We would have to create a chemical and/or a chemical pathway that is attracted to the unpaired electrons. We could possibly then use the charge potential  and interaction to help drive our system. This would be a very helpful way to improve one's health and prevent internal damage.

Response 9
1.	E. Coli for to help solve diagnosis problems, eg. HIV/AIDS. E. Coli are found predominantly in the lower intestinal regions of the human body, and provide an integral contribution to the body’s need for vitamin K. Is it possible to engineer an E. Coli organism, using DNA recombinant technology, that is more dominant that the body’s natural supply of E. Coli, so that once introduced into the body, its progeny will eventually replace all of the original E. Coli? This new strain could be engineered to produce a non-toxic, non-absorbable indicator under specific conditions, such as when the human body is infected with some sort of pathogen. Perhaps when the pathogen is present in the body, the gene that encodes this indicator can be activated, and a patient’s stool sample can be analyzed for the presence of this indicator.

2.	Malaria: Malaria is transmitted when a mosquito bites an already malarias person, obtaining the parasite through the blood, and bites another victim. What if male mosquitoes could be infected with a bacterium. This bacterium could have a gene that produced a toxin upon activation by a certain particle normally found in human blood. If male mosquitoes were infected with this bacterium, they would pass it to females, who upon feeding on human blood several times, would be killed by the toxin. This would ensure that mosquitoes would have sufficient time to reproduce before dying, thus transmitting this bacteria. The toxin would hopefully halve the normal lifespan of a female mosquito, reducing her number of feedings significantly.

3.	Eutrophication of water habitats: While eutrophication occurs naturally, man-made phosphorus compounds are aiding the process, and large numbers of natural habitats are dying. Algae bloom when exposed to excess amounts of phosphorus, simultaneously using up all the oxygen in its environment. Is there a bacteria one could bioengineer that is completely anaerobic, but that prefers phosphorus as its fuel, perhaps some archaebacteria? It could keep phosphorus levels in check without taking a toll on the inherit oxygen levels of a water ecosystem. How can computer science be used to model “cross-talk” between BioBricks?

How could a reliable “network protocol” be created between BioBricks to allow them to communicate with each other?