Elizabeth

== =about me= ==Hello I'm Liz. Or Elizabeth, Lizzy, Franson. i don't really have a preference except under no circumstances may you call me Betsy. i live in a town in the northern suburbs of Chicago that is so preposterously small its technically a village. so lets just say i live in Chicago(i spend most of my time there anyways).== ==not entirely knowing what synthetic biology was, BLI immediately caught my interest. its seemed to me to be a nice marriage between biology and engineering. i am always exited to see two things i enjoy combined into something new(except for something like ice cream and sushi, but food aside, it works very well for intellectual endeavors!). in addition i love to see courses offered in subjects that are cutting edge as they are usually dismissed as "too new" for students, which is ironic because young people are often the ones who find it easiest to pick up new things. i wanted to explore a subject with uncharted territory and lots of potential possibilities so synthetic biology seemed perfect.==

i have been interested in science since before i had a concept of what the world even meant. as an only child my parents always tried there best to shelter me from the world i was so curious to explore. at the age of eight my parents storys of santa clause were starting to sound a bit far fetched so i decided to obtain "evidence" of his existence by constructing an alarm system including a tripwire that ran the length of the living room and a hidden intercom. i have always been fascinated with evolution physics and any other subject matter that could give me insight into the world. i found i had a natural talent for biology and received the highest grade in my class last year in ap bio.

=
as far as other school experiences go, i **received** **a 101** **average** **my junior year(let's just ignore my** **sophomore** **and freshman grades). i have rowed for my schools crew team, though lately theater has taken up much of the time i used to devote to rowing. i have been in** **several** **school plays, gone to theater fest, participate in improv, and am going to be a thespian board member this** **coming** **year. i am a clavius scholar and part of the mentor leadership program at my school. some** **academic** **competitions i have participated in are science** **Olympiad** **where i built a functioning robot in one night and** **received** **second place in the designer genes event, and the WYSE test were i** **received** **first place in biology and our team won third at state. i also participated in a** **Chinese speech** **competition and do dramatic interpretation for speech and debate. when im not doing any of that i** **manage** **to make a few meetings of anime club,** **Chinese** **club, adventure games club, and creative writing club.** ======

outside of school i am a black belt in karate. i **volunteer at my church and came back from a week long mission trip in Joplin, Missouri before i came here. i like to draw, read, write and cosplay at anime and comic conventions. in addition to that i have an etsy store were i sell things made from recycled materials and am teaching** **myself objective c to** **develop iPhone** **and** **iPad** **apps. i make things like dresses out of duct tape, solve** **Rubik's** **cubes and am an** **amateur** **model. i also climb EVERYTHING i see including but not limited to trees, walls, fences, poles, play structures, and statues if** **permitted. i still drag my friends to playgrounds and pretend to be a child again.** though im not sure what my future holds i have the mind of a scientist and the heart of an artist and i hope to go into a field that utilizes both my logic and creativity.

p.s yes, I know, i'm supposed to capitalize the beginnings of sentences and the letter I. but because it does not interfere with comprehension (did you even notice until now?), im writing this as it it much more efficient and less tedious than going back and recapitalizing the beginning of every sentence. to all the grammar sticklers who read this, thank you for your understanding.

= design project = = = = = =Let Them Eat Grass= how bacteria, cows, and synthetic biology can help solve world hunger

On the first day attending my synthetic biology camp we were immediately
=== discouraged to attempt to cure cancer. With that topic no longer an option it seemed reasonable to attempt to solve world hunger instead. Utilizing synthetic biology symbiotic bacteria could be designed to enable humans to digest plant Cellulose ,the most abundant form of organic matter and aid in the fight against hunger and poverty. ===

Hunger on a global scale is defined as "the want or scarcity of food in a
=== country". Scarcity of food leads to malnutrition or under nutrition which can cause lack of energy, weakened immune systems, underweight, cognitive impairment poor growth, muscle loss, bloated stomach, osteoporosis, organ failure and death. === === Hunger and poverty are relentlessly interconnected problems. The effects of hunger such as fatigue sickness and nervous system impairment make it difficult to work and earn a living consequently exacerbating the situation. === === time and energy must be spent acquiring food instead of working for income which could be used to improve living standards acquire necessities or fund education. Thus hunger hinders the escape from poverty. === === Hunger is a major global problem not only because of its detrimental consequence to individuals and society but because of its overwhelming numbers. It is estimated that between 870 million and 1.02 billion, are victims of hunger and make up 15% of the people in developing nations. Nearly half of the deaths of children are due to hunger related causes. In addition the number of hungry people has increased by 46 million in the past 10 years and the numbers are not expected to improve. While the demand for food is expected to increase by nearly 50% crop yields in many poor and developing countries is expected to plummet by more than 25%. ===

The conundrum of hunger has endured in human society since its creation thousands of years ago, but a potential solution can be found much older species.
=== For thousands of years herbivores have been living off a diet of leaves grass and plant matter that humans are incapable of digesting, however they are not actually the ones doing the digestion. Cellulose, a major component in plants is actually indigestible by any vertebrae creature. Herbivores such as cows sheep and horses rely on symbiotic bacteria in there gut to secrete enzymes to hydrolyze cellulose into glucose in while the host allows the symbionts to inhabit the gut and share a portion of ingested nutrients. In some animals bacteria are responsible for digesting materials that account for up to 80% of the creature’s energy. If even a portion of this ability could be replicated in humans, material that has previously been regarded as waste could become a nearly unlimited food source. ===

Cellulose is the most abundant source of organic carbon and makes up 30
=== to 70% of any type of plant. Vegetables such as celery are low in calories because of their high cellulose content. Instead of excreting and wasting cellulose humans could utilize cellulose as a source of alternative energy. === === The proposed bacteria would secret the enzymes necessary to hydrolyze cellulose into glucose and render it digestible to humans. With new resources available the demand for food would be eased and hunger and poverty substantially lowered. ===

= Competition = === The major solution proposed to fight hunger, particularly in developing countries, is development of agriculture. The goal is to establish self sufficiency so that people can provide food for themselves and potentially earn a profit. The proposed technology is not so much a competitor as much as collaborator. If people could consume nonagricultural plants and glean more energy from the food they have, they could work more efficiently and would be less dependent on crops for sustenance. These excess crops could be sold for profit and be key to escaping poverty. ===

Several research endeavors have been geared towards engendering bacteria to degrade cellulose for human consumption.
=== However almost all of the bacteria convert cellulose in a lab setting were it would have to be sold and distributed. this technology would not be nearly as beneficial to those who could not afford to buy this new compound and who need its benefits most. ===

= Design = === Structurally, Cellulose is very similar to starch. however Cellulose is made of β1→4 linked D-glucose as opposed to starch which contains alpha bonds. The cellulose hydrolyzing bacteria would produce enzymes to convert cellulose to glucose and inhabit the human intestines. While this proposal may seem unusual humans are actually already hosts to a multitude of bacteria which provide us with approximately 30% of our nutrients. === === To hydrolyze cellulose bacteria use enzymes called celluase to break the beta bonds converting cellulose to cellulobiose and then glucose. There are many different types of cellulases and mechanisms used to employ them. The most simple mechanism is to secrete free cellulases Ito the environment. For this design I have chosen a slightly more complex but more effective mechanism. ===

Cellulosomes consist of cohesins dockerins and an anchoring protein.
=== Cohesins organize and structure the cellulolytic subunits into a multi-enzyme complex. they have sites with a high affinity for binding to dockerins and a cellulose binding molecule which attaches the cellulosome to the substrate. The also contain x proteins of unknown function. The module anchors the catalytic subunits to the scaffoldin. The diversity of dockerins allows for multiple enzymes to degrade cellulose and other insoluble plant materials. The anchoring protein attaches the cellulosome to the cell with slh protein. ===

While the cellulosome is more complex and not all its functions are know it
=== offers several advantages over secreted cellulases. Instead of secreting a few types of cellulase cellulosomes have evolved to completely unravel plant structures and can degrade cellulose hemi cellulose and lignin, a tricky substance That provides structured and protection for plants. Cellulosomes are much more efficient than free cellulases and require a low ph of 5 while cellulosomes have been shown to act more efficiently in a ph of 7 which is approximately the same acidity of the human gut. ===

[[image:bli-biotech-research/Image 2.png width="256" height="218" align="right"]]
=== The protein HPr which then phosphorilates the EllABC complex. As glucose is uptaken it is phosphorilated by EllB producing glucose 6 phosphate. fructose 6 phosphate formed in glycolysis activates HPrK which phosphorilates HPr. HPr-Ser-P binds to repressor CcpA which inhibits gene transcription, and allows transcription of the cyspin genes. ===

=== The red transmembrane complex has an external cbm and an internal anti-σ peptide domain. When off the anti σ domain is bound to the blue alternative σ factor and it is inactive. When a polysaccharide, in this case cellulose binds to the cbm the anti-σ domain releases the σ factor Which interacts with RNA polymerase. RNA polymerase promotes transcription of σ-dependent promoters and the subsequent genes, in this case cellulosomal genes, as well as the rsgI/rsi24C gene. ===

=== There are many types of cellulosomes. For this initial model I chose Genes fom the bacteria clostridium thermocellum, a bacteria native to the bovine digestive track,. However other cellulosomal genes should work as well. === ===

===

= Expected results = === When put together inside the bacteria, these operons for an efficient cohesive(no pun intended) structure to degrade cellulose only when glucose is absent and cellulose is abundant. This way the cell does not waste energy producing cellulosomes when there is nothing to degrade and if the host can fulfill its nutritional needs with glucose the cell effectively becomes invisible until needed again. While most plants do not consist of purely cellulose or purely starch, the relative amounts of each acting upon thousands of bacteria will hopefully allow the net response to reflect the relative amounts of each substance. While there will be some inefficiency, the main goal is to have the bacteria produce more sugar from cellulose degradation than it consumes and provide the host with a positive amount of net glucose. This would allow people to utilize alternative food sources and become less dependent on traditional staples. ===

= Advantages = === While many have considered cellulose degrading bacteria for the purposes of bio fuels Few have considered its possible applications as fuel for humans. Of those few none have seriously considered the advantages the bacteria could have outside of a lab setting. Instead of degrading cellulose, constructing glucose polymers and distributing them publicly, internal bacteria would allow humans to directly extract more energy from the food they consumed. Bacteria unlike Cellulose polymers can self replicate. A small amount of consumed bacteria could grow to significant numbers and spread similar to most symbiotic bacteria. This would mean the bacteria would also be able to colonize the gut of infants from there mothers and those the person comes into close contact with. The concept of wanting to spread bacteria may seem difficult to swallow, however this process is constantly happening without our knowledge and is actually beneficial to both our gut and our immune systems. This ability would essentially solve the problem of distribution. Once a person has ingested the bacteria they will forever gain the ability to digest cellulose. The bacteria require no special maintenance and will seem almost nonexistent to the host other than providing extra nutrients. This would allow people to have greater chances of survival and economic success which could improve the lives of people and the social structure of entire nations. ===

= Problems = === Potential complications that could arise are much more likely to result in the bacteria being ineffective as opposed to dangerous. The main challenge will be to engineer the bacteria to degrade cellulose efficiently enough so that the net product of glucose is positive and enough to significantly impact energy. ===

=== In addition The environment of most cellulose degrading bacteria is slightly different from the human digestive track. Ruminants often have longer digestive tracks additional organs and different symbionts to aid in digesting large amounts of cellulose. It is unknown how the new bacteria will interact with other microbes and how this will affect the survival of itself other microorganism a and the total health of the digestive track. === === While it is unlikely to become the next mersa precautions should still be taken to contain the bacteria within a streak lab environment until it has been fully developed and tested. Standard laboratory measure used when normally dealing with bacteria such as hand washing and proportion disposal of bacteria should be taken. Extreme containment measures would be unnecessary. Environmental impact should be minimal as the bacteria do not produce any toxic compounds. Even if the bacteria escape into the environment they would die almost instantaneously as they are anaerobic. They could possibly upset gut flora in live test subjects but preliminarily testing would be done to minimize that chance. Considering the worst case scenario is a stomach ache these bacteria are relatively harmless and low maintenance in terms of containment and there is no reason why safety concerns should prevent them from being developed. ===

= Testing = === The bacteria could be difficult to test in a lab setting as it is difficult to culture symbiotic bacteria outside of a host. Conditions would have to be replicated and when determined safe live hosts would be needed for testing. Assuming the gene regulation is effecting much of the testing will involve attempting to improve the efficiency of the cellulosomes. They are many different types of cellulases and cellulosomes found in different organisms and only testing will determine which combinations work best. Some companies in the bio fuel industry have gone as far as making designer cellulosomes which are transcribed from entirely synthetic genomes and utilize the best aspects of different cellulase enzymes. The more efficient the bacteria are made the greater power they will have not only to break down not only cellulose but also one of humanities greatest dilemmas. ===