Team:UIUC Illinois/Project/Overview

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<p class="center"><b>Project Overview</p><br><br></b>
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<p class="center"><b>Project Overview and Abstract</p><br><br></b>
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Our project, Cardiobiotics, works to prevent cardiovascular disease by reducing the metabolism of dietary l-carnitine within the digestive system.  This made possible through the use of three biological parts that fulfill two very important functions: the take-up and the break-down of L-carnitine.<br><br>
 
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The take-up of L-carnitine into the cell is facilitated by two biobricks: the <a href="http://parts.igem.org/Part:BBa_K1205002">CbcWV Uptake Protein</a> and <a href="http://parts.igem.org/Part:BBa_K1205001">CaiX Carnitine Carrier Protein</a>.  This combination of proteins form a membrane-bound carnitine uptake system for bringing greater amounts of L-carnitine into the cell.<br><br>
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        Cardiovascular disease (CVD) has been the leading cause of death in the United States for over twenty years and is becoming a severe global health issue. CVD is highly associated with the buildup of plaque in arteries, a disease known as Atherosclerosis. Trimethylamine N-oxide (TMAO) is a known proatherogenic substance, and is abundant in carnivorous humans and those who consume energy drinks. It is the goal of the University of Illinois at Urbana Champaign (UIUC) iGEM Team to lower the amount of TMAO found in such individuals and therefore reduce the risk of atherosclerosis for those afflicted.TMAO is produced when the gut microbiota process the amino acid derivatives L-carnitine and choline. These metabolites are abundant in red meats and energy drinks, and are important bodily compounds; however, humans are intrinsically capable of producing the necessary amounts. When these substances are consumed, specific gut bacteria convert L-carnitine and choline into a harmful byproduct trimethylamine (TMA.) To protect itself, the liver oxidizes TMA into TMAO. We are creating a probiotic to outcompete the gut bacteria for L-carnitine and choline to effectively lower and ultimately remove the atherogenic activity caused by TMAO. Pseudomonas aeruginosa is a bacterium with novel adaptations that enable it to uptake L-carnitine as a sole source of carbon and nitrogen. These genes have been selected for and are being tested in various Escherichia coli.
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The break-down of L-carnitine is carried out by our biobrick <a href="http://parts.igem.org/Part:BBa_K1205000">Carnitine Dehydrogenase</a>.  This protein catalyzes the conversion of L-carnitine into 3-Dehydrocarnitine, pushing it down an alternative metabolic pathway towaord the creation of the amino acid glycine.<br><br>
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The cells containing the biological parts are then suspended within calcium alginate and inserted into gelatin capsules in order to transport them to the intestinal system.
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Revision as of 03:16, 28 September 2013

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Project Overview and Abstract



Cardiovascular disease (CVD) has been the leading cause of death in the United States for over twenty years and is becoming a severe global health issue. CVD is highly associated with the buildup of plaque in arteries, a disease known as Atherosclerosis. Trimethylamine N-oxide (TMAO) is a known proatherogenic substance, and is abundant in carnivorous humans and those who consume energy drinks. It is the goal of the University of Illinois at Urbana Champaign (UIUC) iGEM Team to lower the amount of TMAO found in such individuals and therefore reduce the risk of atherosclerosis for those afflicted.TMAO is produced when the gut microbiota process the amino acid derivatives L-carnitine and choline. These metabolites are abundant in red meats and energy drinks, and are important bodily compounds; however, humans are intrinsically capable of producing the necessary amounts. When these substances are consumed, specific gut bacteria convert L-carnitine and choline into a harmful byproduct trimethylamine (TMA.) To protect itself, the liver oxidizes TMA into TMAO. We are creating a probiotic to outcompete the gut bacteria for L-carnitine and choline to effectively lower and ultimately remove the atherogenic activity caused by TMAO. Pseudomonas aeruginosa is a bacterium with novel adaptations that enable it to uptake L-carnitine as a sole source of carbon and nitrogen. These genes have been selected for and are being tested in various Escherichia coli.