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<h3> Project Description </h3>
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  <h3> An oxytocin diagnostic toolkit and<br>biotools for use in low-resource environments </h3>
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In 2015, over 300,000 women died during pregnancy and childbirth; 99% of these deaths occurred in developing countries. Postpartum hemorrhage (PPH), or severe bleeding after birth, is the leading cause of maternal mortality worldwide. Oxytocin is a naturally occurring hormone and a medication that is used to increase contractions in the uterus (i.e., induce labor). It has also proved effective in significantly reducing the risk of PPH. Oxytocin is now routinely used in industrialized countries, and is often given in small doses simply as a preventative measure in normal labors. However, oxytocin is not readily available in developing countries. Despite being on the World Health Organization’s List of Essential Medicines for developing countries and being relatively inexpensive (as of 2014, the wholesale cost of the medication is US$0.1–0.56 per dose), oxytocin requires storage at between 2 and 8 °C, which has led to a shortage of this critical drug in rural areas that lack reliable refrigeration, power, and infrastructure. <b>Quality issues with existing oxytocin inventories have also been identified as a significant issue in rural areas.</b></p>
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    Health clinics in resource-poor settings face significant challenges with quality and standardization of medications. Our project uses yeast to detect the presence of a specific medication, oxytocin – a naturally occurring hormone and medication that prevents postpartum hemorrhage during childbirth – the leading cause of maternal mortalities worldwide. Unrefrigerated oxytocin has a half-life of ~3 minutes, and only 8% of samples tested in a 2012 study in Ghana were kept at the appropriate temperature. Expired, low-quality, and unavailable medications are common occurrences throughout the developing world, but little is known about the impact on maternal outcomes due in part to the lack of low-cost diagnostic tests. Our interdisciplinary community lab has also built many of the tools we use in our lab every day emphasizing our commitment and motivation to continue working on creating robust low-cost biological tools and systems that can be deployed and used in economically underdeveloped areas.
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<p class="main"> Our first goal is to build an oxytocin detection system using a G-protein coupled receptor in yeast that will allow us to verify the presence of active oxytocin. If successful, we will then focus our efforts on synthesizing oxytocin in various forms to increase its availability in resource-poor areas.</p>
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<p class = "main"> Oxytocin is produced in the body by the OXT gene. It is synthesized as an inactive precursor peptide along with its carrier molecule neurophysin I. After several iterations of hydrolyzation via enzymes, the active oxytocin molecule is produced. In 2013 an iGEM team from Lethbridge Canada created a form of oxytocin still attached to its carrier molecule, neurophysin I, which prevents degradation until the carrier molecule is cleaved resulting in the activation of the oxytocin molecule. Our team plans to significantly build on this prior work by exploring several other approaches to improving the stability of oxytocin including producing a powdered form of the drug that can be activated using hydrolysis, adding trace metals to prevent oxidation, and using optogenetic techniques to activate oxytocin using light. In addition to these synthetic biology approaches, the diversity of our team’s skills will allow us to explore several mechanical and hardware solutions including simple, non-refrigerated single-injection systems; biological packaging solutions to prevent oxytocin’s degradation; and <b>testing systems to evaluate the quality and effectiveness of current oxytocin inventories.</b> The solutions we plan to explore will target practices ranging from manufacturing, transportation and storage, and distribution to drug administration protocols, drug quality monitoring and control, and improved documentation and inventory to support further research and quality care.The potential impact of any and all of these solutions will be to increase the availability of oxytocin for use in under-resourced maternity facilities. </p>
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<p class = "main">Successful microscopy  has confirmed the viability of EutS and EutC-eGFP in E.Coli, but the laser used to excite eGFP may also cause conformational change of azo-benzene. Instead Neptune, another light activated protein that is excited at a much longer wavelength, will be used to visualize the formation and destruction of EutS microcompartments. Future work will focus on the implementation of a multiconstruct system with EutS, EuC-Neptune, and a third construct that creates tRNA’s to integrate azo-benzene into the EutS at locations we expect to see significant steric hinderance. Instead Neptune, another light activated protein that is excited at a much longer wavelength, will be used to visualize the formation and destruction of EutS microcompartments. </p>
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<p class = "main">Future work will focus on the implementation of a multiconstruct system with EutS, EuC-Neptune, and a third construct that creates tRNA’s to integrate azo-benzene into the EutS at locations we expect to see significant steric hinderance.Instead Neptune, another light activated protein that is excited at a much longer wavelength, will be used to visualize the formation and destruction of EutS microcompartments. Future work will focus on the implementation of a multiconstruct system with EutS, EuC-Neptune, and a third construct that creates tRNA’s to integrate azo-benzene into the EutS at locations we expect to see significant steric hinderance. Future work will focus on the implementation of a multiconstruct system with EutS, EuC-Neptune, and a third construct that creates tRNA’s to integrate azo-benzene into the EutS at locations we expect to see significant steric hinderance.Future work will focus on the implementation of a multiconstruct system with EutS.  Future work will focus on the implementation of a multiconstruct system with EutS, EuC-Neptune, and a third construct that creates tRNA’s to integrate azo-benzene into the EutS at locations we expect to see significant steric hinderance. Successful microscopy  has confirmed the viability of EutS and EutC-eGFP in E.Coli, but the laser used to excite eGFP may also cause conformational change of azo-benzene. Instead Neptune, another light activated protein that is excited at a much longer wavelength, will be used to visualize the formation and destruction of EutS microcompartments. Future work will focus on the implementation of a multiconstruct system with EutS, EuC-Neptune, and a third construct that creates tRNA’s to integrate azo-benzene into the EutS at locations we expect to see significant steric hinderance. </p>
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<p class = "main">Successful microscopy has confirmed the viability of EutS and EutC-eGFP in E.Coli, but the laser used to excite eGFP may also cause conformational change of azo-benzene. Instead Neptune, another light activated protein that is excited at a much longer wavelength, will be used to visualize the formation and destruction of EutS microcompartments. Future work will focus on the implementation of a multiconstruct system with EutS, EuC-Neptune, and a third construct that creates tRNA’s to integrate azo-benzene into the EutS at locations we expect to see significant steric hinderance. Instead Neptune, another light activated protein that is excited at a much longer wavelength, will be used to visualize the formation and destruction of EutS microcompartments. Future work will focus on the implementation of a multiconstruct system with EutS, EuC-Neptune, and a third construct that creates tRNA’s to integrate azo-benzene into the EutS at locations we expect to see significant steric hinderance.Instead Neptune, another light activated protein that is excited at a much longer wavelength, will be used to visualize the formation and destruction of EutS microcompartments. Future work will focus on the implementation of a multiconstruct system with EutS, EuC-Neptune, and a third construct that creates tRNA’s to integrate azo-benzene into the EutS at locations we expect to see significant steric hinderance. Future work will focus on the implementation of a multiconstruct system with EutS, EuC-Neptune, and a third construct that creates tRNA’s to integrate azo-benzene into the EutS at locations we expect to see significant steric hinderance. Future work will focus on the implementation of a multiconstruct system with EutS, EuC-Neptune, and a third construct that creates tRNA’s to integrate azo-benzene into the EutS at locations we expect to see significant steric hinderance.</p>
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<p class = "main"> Successful microscopy  has confirmed the viability of EutS and EutC-eGFP in E.Coli, but the laser used to excite eGFP may also cause conformational change of azo-benzene. Instead Neptune, another light activated protein that is excited at a much longer wavelength, will be used to visualize the formation and destruction of EutS microcompartments. Future work will focus on the implementation of a multiconstruct system with EutS, EuC-Neptune, and a third construct that creates tRNA’s to integrate azo-benzene into the EutS at locations we expect to see significant steric hinderance. </p>
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<p>While you may not win Best Wiki with this styling, your team is still eligible for all other awards. This default wiki meets the requirements, it improves navigability and ease of use for visitors, and you should not feel it is necessary to style beyond what has been provided.</p>
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Team:Denver_Biolabs

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An oxytocin diagnostic toolkit and
biotools for use in low-resource environments


Health clinics in resource-poor settings face significant challenges with quality and standardization of medications. Our project uses yeast to detect the presence of a specific medication, oxytocin – a naturally occurring hormone and medication that prevents postpartum hemorrhage during childbirth – the leading cause of maternal mortalities worldwide. Unrefrigerated oxytocin has a half-life of ~3 minutes, and only 8% of samples tested in a 2012 study in Ghana were kept at the appropriate temperature. Expired, low-quality, and unavailable medications are common occurrences throughout the developing world, but little is known about the impact on maternal outcomes due in part to the lack of low-cost diagnostic tests. Our interdisciplinary community lab has also built many of the tools we use in our lab every day emphasizing our commitment and motivation to continue working on creating robust low-cost biological tools and systems that can be deployed and used in economically underdeveloped areas.

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