http://2014.igem.org/wiki/index.php?title=Special:Contributions&feed=atom&limit=20&target=Waqar&year=&month=2014.igem.org - User contributions [en]2024-03-29T11:13:13ZFrom 2014.igem.orgMediaWiki 1.16.5http://2014.igem.org/Talk:Team:Warwick/TeamTalk:Team:Warwick/Team2015-07-22T17:15:51Z<p>Waqar: moved Talk:Team:Warwick/Team to Talk:Team:Warwick/Team2</p>
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Welcome to the official Wiki of the first University of Warwick 2014 iGEM team. Our team consists of members from different disciplines all having a common interest in the area of Synthetic biology coming together to compete, collaborate and contribute!<br />
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Small interfering RNAs (siRNAs) represent a diverse family of biological regulators that are able to bind specifically to mRNA and prevent translation. siRNAs have been used in reverse genetics to understand the function of genes in gene knock-out studies. It has become apparent from a clinical viewpoint that siRNAs represent one type of therapeutic against diseases which have abberant gene expression profilessuch as alzheimers and cancer. <br />
siRNAs work through a conserved evolutionariy mechanism, specific to eukaryotes that utilizes the enzyme RNAse type 3 enzyme Dicer, that is able to dice a siRNA <br />
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Our project involves the production of a self-replicating RNA system, utilizing the well characterized Hepatitis C virus subtype 1b RNA dependent RNA polymerase (RdRp). By using a number of different biological components, We wish to develop a system whereby small interfering RNAs (siRNAs) are produced intermittently; without having the need to systematically introduce siRNAs through injectable delievery into patients. As we circumvent the biological flow of information at the level of mRNA, our system overcomes the limitation of gene therapeutic methods which utilize vectors that routinely integrate into the host genome and can downregulate, or activate genes <br />
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</table></div>Waqarhttp://2014.igem.org/Team:Warwick/TeamTeam:Warwick/Team2015-07-22T17:15:51Z<p>Waqar: moved Team:Warwick/Team to Team:Warwick/Team2</p>
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<div>#REDIRECT [[Team:Warwick/Team2]]</div>Waqarhttp://2014.igem.org/Team:Warwick/Team2Team:Warwick/Team22015-07-22T17:15:51Z<p>Waqar: moved Team:Warwick/Team to Team:Warwick/Team2</p>
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<li> <a href = "/Team:Warwick"> HOME </a> </li><br />
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<h1>Students</h1><br />
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<td><img src="https://static.igem.org/mediawiki/2014/4/4f/Warwick_Hassan_pic.jpg" alt="photo of Hassan" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Hassan Chaudhry</b></font></ins> <br>Hassan is a Mathematician at Warwick and found himself leader of the team and inadvertently our resident travel agent. He also took a firm hand in organising and keeping on top of the team while developing models for many of the parts in the meantime. Unfortunately, developing an allergic reaction to a tree he had come "very close to touching" outside the lab, he refused to dine al fresco with the rest of the team on the (rare) hot summer days. </td><br />
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<td><img src="https://static.igem.org/mediawiki/2014/1/19/Warwick_Leo_pic.jpg" alt="photo of Leo" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Leo Vong</b></font></ins> <br>Leo is a 2nd year student studying Biochemistry at Warwick, hailing from all over the midlands. He was key to sponsorship, obtaining free gloves, laboratory reagents and other samples needed for our work in the laboratory.</td><br />
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<td><img src="https://static.igem.org/mediawiki/2014/4/44/Warwick_Chris_pic.jpg" alt="photo of Chris" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Chris Davis</b></font></ins> <br>Chris is studying Physics at Warwick and was our honorary computer scientist taking the wiki by storm. He was also a major part in our data analysis and was driven almost insane by biologists and their "continuous lack of enough repeats and far too many abbreviations".</td><br />
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<td><img src="https://static.igem.org/mediawiki/2014/6/69/Warwick_Iva_pic.jpg" alt="photo of Iva" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Iva Burova</b></font></ins> <br>Iva has ventured furthest from home, coming from Bulgaria and is studying Engineering at Warwick, looking to specialise into biomedical engineering post uni. She took a shine to the lab work, deeming everything "so adorable", and kept a meticulous lab book where you could find anything and everything experiment related. She was infinitely helpful, coming in at weekends and staying late every evening in order to complete the tasks at hand and studying for her exams alongside.</td><br />
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<td><img src="https://static.igem.org/mediawiki/2014/d/df/Warwick_Dan_pic.jpg" alt="photo of Dan" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Dan Goss</b></font></ins> <br>After briefly lapsing his strong vegan beliefs and accepting the use of fetal bovine serum and calf intestinal alkaline phosphatase in the lab, he took charge of the measurement study and put his controversial views to good use at the forefront of our human practice ventures. He spurned interesting and heated debates about the project and its applications as well as its environmental impacts.</td><br />
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<td><img src="https://static.igem.org/mediawiki/2014/4/45/Warwick_Chelsey_pic.jpg" alt="photo of Chelsey" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Chelsey Tye</b></font></ins> <br>Chelsey is currently studying in Chemistry following a 3 year undergraduate course in Chemical Biology at Warwick. She helped Dan in the measurement study and human practices area.</td><br />
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<td><img src="https://static.igem.org/mediawiki/2014/9/98/Warwick_Carrie_pic.jpg" alt="photo of Carrie" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Caroline de Cock</b></font></ins> <br>Carrie studies biomedical science at Warwick and played a major role in the experimental side of the project. She was particularly crucial to the testing in human cells which she particularly enjoyed and successfully tested the IRESs and the aptazyme following some set backs in transfection. Despite her tendency to fall asleep unannounced, she played a key role in the experimental planning and aquiring of results.</td><br />
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<td><img src="https://static.igem.org/mediawiki/2014/2/2e/Warwick_Becky.jpg" alt="photo of Becky" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Becky Seeley</b></font></ins> <br>Becky studies biomedical sciences at Warwick university and is in her final year. Becky took on a major role in the experimetal work.</td><br />
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<td><img src="https://static.igem.org/mediawiki/2014/7/75/Warwick_Ben_pic.jpg" alt="photo of Ben" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Ben Livingstone</b></font></ins> <br>Ben was king of the modelling, taking major steps forward in the development of both stochastic and deterministic models, as well as creating a programme to speed up the analysis of plates measured in the tecan, instructions for and details of which can be found in the modelling section of our wiki. </td><br />
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<h1>Supervisors/Advisors</h1> <br />
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<td><img src="https://static.igem.org/mediawiki/2014/3/3c/Warwick_Alfonso_pic.jpg" alt="photo of Alfonso" height="200" width="150" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Alfonso Jaramillo</b></font></ins> <br>Alfonso was our PI. With a PhD in theoretical Physics he moved over to Synthetic Biology, shortly after which he involved himself in iGEM in 2006 and has never looked back. His group is currently engineering a synthetic phage, developing directed evolution technologies and engineering novel RNA devices.</td><br />
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<td><img src="https://static.igem.org/mediawiki/2014/3/33/Warwick_Sian_pic.jpg" alt="photo of Sian" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Sian Davies</b></font></ins> <br>Sian was our secondary supervisor with a PhD in plant biological clocks. She aided in experimental design and kept us on track, giving us our initial safety briefing and crash course in cloning.</td><br />
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<td><b><ins><font size="4">William Rostain</b></font></ins> <br> Will was an advisor. He is a current PhD student working in the Jaramillo laboratory developing RNA switches and synthetic phages for future antibiotic therapy. He earned his BSc in Edinburgh in Biology and has been involved in three iGEM teams as both a student and advisor, earning gold with additional prizes in each one, in the undergraduate and postgraduate category.<br />
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<td><img src="https://static.igem.org/mediawiki/2014/4/4f/Warwick_Hassan_pic.jpg" alt="photo of Hassan" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Hassan Chaudhry</b></font></ins> <br>Hassan is a Mathematician at Warwick and found himself leader of the team and inadvertently our resident travel agent. He also took a firm hand in organising and keeping on top of the team while developing models for many of the parts in the meantime. Unfortunately, developing an allergic reaction to a tree he had come "very close to touching" outside the lab, he refused to dine al fresco with the rest of the team on the (rare) hot summer days. </td><br />
</tr><br />
<br />
<br />
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<td><img src="https://static.igem.org/mediawiki/2014/1/19/Warwick_Leo_pic.jpg" alt="photo of Leo" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Leo Vong</b></font></ins> <br>Leo is a 2nd year student studying Biochemistry at Warwick, hailing from all over the midlands. He was key to sponsorship, obtaining free gloves, laboratory reagents and other samples needed for our work in the laboratory.</td><br />
</tr><br />
<br />
<tr><br />
<td><img src="https://static.igem.org/mediawiki/2014/4/44/Warwick_Chris_pic.jpg" alt="photo of Chris" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Chris Davis</b></font></ins> <br>Chris is studying Physics at Warwick and was our honorary computer scientist taking the wiki by storm. He was also a major part in our data analysis and was driven almost insane by biologists and their "continuous lack of enough repeats and far too many abbreviations".</td><br />
</tr><br />
<br />
<tr><br />
<td><img src="https://static.igem.org/mediawiki/2014/6/69/Warwick_Iva_pic.jpg" alt="photo of Iva" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Iva Burova</b></font></ins> <br>Iva has ventured furthest from home, coming from Bulgaria and is studying Engineering at Warwick, looking to specialise into biomedical engineering post uni. She took a shine to the lab work, deeming everything "so adorable", and kept a meticulous lab book where you could find anything and everything experiment related. She was infinitely helpful, coming in at weekends and staying late every evening in order to complete the tasks at hand and studying for her exams alongside.</td><br />
</tr><br />
<br />
<tr><br />
<td><img src="https://static.igem.org/mediawiki/2014/d/df/Warwick_Dan_pic.jpg" alt="photo of Dan" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Dan Goss</b></font></ins> <br>After briefly lapsing his strong vegan beliefs and accepting the use of fetal bovine serum and calf intestinal alkaline phosphatase in the lab, he took charge of the measurement study and put his controversial views to good use at the forefront of our human practice ventures. He spurned interesting and heated debates about the project and its applications as well as its environmental impacts.</td><br />
</tr><br />
<br />
<tr><br />
<td><img src="https://static.igem.org/mediawiki/2014/4/45/Warwick_Chelsey_pic.jpg" alt="photo of Chelsey" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Chelsey Tye</b></font></ins> <br>Chelsey is currently studying in Chemistry following a 3 year undergraduate course in Chemical Biology at Warwick. She helped Dan in the measurement study and human practices area.</td><br />
</tr><br />
<br />
<tr><br />
<td><img src="https://static.igem.org/mediawiki/2014/9/98/Warwick_Carrie_pic.jpg" alt="photo of Carrie" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Caroline de Cock</b></font></ins> <br>Carrie studies biomedical science at Warwick and played a major role in the experimental side of the project. She was particularly crucial to the testing in human cells which she particularly enjoyed and successfully tested the IRESs and the aptazyme following some set backs in transfection. Despite her tendency to fall asleep unannounced, she played a key role in the experimental planning and aquiring of results.</td><br />
</tr><br />
<tr><br />
<td><img src="https://static.igem.org/mediawiki/2014/2/2e/Warwick_Becky.jpg" alt="photo of Becky" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Becky Seeley</b></font></ins> <br>Becky studies biomedical sciences at Warwick university and is in her final year. Becky took on a major role in the experimetal work.</td><br />
</tr><br />
<br />
<tr><br />
<td><img src="https://static.igem.org/mediawiki/2014/7/75/Warwick_Ben_pic.jpg" alt="photo of Ben" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Ben Livingstone</b></font></ins> <br>Ben was king of the modelling, taking major steps forward in the development of both stochastic and deterministic models, as well as creating a programme to speed up the analysis of plates measured in the tecan, instructions for and details of which can be found in the modelling section of our wiki. </td><br />
</tr><br />
</table><br />
<h1>Supervisors/Advisors</h1> <br />
<table align="left" style="float: left;<br />
clear: left;"><br />
<tr><br />
<br />
<tr><br />
<td><img src="https://static.igem.org/mediawiki/2014/3/3c/Warwick_Alfonso_pic.jpg" alt="photo of Alfonso" height="200" width="150" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Alfonso Jaramillo</b></font></ins> <br>Alfonso was our PI. With a PhD in theoretical Physics he moved over to Synthetic Biology, shortly after which he involved himself in iGEM in 2006 and has never looked back. His group is currently engineering a synthetic phage, developing directed evolution technologies and engineering novel RNA devices.</td><br />
</tr><br />
<br />
<tr><br />
<td><img src="https://static.igem.org/mediawiki/2014/3/33/Warwick_Sian_pic.jpg" alt="photo of Sian" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Sian Davies</b></font></ins> <br>Sian was our secondary supervisor with a PhD in plant biological clocks. She aided in experimental design and kept us on track, giving us our initial safety briefing and crash course in cloning.</td><br />
</tr><br />
<br />
<tr><br />
<td><img src='https://static.igem.org/mediawiki/2013/2/21/Steinbock.png' alt='William' height='200px' width="200" style="margin: 0px 250px opx 0px"></td><br />
<td><b><ins><font size="4">William Rostain</b></font></ins> <br> Will was an advisor. He is a current PhD student working in the Jaramillo laboratory developing RNA switches and synthetic phages for future antibiotic therapy. He earned his BSc in Edinburgh in Biology and has been involved in three iGEM teams as both a student and advisor, earning gold with additional prizes in each one, in the undergraduate and postgraduate category.<br />
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<h1>Students</h1><br />
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<td><img src="https://static.igem.org/mediawiki/2014/4/4f/Warwick_Hassan_pic.jpg" alt="photo of Hassan" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Hassan Chaudhry</b></font></ins> <br>Hassan is a Mathematician at Warwick and found himself leader of the team and inadvertently our resident travel agent. He also took a firm hand in organising and keeping on top of the team while developing models for many of the parts in the meantime. Unfortunately, developing an allergic reaction to a tree he had come "very close to touching" outside the lab, he refused to dine al fresco with the rest of the team on the (rare) hot summer days. </td><br />
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<td><img src="h" alt="photo of Waq" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Waqar Yousaf</b></font></ins> <br>Waq is a student at Warwick following an Undergraduate Masters degree. He is studying under supervisors Miriam Gifford and Vardis Ntoukakis, investigating the hidden mechanisms of innate immunity. He was mainly involved in the experimental side of the project, the interlab study and human practices. Also provided entertainment, wearing inappropriate clothes in the harshly air-conditioned computer lab and his questionable drawing skills.</td><br />
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<td><img src="https://static.igem.org/mediawiki/2014/1/19/Warwick_Leo_pic.jpg" alt="photo of Leo" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Leo Vong</b></font></ins> <br>Leo is a 2nd year student studying Biochemistry at Warwick, hailing from all over the midlands. He was key to sponsorship, obtaining free gloves, laboratory reagents and other samples needed for our work in the laboratory.</td><br />
</tr><br />
<br />
<tr><br />
<td><img src="https://static.igem.org/mediawiki/2014/4/44/Warwick_Chris_pic.jpg" alt="photo of Chris" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Chris Davis</b></font></ins> <br>Chris is studying Physics at Warwick and was our honorary computer scientist taking the wiki by storm. He was also a major part in our data analysis and was driven almost insane by biologists and their "continuous lack of enough repeats and far too many abbreviations".</td><br />
</tr><br />
<br />
<tr><br />
<td><img src="https://static.igem.org/mediawiki/2014/6/69/Warwick_Iva_pic.jpg" alt="photo of Iva" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Iva Burova</b></font></ins> <br>Iva has ventured furthest from home, coming from Bulgaria and is studying Engineering at Warwick, looking to specialise into biomedical engineering post uni. She took a shine to the lab work, deeming everything "so adorable", and kept a meticulous lab book where you could find anything and everything experiment related. She was infinitely helpful, coming in at weekends and staying late every evening in order to complete the tasks at hand and studying for her exams alongside.</td><br />
</tr><br />
<br />
<tr><br />
<td><img src="https://static.igem.org/mediawiki/2014/d/df/Warwick_Dan_pic.jpg" alt="photo of Dan" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Dan Goss</b></font></ins> <br>After briefly lapsing his strong vegan beliefs and accepting the use of fetal bovine serum and calf intestinal alkaline phosphatase in the lab, he took charge of the measurement study and put his controversial views to good use at the forefront of our human practice ventures. He spurned interesting and heated debates about the project and its applications as well as its environmental impacts.</td><br />
</tr><br />
<br />
<tr><br />
<td><img src="https://static.igem.org/mediawiki/2014/4/45/Warwick_Chelsey_pic.jpg" alt="photo of Chelsey" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Chelsey Tye</b></font></ins> <br>Chelsey is currently studying in Chemistry following a 3 year undergraduate course in Chemical Biology at Warwick. She helped Dan in the measurement study and human practices area.</td><br />
</tr><br />
<br />
<tr><br />
<td><img src="https://static.igem.org/mediawiki/2014/9/98/Warwick_Carrie_pic.jpg" alt="photo of Carrie" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Caroline de Cock</b></font></ins> <br>Carrie studies biomedical science at Warwick and played a major role in the experimental side of the project. She was particularly crucial to the testing in human cells which she particularly enjoyed and successfully tested the IRESs and the aptazyme following some set backs in transfection. Despite her tendency to fall asleep unannounced, she played a key role in the experimental planning and aquiring of results.</td><br />
</tr><br />
<tr><br />
<td><img src="https://static.igem.org/mediawiki/2014/2/2e/Warwick_Becky.jpg" alt="photo of Becky" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Becky Seeley</b></font></ins> <br>Becky studies biomedical sciences at Warwick university and is in her final year. Becky took on a major role in the experimetal work.</td><br />
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<br />
<tr><br />
<td><img src="https://static.igem.org/mediawiki/2014/7/75/Warwick_Ben_pic.jpg" alt="photo of Ben" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Ben Livingstone</b></font></ins> <br>Ben was king of the modelling, taking major steps forward in the development of both stochastic and deterministic models, as well as creating a programme to speed up the analysis of plates measured in the tecan, instructions for and details of which can be found in the modelling section of our wiki. </td><br />
</tr><br />
</table><br />
<h1>Supervisors/Advisors</h1> <br />
<table align="left" style="float: left;<br />
clear: left;"><br />
<tr><br />
<br />
<tr><br />
<td><img src="https://static.igem.org/mediawiki/2014/3/3c/Warwick_Alfonso_pic.jpg" alt="photo of Alfonso" height="200" width="150" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Alfonso Jaramillo</b></font></ins> <br>Alfonso was our PI. With a PhD in theoretical Physics he moved over to Synthetic Biology, shortly after which he involved himself in iGEM in 2006 and has never looked back. His group is currently engineering a synthetic phage, developing directed evolution technologies and engineering novel RNA devices.</td><br />
</tr><br />
<br />
<tr><br />
<td><img src="https://static.igem.org/mediawiki/2014/3/33/Warwick_Sian_pic.jpg" alt="photo of Sian" height="200" width="200" style="margin: 0px 250px opx 0px"></td><td><b><ins><font size="4">Sian Davies</b></font></ins> <br>Sian was our secondary supervisor with a PhD in plant biological clocks. She aided in experimental design and kept us on track, giving us our initial safety briefing and crash course in cloning.</td><br />
</tr><br />
<br />
<tr><br />
<td><img src='https://static.igem.org/mediawiki/2013/2/21/Steinbock.png' alt='William' height='200px' width="200" style="margin: 0px 250px opx 0px"></td><br />
<td><b><ins><font size="4">William Rostain</b></font></ins> <br> Will was an advisor. He is a current PhD student working in the Jaramillo laboratory developing RNA switches and synthetic phages for future antibiotic therapy. He earned his BSc in Edinburgh in Biology and has been involved in three iGEM teams as both a student and advisor, earning gold with additional prizes in each one, in the undergraduate and postgraduate category.<br />
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<br> <p> Welcome to the biological world in which we've spent an entire summer creating, working on and perfecting. We're introducing RNA to synthetic biology in a big way, by directly contributing a number of key parts to iGEM. We've taken a risk, we've been told our project is unrealistic and should be scraped, that a group of undergraduates are crazy for even thinking about doing something so complicated. Even at times, we ourselves doubted - there's been the good times and the bad. Spurred on by a desire to make a difference to synthetic biology and the world in which we live in, we pressed forward - a new team to iGEM, not seasoned veterans. We take chances and risks to make a difference - whether success comes our way or failure, we embrace the moment, cherishing it. We hope the synthetic biology community will appreciate our efforts, as RNA increases in use and popularity. DNA is best served as a template for information storage. RNA is multi-functional, catalytic and dynamic, welcome to our world - the RNA world.<br> <br />
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- Warwick iGEM Team 2014 <br />
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<br> <p> Welcome to the biological world in which we've spent an entire summer creating, working on and perfecting. We're introducing RNA to synthetic biology in a big way, by directly contributing a number of key parts to iGEM. We've taken a risk, we've been told our project is unrealistic and should be scraped, that a group of undergraduates are crazy for even thinking about doing something so complicated. Even at times, we ourselves doubted - there's been the good times and the bad. Spurred on by a desire to make a difference to synthetic biology and the world in which we live in, we pressed forward - a new team to iGEM, not seasoned veterans. We take chances and risks to make a difference - whether success comes our way or failure, we embrace the moment, cherishing it. We hope the synthetic biology community will appreciate our efforts, as RNA increases in use and popularity. DNA is best served as a template for information storage. RNA is multi-functional, catalytic and dynamic, welcome to our world - the RNA world. If you're still reading at this point<br> <br />
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<br> <p> Welcome to the biological world in which we've spent an entire summer creating, working on and perfecting. We're introducing RNA to synthetic biology in a big way, by directly contributing a number of key parts to iGEM. We've taken a risk, we've been told our project is unrealistic and should be scraped, that a group of undergraduates are crazy for even thinking about doing something so complicated. Even at times, we ourselves doubted - there's been the good times and the bad. Spurred on by a desire to make a difference to synthetic biology and the world in which we live in, we pressed forward - a new team to iGEM, not seasoned veterans. We take chances and risks to make a difference - whether success comes our way or failure, we embrace the moment, cherishing it. We hope the synthetic biology community will appreciate our efforts, as RNA increases in use and popularity. DNA is best served as a template for information storage. RNA is multi-functional, catalytic and dynamic, welcome to our world - the RNA world. If you're still reading at this point<br> <br />
<br />
Welcome<br />
Croeso<br />
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Добре дошло<br />
Laipni lūdzam<br />
<br />
- Warwick iGEM 2014 <br />
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<li style="list-style-type: none;"><a href="#Motivation"><span class="tocnumber">1. </span><span class="toctext">Motivation</span></a></li><br />
<li style="list-style-type: none;"><a href="#what_is_a_replicon?"><span class="tocnumber">2. </span><span class="toctext">What is a replicon?</span></a></li><br />
<li style="list-style-type: none;"><a href="#What_are_the_advantages_of_this_over_conventional_gene_therapy?"><span class="tocnumber">3. </span><span class="toctext">What are the advantages of this over conventional gene therapy?</span></a></li><br />
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<p id="Motivation"><b><ins><font size="4">MOTIVATION</b></font></ins> <br><br />
After much deliberation over many project ideas, either expanding on previous projects or alternative substrates for existing parts, we decided we wanted to open up a whole new world of opportunities for Synthetic Biology. Developing the basics for a new realm in the field of RNA. Using a combination of experiments in Escherichia coli (E.coli) and human cells, both HeLa and Huh7.5 we attempted to turn on the lights to RNA world experimentation.<br><img src="https://static.igem.org/mediawiki/parts/b/bc/RNA_strnad.PNG" width="900px"/></p><br />
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<p>Until now RNA has been used sparingly in iGEM with teams tiptoeing around the idea with little advancement. We wanted to set the groundwork for future teams to have the option of classical Synthetic Biology i.e. DNA projects or new projects in RNA world. We feel this is a hugely exciting new area for research to begin as we were initially struggling with originality of our project due to the exponential increase in iGEM teams and projects done previously and underway. RNA is a fascinating alternative for projects. We decided the fundamentals were: an RNA repressor, promoter, ribosome binding site (RBS), kill switch, a replication system and demonstrating the potentials with our own part. These were combined into a self-replicating RNA strand or “Replicon”. These demonstrate a use of all the elements together however the potential permutations and adaptations of these parts are endless.</p> <br><br />
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<br />
<p>Deciding on how to utilise our system we had a huge number of potential experiments but decided we would focus our efforts on current and important world health problems. These were narrowed down to; type II diabetes mellitus and, on further research into current events, Ebola. Type II diabetes is a pandemic of epic proportions, on the rise in all corners of the globe of all race and age, in part due to the increase trend in obesity and glucose consumption.</p> <br><br />
<br />
<p></p><br><p><font size="5"><b>America</b></font> <br> <br> <img src="http://img.medscape.com/article/738/271/738271-fig1.jpg" width="370" height="353" /></p><br />
<p> <br> </p> <br> <br><br />
<br />
<p><br><p><font size="5"><b>England</b></font> <br> <br> <img src="http://www.bbc.co.uk/schools/gcsebitesize/science/images/edex_bio_obesity.jpg" width="400" height="353"/></p><br />
<br> <br><br />
<br />
<p></p> <br> <p><font size="5"><b>Comparison by Race</b></font> <br> <br> <img src="http://www.cdc.gov/diabetes/statistics/prev/national/fAgeStandardizedPrevalenceByRaceEthnicitySex.gif"/></p><br />
<p></p> <br> <br />
<br> <br><br />
<p></p> <br> <p><font size="5"><b>Worldwide</b></font> <br> <br> <img src="https://www.sanger.ac.uk/research/projects/metabolicdisease/gfx/metabolicdisease_graph_316x302.png"/></p><br />
<br />
<p>These graphs clearly demonstrate the growing problem posed by diabetes. People of all races, in all corners of the globe are requiring constant monitoring and treatment for this disorder. The treatment require frequent hospital or doctor's appointments and daily injections and/or tablets to relieve the symptoms and damaging effects of diabetes. This costs the healthcare systems in many countries billions of dollars already and could double if those currently living unaware of their condition were to be diagnosed. Almost every individual in America and Europe will have a friend or family member affected with this disease and causes heartache to thousands more following death and pain of sufferers.</p><br />
<p> <br> <br> </p><br />
<p><center><img src="http://i.dailymail.co.uk/i/pix/2014/05/05/article-2620987-1D97B22800000578-267_634x241.jpg" width="75%"/></center></p><br />
<p> <br> <br> </p><br />
<br />
<p>Treatments for Type II diabetes range from the simple; lose weight and consume less sugar to the expensive; gene therapy and dipeptidylpeptidase IV (DPP-IV) inhibitors costing $900 for 90 tablets, and the painful; amputations.<br />
DPP-IV, due to its cellular, genomic origin seemed like an appropriate target to tackle using our system. DPP-IV inhibitors are administered in stage two of treatment directly after lifestyle changes and are used to slow the degradation of incretins such as glucose like peptides which is accelerated by DPP-IV. Incretins act to increase the duration of insulin release and hence increasing the probability of response from the insulin resistant cells. In this way the insulin resistance can in part be masked.</p><p> </p><p></p><p></p><br />
<br />
<p>Gene therapy has been long sought after in biology and has already been implemented as a treatment for many disorders, such as functional CFTR gene therapy in cystic fibrosis sufferers. Its applications are extremely wide ranging, as by manipulating the genome a cell, you can in theory make it carry out the desired function or restore functionality where before there was disfunction. The key difference in our project is that gene therapy focuses on modifying the genome of cells while we are attempting to produce the same effect rather than individual cells on their own. There are many problems with current gene therapy, including it being dangerous and being extremely difficult to perform, is the possibility of modifying the DNA of cells in ways that can't be predicted and causing further issues by altering a necessary gene. Our project is to try and solve some of these problems by using a self replicating RNA strand we termed a 'replicon'. <br />
</p><br />
<p> <br> <br> </p><br />
<p id="what_is_a_replicon?"><b><ins><font size="4">What is a replicon?</b></font></ins> <br> A replicon is RNA that acts to replicate itself on its own using only the ribozymes of the cell. RNA usually degrades very quickly in cells, but a replicon should last permanently, because it should replicate faster than it can be degraded. Several viruses use replicons as their method of manipulating cells. Our idea is to take parts from the genome of hepatitis C (HCV) and modify it so that instead of doing damage to the body, it 'silences' harmful genes. To do this, we want to add an siRNA sequence to a replicon sequence. siRNA (small interfering RNA) is RNA that contains part of a complimentary nucleotide sequence to a particular RNA sequence to which it associates forming a double stranded RNA fragment. Double stranded RNA is not endogenous to the cell and hence is recognised as foreign by Dicer and RISC, in the process detailed on <a href="https://2014.igem.org/Team:Warwick/Project/Howitworks">How it works</a>. The double stranded RNA is destroyed and RISC retains a form of memory for this sequence and will digest it spontaneously in subsequent exposures. We exploited this protection system to target our unwanted mRNA. <br />
</p> <br />
<br />
p></p> <br> <br><br />
<p id="RNA to Synthetic Biology"><b><ins><font size="4">RNA: Meet iGEM</b></font></ins> <br> </p><br />
<br />
<p> A self-replicating RNA system to produce an siRNA to target mRNA which would otherwise give rise to a deregulated protein is just one of the many applications of our system. We purposely as a team created a set of core parts and promoters, essentially creating a tool kit which allows any future iGEM team or researcher to take and use in their own system. This plug and play modularity is at the heart and soul of our motivation to give something to the synthetic biology community. We have the RNA dependent RNA polymerase, which propagates RNA templates. We have the aptazyme kill switch, which ensures regulation of our system or any system, the promoters, the terminators, the testing modules - you name it, we've most likely tested it. </p> <br />
<br />
<br />
<p></p> <br> <br><br />
<p id="What_are_the_advantages_of_this_over_conventional_gene_therapy?"><b><ins><font size="4">What are the advantages of this over conventional gene therapy?</b></font></ins> <br> Nowhere in this process is the actual DNA of the cell modified, so this removes the danger of DNA of the cell being modified in a way that is unwanted. This of course, prevents the problem of insertional mutagenesis with viral vectors that routinely integrate into the genome. <br />
<br />
This also improves upon conventional gene silencing, which involves siRNA only, as the replicon represents a permanent source of siRNA, greatly increasing the efficiency of the gene silencing. Our proposed method of delivery is to use a viral vector, technology which does exist but currently is limited in respect to specificity to particular cell types, avoiding recognition by the immune response and efficiency of uptake of the viral vector. In the future, we hope that someone may stumble across our idea and build upon it, so that the full potential of our system can be realized. </p><br />
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<br> <p> Welcome to the biological world in which we've spent an entire summer creating, working on and perfecting. We're introducing RNA to synthetic biology in a big way, by directly contributing a number of key parts to iGEM. We've taken a risk, we've been told our project is unrealistic and should be scraped, that a group of undergraduates are crazy for even thinking about doing something so complicated. Even at times, we ourselves doubted - there's been the good times and the bad. Spurred on by a desire to make a difference to synthetic biology and the world in which we live in, we pressed forward - a new team to iGEM, not seasoned veterans. We take chances and risks to make a difference - whether success comes our way or failure, we embrace the moment, cherishing it. If you're still reading at this point<br> <br />
<br />
Welcome<br />
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- Warwick iGEM 2014 <br />
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<p><font size="19"><b>~~~~~~~~~WELCOME TO RNA WORLD~~~~~~~~~~</b></font></p> <br> <br><br />
<br />
<br> <p> Welcome to the biological world in which we've spent an entire summer creating, working on and perfecting. We're introducing RNA to synthetic biology in a big way, by directly contributing a number of key parts to iGEM. We've taken a risk, we've been told our project is unrealistic and should be scraped, that a group of undergraduates are crazy for even thinking about doing something so complicated. Even at times, we ourselves doubted - there's been the good times and the bad. Spurred on by a desire to make a difference to synthetic biology and the world in which we live in, we pressed forward - a new team to iGEM, not seasoned veterans. We take chances and risks to make a difference - whether success comes our way or failure, we embrace the moment, cherishing it. If you're still reading at this point<br> <br />
<br />
Welcome<br />
Croeso<br />
歡迎<br />
خوش آمدید<br />
Добре дошло<br />
Laipni lūdzam<br />
<br />
- Warwick iGEM 2014 <br />
<br />
<br />
<p></p> <br><br />
<p></p> <br><br />
<p><center><a href="/Team:Warwick/Project/Motivation"><img src="https://static.igem.org/mediawiki/parts/d/d4/RNA_world.PNG" height="65%" width="65%"/></a></center></p><br />
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<p><font size="19"><b>~~~~~~~~~WELCOME TO RNA WORLD~~~~~~~~~~</b></font></p> <br> <br><br />
<br />
<br> <p> Welcome to the biological world in which we've spent an entire summer creating, working on and perfecting. We're introducing RNA to synthetic biology in a big way, by directly contributing a number of key parts to iGEM. We've taken a risk, we've been told our project is unrealistic and should be scraped, that a group of undergraduates are crazy for even thinking about doing something so complicated. Even at times, we ourselves doubted - there's been the good times and the bad. Spurred on by a desire to make a difference to synthetic biology and the world in which we live in, we pressed forward - a new team to iGEM, not seasoned veterans. We take chances and risks to make a difference - whether success comes our way or failure, we embrace the moment. If you're still reading at this point - Welcome to our world. <br> <br />
<br />
- Warwick iGEM 2014 <br />
<br />
<br />
<p></p> <br><br />
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<p><font size="19"><b>~~~~~~~~~WELCOME TO RNA WORLD~~~~~~~~~~</b></font></p> <br> <br><br />
<br />
<p> Welcome to the biological world in which we've spent an entire summer creating, working on and perfecting. We're introducing RNA to synthetic biology in a big way, by directly contributing a number of key parts to iGEM. We've taken a risk, we've been told our project is unrealistic and should be scraped, that a group of undergraduates are crazy for even thinking about doing something so complicated. Even at times, we ourselves doubted - there's been the good times and the bad. Spurred on by a desire to make a difference to synthetic biology and the world in which we live in, we pressed forward - a new team to iGEM, not seasoned veterans. We take chances and risks to make a difference - whether success comes our way or failure, we embrace the moment. If you're still reading at this point - Welcome to our world. <br />
<br />
- Warwick iGEM 2014 <br />
<br />
<br />
<p></p> <br><br />
<p></p> <br><br />
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<li style="list-style-type: none;"><a href="#what_is_a_replicon?"><span class="tocnumber">2. </span><span class="toctext">What is a replicon?</span></a></li><br />
<li style="list-style-type: none;"><a href="#What_are_the_advantages_of_this_over_conventional_gene_therapy?"><span class="tocnumber">3. </span><span class="toctext">What are the advantages of this over conventional gene therapy?</span></a></li><br />
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<p id="Motivation"><b><ins><font size="4">MOTIVATION</b></font></ins> <br><br />
After much deliberation over many project ideas, either expanding on previous projects or alternative substrates for existing parts, we decided we wanted to open up a whole new world of opportunities for Synthetic Biology. Developing the basics for a new realm in the field of RNA. Using a combination of experiments in Escherichia coli (E.coli) and human cells, both HeLa and Huh7.5 we attempted to turn on the lights to RNA world experimentation.<br><img src="https://static.igem.org/mediawiki/parts/b/bc/RNA_strnad.PNG" width="900px"/></p><br />
<br />
<p>Until now RNA has been used sparingly in iGEM with teams tiptoeing around the idea with little advancement. We wanted to set the groundwork for future teams to have the option of classical Synthetic Biology i.e. DNA projects or new projects in RNA world. We feel this is a hugely exciting new area for research to begin as we were initially struggling with originality of our project due to the exponential increase in iGEM teams and projects done previously and underway. RNA is a fascinating alternative for projects. We decided the fundamentals were: an RNA repressor, promoter, ribosome binding site (RBS), kill switch, a replication system and demonstrating the potentials with our own part. These were combined into a self-replicating RNA strand or “Replicon”. These demonstrate a use of all the elements together however the potential permutations and adaptations of these parts are endless.</p> <br><br />
<br><br />
<br />
<p>Deciding on how to utilise our system we had a huge number of potential experiments but decided we would focus our efforts on current and important world health problems. These were narrowed down to; type II diabetes mellitus and, on further research into current events, Ebola. Type II diabetes is a pandemic of epic proportions, on the rise in all corners of the globe of all race and age, in part due to the increase trend in obesity and glucose consumption.</p> <br><br />
<br />
<p></p><br><p><font size="5"><b>America</b></font> <br> <br> <img src="http://img.medscape.com/article/738/271/738271-fig1.jpg" width="370" height="353" /></p><br />
<p> <br> </p> <br> <br><br />
<br />
<p><br><p><font size="5"><b>England</b></font> <br> <br> <img src="http://www.bbc.co.uk/schools/gcsebitesize/science/images/edex_bio_obesity.jpg" width="400" height="353"/></p><br />
<br> <br><br />
<br />
<p></p> <br> <p><font size="5"><b>Comparison by Race</b></font> <br> <br> <img src="http://www.cdc.gov/diabetes/statistics/prev/national/fAgeStandardizedPrevalenceByRaceEthnicitySex.gif"/></p><br />
<p></p> <br> <br />
<br> <br><br />
<p></p> <br> <p><font size="5"><b>Worldwide</b></font> <br> <br> <img src="https://www.sanger.ac.uk/research/projects/metabolicdisease/gfx/metabolicdisease_graph_316x302.png"/></p><br />
<br />
<p>These graphs clearly demonstrate the growing problem posed by diabetes. People of all races, in all corners of the globe are requiring constant monitoring and treatment for this disorder. The treatment require frequent hospital or doctor's appointments and daily injections and/or tablets to relieve the symptoms and damaging effects of diabetes. This costs the healthcare systems in many countries billions of dollars already and could double if those currently living unaware of their condition were to be diagnosed. Almost every individual in America and Europe will have a friend or family member affected with this disease and causes heartache to thousands more following death and pain of sufferers.</p><br />
<p> <br> <br> </p><br />
<p><center><img src="http://i.dailymail.co.uk/i/pix/2014/05/05/article-2620987-1D97B22800000578-267_634x241.jpg" width="75%"/></center></p><br />
<p> <br> <br> </p><br />
<br />
<p>Treatments for Type II diabetes range from the simple; lose weight and consume less sugar to the expensive; gene therapy and dipeptidylpeptidase IV (DPP-IV) inhibitors costing $900 for 90 tablets, and the painful; amputations.<br />
DPP-IV, due to its cellular, genomic origin seemed like an appropriate target to tackle using our system. DPP-IV inhibitors are administered in stage two of treatment directly after lifestyle changes and are used to slow the degradation of incretins such as glucose like peptides which is accelerated by DPP-IV. Incretins act to increase the duration of insulin release and hence increasing the probability of response from the insulin resistant cells. In this way the insulin resistance can in part be masked.</p><p> </p><p></p><p></p><br />
<br />
<p>Gene therapy has been long sought after in biology and has already been implemented as a treatment for many disorders, such as functional CFTR gene therapy in cystic fibrosis sufferers. Its applications are extremely wide ranging, as by manipulating the genome a cell, you can in theory make it carry out the desired function or restore functionality where before there was disfunction. The key difference in our project is that gene therapy focuses on modifying the genome of cells while we are attempting to produce the same effect rather than individual cells on their own. There are many problems with current gene therapy, including it being dangerous and being extremely difficult to perform, is the possibility of modifying the DNA of cells in ways that can't be predicted and causing further issues by altering a necessary gene. Our project is to try and solve some of these problems by using a self replicating RNA strand we termed a 'replicon'. <br />
</p><br />
<p> <br> <br> </p><br />
<p id="what_is_a_replicon?"><b><ins><font size="4">What is a replicon?</b></font></ins> <br> A replicon is RNA that acts to replicate itself on its own using only the ribozymes of the cell. RNA usually degrades very quickly in cells, but a replicon should last permanently, because it should replicate faster than it can be degraded. Several viruses use replicons as their method of manipulating cells. Our idea is to take parts from the genome of hepatitis C (HCV) and modify it so that instead of doing damage to the body, it 'silences' harmful genes. To do this, we want to add an siRNA sequence to a replicon sequence. siRNA (small interfering RNA) is RNA that contains part of a complimentary nucleotide sequence to a particular RNA sequence to which it associates forming a double stranded RNA fragment. Double stranded RNA is not endogenous to the cell and hence is recognised as foreign by Dicer and RISC, in the process detailed on <a href="https://2014.igem.org/Team:Warwick/Project/Howitworks">How it works</a>. The double stranded RNA is destroyed and RISC retains a form of memory for this sequence and will digest it spontaneously in subsequent exposures. We exploited this protection system to target our unwanted mRNA. <br />
</p> <br />
<br />
p></p> <br> <br><br />
<p id="RNA to Synthetic Biology"><b><ins><font size="4">RNA: Meet iGEM</b></font></ins> <br> /p><br />
<br />
<p> A self-replicating RNA system to produce an siRNA to target mRNA which would otherwise give rise to a deregulated protein is just one of the many applications of our system. We purposely as a team created a set of core parts and promoters, essentially creating a tool kit which allows any future iGEM team or researcher to take and use in their own system. This plug and play modularity is at the heart and soul of our motivation to give something to the synthetic biology community. We have the RNA dependent RNA polymerase, which propagates RNA templates. We have the aptazyme kill switch, which ensures regulation of our system or any system, the promoters, the terminators, the testing modules - you name it, we've most likely got it. We hope the synthetic biology community will appreciate our efforts, as RNA increases in use and popularity. DNA is best served as a template for information storage. RNA is multi-functional, catalytic and dynamic, welcome to our world - the RNA world. </p> <br />
<br />
<br />
<p></p> <br> <br><br />
<p id="What_are_the_advantages_of_this_over_conventional_gene_therapy?"><b><ins><font size="4">What are the advantages of this over conventional gene therapy?</b></font></ins> <br> Nowhere in this process is the actual DNA of the cell modified, so this removes the danger of DNA of the cell being modified in a way that is unwanted. This of course, prevents the problem of insertional mutagenesis with viral vectors that routinely integrate into the genome. <br />
<br />
This also improves upon conventional gene silencing, which involves siRNA only, as the replicon represents a permanent source of siRNA, greatly increasing the efficiency of the gene silencing. Our proposed method of delivery is to use a viral vector, technology which does exist but currently is limited in respect to specificity to particular cell types, avoiding recognition by the immune response and efficiency of uptake of the viral vector. In the future, we hope that someone may stumble across our idea and build upon it, so that the full potential of our system can be realized. </p><br />
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<li style="list-style-type: none;"><a href="#Motivation"><span class="tocnumber">1. </span><span class="toctext">Motivation</span></a></li><br />
<li style="list-style-type: none;"><a href="#what_is_a_replicon?"><span class="tocnumber">2. </span><span class="toctext">What is a replicon?</span></a></li><br />
<li style="list-style-type: none;"><a href="#What_are_the_advantages_of_this_over_conventional_gene_therapy?"><span class="tocnumber">3. </span><span class="toctext">What are the advantages of this over conventional gene therapy?</span></a></li><br />
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<p id="Motivation"><b><ins><font size="4">MOTIVATION</b></font></ins> <br><br />
After much deliberation over many project ideas, either expanding on previous projects or alternative substrates for existing parts, we decided we wanted to open up a whole new world of opportunities for Synthetic Biology. Developing the basics for a new realm in the field of RNA. Using a combination of experiments in Escherichia coli (E.coli) and human cells, both HeLa and Huh7.5 we attempted to turn on the lights to RNA world experimentation.<br><img src="https://static.igem.org/mediawiki/parts/b/bc/RNA_strnad.PNG" width="900px"/></p><br />
<br />
<p>Until now RNA has been used sparingly in iGEM with teams tiptoeing around the idea with little advancement. We wanted to set the groundwork for future teams to have the option of classical Synthetic Biology i.e. DNA projects or new projects in RNA world. We feel this is a hugely exciting new area for research to begin as we were initially struggling with originality of our project due to the exponential increase in iGEM teams and projects done previously and underway. RNA is a fascinating alternative for projects. We decided the fundamentals were: an RNA repressor, promoter, ribosome binding site (RBS), kill switch, a replication system and demonstrating the potentials with our own part. These were combined into a self-replicating RNA strand or “Replicon”. These demonstrate a use of all the elements together however the potential permutations and adaptations of these parts are endless.</p> <br><br />
<br><br />
<br />
<p>Deciding on how to utilise our system we had a huge number of potential experiments but decided we would focus our efforts on current and important world health problems. These were narrowed down to; type II diabetes mellitus and, on further research into current events, Ebola. Type II diabetes is a pandemic of epic proportions, on the rise in all corners of the globe of all race and age, in part due to the increase trend in obesity and glucose consumption.</p> <br><br />
<br />
<p></p><br><p><font size="5"><b>America</b></font> <br> <br> <img src="http://img.medscape.com/article/738/271/738271-fig1.jpg" width="370" height="353" /></p><br />
<p> <br> </p> <br> <br><br />
<br />
<p><br><p><font size="5"><b>England</b></font> <br> <br> <img src="http://www.bbc.co.uk/schools/gcsebitesize/science/images/edex_bio_obesity.jpg" width="400" height="353"/></p><br />
<br> <br><br />
<br />
<p></p> <br> <p><font size="5"><b>Comparison by Race</b></font> <br> <br> <img src="http://www.cdc.gov/diabetes/statistics/prev/national/fAgeStandardizedPrevalenceByRaceEthnicitySex.gif"/></p><br />
<p></p> <br> <br />
<br> <br><br />
<p></p> <br> <p><font size="5"><b>Worldwide</b></font> <br> <br> <img src="https://www.sanger.ac.uk/research/projects/metabolicdisease/gfx/metabolicdisease_graph_316x302.png"/></p><br />
<br />
<p>These graphs clearly demonstrate the growing problem posed by diabetes. People of all races, in all corners of the globe are requiring constant monitoring and treatment for this disorder. The treatment require frequent hospital or doctor's appointments and daily injections and/or tablets to relieve the symptoms and damaging effects of diabetes. This costs the healthcare systems in many countries billions of dollars already and could double if those currently living unaware of their condition were to be diagnosed. Almost every individual in America and Europe will have a friend or family member affected with this disease and causes heartache to thousands more following death and pain of sufferers.</p><br />
<p> <br> <br> </p><br />
<p><center><img src="http://i.dailymail.co.uk/i/pix/2014/05/05/article-2620987-1D97B22800000578-267_634x241.jpg" width="75%"/></center></p><br />
<p> <br> <br> </p><br />
<br />
<p>Treatments for Type II diabetes range from the simple; lose weight and consume less sugar to the expensive; gene therapy and dipeptidylpeptidase IV (DPP-IV) inhibitors costing $900 for 90 tablets, and the painful; amputations.<br />
DPP-IV, due to its cellular, genomic origin seemed like an appropriate target to tackle using our system. DPP-IV inhibitors are administered in stage two of treatment directly after lifestyle changes and are used to slow the degradation of incretins such as glucose like peptides which is accelerated by DPP-IV. Incretins act to increase the duration of insulin release and hence increasing the probability of response from the insulin resistant cells. In this way the insulin resistance can in part be masked.</p><p> </p><p></p><p></p><br />
<br />
<p>Gene therapy has been long sought after in biology and has already been implemented as a treatment for many disorders, such as functional CFTR gene therapy in cystic fibrosis sufferers. Its applications are extremely wide ranging, as by manipulating the genome a cell, you can in theory make it carry out the desired function or restore functionality where before there was disfunction. The key difference in our project is that gene therapy focuses on modifying the genome of cells while we are attempting to produce the same effect rather than individual cells on their own. There are many problems with current gene therapy, including it being dangerous and being extremely difficult to perform, is the possibility of modifying the DNA of cells in ways that can't be predicted and causing further issues by altering a necessary gene. Our project is to try and solve some of these problems by using a self replicating RNA strand we termed a 'replicon'. <br />
</p><br />
<p> <br> <br> </p><br />
<p id="what_is_a_replicon?"><b><ins><font size="4">What is a replicon?</b></font></ins> <br> A replicon is RNA that acts to replicate itself on its own using only the ribozymes of the cell. RNA usually degrades very quickly in cells, but a replicon should last permanently, because it should replicate faster than it can be degraded. Several viruses use replicons as their method of manipulating cells. Our idea is to take parts from the genome of hepatitis C (HCV) and modify it so that instead of doing damage to the body, it 'silences' harmful genes. To do this, we want to add an siRNA sequence to a replicon sequence. siRNA (small interfering RNA) is RNA that contains part of a complimentary nucleotide sequence to a particular RNA sequence to which it associates forming a double stranded RNA fragment. Double stranded RNA is not endogenous to the cell and hence is recognised as foreign by Dicer and RISC, in the process detailed on <a href="https://2014.igem.org/Team:Warwick/Project/Howitworks">How it works</a>. The double stranded RNA is destroyed and RISC retains a form of memory for this sequence and will digest it spontaneously in subsequent exposures. We exploited this protection system to target our unwanted mRNA. <br />
</p> <br />
<br />
p></p> <br> <br><br />
<p id="RNA to Synthetic Biology"><b><ins><font size="4">What are the</b></font></ins> <br> /p><br />
<br />
<p></p> <br> <br><br />
<p id="What_are_the_advantages_of_this_over_conventional_gene_therapy?"><b><ins><font size="4">What are the advantages of this over conventional gene therapy?</b></font></ins> <br> Nowhere in this process is the actual DNA of the cell modified, so this removes the danger of DNA of the cell being modified in a way that is unwanted. This of course, prevents the problem of insertional mutagenesis with viral vectors that routinely integrate into the genome. <br />
<br />
This also improves upon conventional gene silencing, which involves siRNA only, as the replicon represents a permanent source of siRNA, greatly increasing the efficiency of the gene silencing. Our proposed method of delivery is to use a viral vector, technology which does exist but currently is limited in respect to specificity to particular cell types, avoiding recognition by the immune response and efficiency of uptake of the viral vector. In the future, we hope that someone may stumble across our idea and build upon it, so that the full potential of our system can be realized. </p><br />
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<h1>Project Specific Changes</h1> <br> </br> <br />
<p>As part of the project we looked to spread synthetic biology throughout the community. We approached this feat through several different avenues.</p><br />
<br> </br> <br />
Our project came into fruition after extensive debate and discussion, the idea of introducing a mechanism by which RNA can be propagated is both conceptually and theoretically appealing. Using our replicon system to target production of a siRNA directed against a target (DPP-IV) shows just one of many applications that our system holds. <br />
Initially, it was not so straight forward when considering additional elements that we might require – for safety of the system was not on our minds. However, after due deliberation we decided to embark and ask questions and most importantly, seek answers. <br />
We started small and simple, with the obvious question on how people perceive our system? <br />
<br />
We decided to conduct a Q + A session, in which academics, students and the wider public were in attendance. Whilst lost of interesting questions were asked, we collectively became stuck when faced with the following question: <br />
<br />
<br> <p> What have you done to ensure your system is safe? </p> </br><br />
<br />
<br> <p> Having reflected on this question, we realized that we failed to consider how our system would be safe - as one of the main applications of our system was to help treat Diabetes, we had to re-think and go back to the drawing board. We came up with two ideas which we feel will greatly improve the safety, but also the efficiency of our system </p> </br> <br />
<br />
<br> <p> Aptazyme </p> </br> <br />
<br />
<br> <p> We decided to use a theophylline induced aptazyme, this essentially acts as a kill-switch if our system becomes unstable - it is possible to cleave our siRNA transcript and prevent our system from functioning. A general descriptor for the Aptazyme is below: </p> </br> <br />
<br />
<br> <p> An aptazyme is an RNA based switch that operates by ribozyme-mediated cleavage of RNA. This part derives from Hartig et al., 2002 and requires the addition of theophylline to induce hammerhead ribozyme activation and cleavage, as depicted in Figure 1a. The part sequence is modified to contain a stop codon at the end, as an RBS is present. </p> </br> <br />
<br />
<br />
<br> <img class = "floatright" src="https://static.igem.org/mediawiki/2014/b/b5/Aptazyme.png " width="500" height="400" align="left" > </br> <br />
<br />
<br> <p> In addition, we introduced another safety device, essentially this would rate limit the level of RNA dependent RNA polymerase (RdRp) production. Our design of RNA dependent RNA polymerase essentially incorporated an MS2 bacteriophage coat protein, linked via a P2A linker protein. A general descriptor for the part we used is below: <br />
MS2 bacteriophage coat protein part derives from Fussenegger et al., 2012. The MS2 coat protein binds a specific stem-loop structure, referred to as the MS2 box. This acts as a silencing mechanism of RNA through translational repression (Ni et al., 1995). The full sequence found in Fussenegger et al., 2012 has been retained, as previous analysis has indicated alteration of MS2 coat protein reduces cooperative protein-RNA binding (Uhlenbeck et al., 1995). MS2 is also frequently used in biochemical purification of RNA-protein complexes and is combined with GFP to detect RNA in living cells. <br> </p> <br />
<br />
<br> <img class = "floatright" src="https://static.igem.org/mediawiki/2014/6/64/Ms2.png" width="500" height="400" align="left" > </br> <br />
<br />
<br> <p> In the end, we were glad to have used and created two new parts for the iGEM registry - these parts ensure that any system similar to ours can be controlled. Check out the parts pages for more information on both the Aptazyme and the MS2 protein. We were very happy with the responses that we received when giving a SynBioCDT for new and upcoming PhD students - with the general consensus that our system looked both promising and safe. </br> </p> <br />
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<h1>Project Specific Changes</h1> <br> </br> <br />
<p>As part of the project we looked to spread synthetic biology throughout the community. We approached this feat through several different avenues.</p><br />
<br> </br> <br />
Our project came into fruition after extensive debate and discussion, the idea of introducing a mechanism by which RNA can be propagated is both conceptually and theoretically appealing. Using our replicon system to target production of a siRNA directed against a target (DPP-IV) shows just one of many applications that our system holds. <br />
Initially, it was not so straight forward when considering additional elements that we might require – for safety of the system was not on our minds. However, after due deliberation we decided to embark and ask questions and most importantly, seek answers. <br />
We started small and simple, with the obvious question on how people perceive our system? <br />
<br />
We decided to conduct a Q + A session, in which academics, students and the wider public were in attendance. Whilst lost of interesting questions were asked, we collectively became stuck when faced with the following question: <br />
<br />
<br> <p> What have you done to ensure your system is safe? </p> </br><br />
<br />
<br> <p> Having reflected on this question, we realized that we failed to consider how our system would be safe - as one of the main applications of our system was to help treat Diabetes, we had to re-think and go back to the drawing board. We came up with two ideas which we feel will greatly improve the safety, but also the efficiency of our system </p> </br> <br />
<br />
<br> <p> Aptazyme </p> </br> <br />
<br />
<br> <p> We decided to use a theophylline induced aptazyme, this essentially acts as a kill-switch if our system becomes unstable - it is possible to cleave our siRNA transcript and prevent our system from functioning. A general descriptor for the Aptazyme is below: </p> </br> <br />
<br />
<br> <p> An aptazyme is an RNA based switch that operates by ribozyme-mediated cleavage of RNA. This part derives from Hartig et al., 2002 and requires the addition of theophylline to induce hammerhead ribozyme activation and cleavage, as depicted in Figure 1a. The part sequence is modified to contain a stop codon at the end, as an RBS is present. </p> </br> <br />
<br />
<br />
<br> <img class = "floatright" src="https://static.igem.org/mediawiki/2014/b/b5/Aptazyme.png " width="500" height="400" align="left" > </br> <br />
<br />
<br> <p> In addition, we introduced another safety device, essentially this would rate limit the level of RNA dependent RNA polymerase (RdRp) production. Our design of RNA dependent RNA polymerase essentially incorporated an MS2 bacteriophage coat protein, linked via a P2A linker protein. A general descriptor for the part we used is below: <br />
MS2 bacteriophage coat protein part derives from Fussenegger et al., 2012. The MS2 coat protein binds a specific stem-loop structure, referred to as the MS2 box. This acts as a silencing mechanism of RNA through translational repression (Ni et al., 1995). The full sequence found in Fussenegger et al., 2012 has been retained, as previous analysis has indicated alteration of MS2 coat protein reduces cooperative protein-RNA binding (Uhlenbeck et al., 1995). MS2 is also frequently used in biochemical purification of RNA-protein complexes and is combined with GFP to detect RNA in living cells. <br> </p> <br />
<br />
<br> <img class = "floatright" src="https://static.igem.org/mediawiki/2014/6/64/Ms2.png" width="500" height="400" align="left" > </br> <br />
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<p>Contact information: <a href="mailto:igem.warwick@gmail.com"><br />
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</html></div>Waqarhttp://2014.igem.org/Team:Warwick/Human/ChangesTeam:Warwick/Human/Changes2014-10-17T21:18:55Z<p>Waqar: </p>
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<!-- THIS IS WHERE YOUR MAIN BODY GOES --><br />
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<br />
<h1>Project Specific Changes</h1> <br> </br> <br />
<p>As part of the project we looked to spread synthetic biology throughout the community. We approached this feat through several different avenues.</p><br />
<br> </br> <br />
Our project came into fruition after extensive debate and discussion, the idea of introducing a mechanism by which RNA can be propagated is both conceptually and theoretically appealing. Using our replicon system to target production of a siRNA directed against a target (DPP-IV) shows just one of many applications that our system holds. <br />
Initially, it was not so straight forward when considering additional elements that we might require – for safety of the system was not on our minds. However, after due deliberation we decided to embark and ask questions and most importantly, seek answers. <br />
We started small and simple, with the obvious question on how people perceive our system? <br />
<br />
We decided to conduct a Q + A session, in which academics, students and the wider public were in attendance. Whilst lost of interesting questions were asked, we collectively became stuck when faced with the following question: <br />
<br />
<br> <p> What have you done to ensure your system is safe? </p> </br><br />
<br />
<br> <p> Having reflected on this question, we realized that we failed to consider how our system would be safe - as one of the main applications of our system was to help treat Diabetes, we had to re-think and go back to the drawing board. We came up with two ideas which we feel will greatly improve the safety, but also the efficiency of our system </p> </br> <br />
<br />
<br> <p> Aptazyme </p> </br> <br />
<br />
<br> <p> We decided to use a theophylline induced aptazyme, this essentially acts as a kill-switch if our system becomes unstable - it is possible to cleave our siRNA transcript and prevent our system from functioning. A general descriptor for the Aptazyme is below: </p> </br> <br />
<br />
<br> <p> An aptazyme is an RNA based switch that operates by ribozyme-mediated cleavage of RNA. This part derives from Hartig et al., 2002 and requires the addition of theophylline to induce hammerhead ribozyme activation and cleavage, as depicted in Figure 1a. The part sequence is modified to contain a stop codon at the end, as an RBS is present. </p> </br> <br />
<br />
<br />
<br> <img class = "floatright" src="https://static.igem.org/mediawiki/2014/b/b5/Aptazyme.png " width="500" height="400" align="right" > </br> <br />
<br />
<br> <p> In addition, we introduced another safety device, essentially this would rate limit the level of RNA dependent RNA polymerase (RdRp) production. Our design of RNA dependent RNA polymerase essentially incorporated an MS2 bacteriophage coat protein, linked via a P2A linker protein. A general descriptor for the part we used is below: <br />
MS2 bacteriophage coat protein part derives from Fussenegger et al., 2012. The MS2 coat protein binds a specific stem-loop structure, referred to as the MS2 box. This acts as a silencing mechanism of RNA through translational repression (Ni et al., 1995). The full sequence found in Fussenegger et al., 2012 has been retained, as previous analysis has indicated alteration of MS2 coat protein reduces cooperative protein-RNA binding (Uhlenbeck et al., 1995). MS2 is also frequently used in biochemical purification of RNA-protein complexes and is combined with GFP to detect RNA in living cells. <br> </p> <br />
<br />
<br> <img class = "floatright" src="https://static.igem.org/mediawiki/2014/6/64/Ms2.png" width="500" height="400" align="right" > </br> <br />
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<p>Created by: iGEM Warwick</p><br />
<p>Contact information: <a href="mailto:igem.warwick@gmail.com"><br />
igem.warwick@gmail.com</a></p><br />
</footer><br />
</html></div>Waqarhttp://2014.igem.org/File:Ms2.pngFile:Ms2.png2014-10-17T21:17:46Z<p>Waqar: </p>
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<li> <a href = "/Team:Warwick/Human/Outreach"> OUTREACH </a> </li><br />
<li> <a href = "/Team:Warwick/Human/Bioweapons"> BIOWEAPONS </a> </li><br />
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<!-- THIS IS WHERE YOUR MAIN BODY GOES --><br />
<br />
<br />
<br />
<h1>Project Specific Changes</h1> <br> </br> <br />
<p>As part of the project we looked to spread synthetic biology throughout the community. We approached this feat through several different avenues.</p><br />
<br> </br> <br />
Our project came into fruition after extensive debate and discussion, the idea of introducing a mechanism by which RNA can be propagated is both conceptually and theoretically appealing. Using our replicon system to target production of a siRNA directed against a target (DPP-IV) shows just one of many applications that our system holds. <br />
Initially, it was not so straight forward when considering additional elements that we might require – for safety of the system was not on our minds. However, after due deliberation we decided to embark and ask questions and most importantly, seek answers. <br />
We started small and simple, with the obvious question on how people perceive our system? <br />
<br />
We decided to conduct a Q + A session, in which academics, students and the wider public were in attendance. Whilst lost of interesting questions were asked, we collectively became stuck when faced with the following question: <br />
<br />
<br> <p> What have you done to ensure your system is safe? </p> </br><br />
<br />
<br> <p> Having reflected on this question, we realized that we failed to consider how our system would be safe - as one of the main applications of our system was to help treat Diabetes, we had to re-think and go back to the drawing board. We came up with two ideas which we feel will greatly improve the safety, but also the efficiency of our system </p> </br> <br />
<br />
<br> <p> Aptazyme </p> </br> <br />
<br />
<br> <p> We decided to use a theophylline induced aptazyme, this essentially acts as a kill-switch if our system becomes unstable - it is possible to cleave our siRNA transcript and prevent our system from functioning. A general descriptor for the Aptazyme is below: </p> </br> <br />
<br />
<br> <p> An aptazyme is an RNA based switch that operates by ribozyme-mediated cleavage of RNA. This part derives from Hartig et al., 2002 and requires the addition of theophylline to induce hammerhead ribozyme activation and cleavage, as depicted in Figure 1a. The part sequence is modified to contain a stop codon at the end, as an RBS is present. </p> </br> <br />
<br />
<br />
<img class = "floatright" src="https://static.igem.org/mediawiki/2014/b/b5/Aptazyme.png " width="500" height="400" align="right" ><br />
<br />
<br> <p> In addition, we introduced another safety device, essentially this would rate limit the level of RNA dependent RNA polymerase (RdRp) production. Our design of RNA dependent RNA polymerase essentially incorporated an MS2 bacteriophage coat protein, linked via a P2A linker protein. A general descriptor for the part we used is below: <br />
MS2 bacteriophage coat protein part derives from Fussenegger et al., 2012. The MS2 coat protein binds a specific stem-loop structure, referred to as the MS2 box. This acts as a silencing mechanism of RNA through translational repression (Ni et al., 1995). The full sequence found in Fussenegger et al., 2012 has been retained, as previous analysis has indicated alteration of MS2 coat protein reduces cooperative protein-RNA binding (Uhlenbeck et al., 1995). MS2 is also frequently used in biochemical purification of RNA-protein complexes and is combined with GFP to detect RNA in living cells. <br> </p> <br />
<br />
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<br />
<!--CONTENT END--><br />
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<p>Contact information: <a href="mailto:igem.warwick@gmail.com"><br />
igem.warwick@gmail.com</a></p><br />
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</html></div>Waqar