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− | <h1>Contributions in circuit design,safety control and modeling</h1> | + | <h1 tabIndex="1">Full contributions to future teams</h1> |
| <div class="column full_size"> | | <div class="column full_size"> |
− | <p>Our team has made innovations in the design of CBP expressing circuits, quorum sensing and kill switch, based on existing literature and iGEM projects. We also adapt our modeling to simulate how our systems work. We hope this will make contributions to future teams.</p> | + | <p>Updated on 2020-11-22: we won the Gold Medal.</p> |
− | </div>
| + | <p>Our team has made contributions to the iGEM community in all aspects. And here is the list.</p></div> |
| + | <ul> |
| + | <li>For education, we offer popular biological science courses for the general public, paying attention to the elderly who were ignored previously. We promoted and are promoting educational equity.</li> |
| | | |
− | <div class="clear extra_space"></div><!-- 一个章节结束需要clear来留白 如果觉得内容间差异大再加上extra_space -->
| + | <li>For human practice and entrepreneurship, we improved our project's progress through communications and eventually formed a complete business plan. Once we secured investments and successfully developed the product, we can supply the elderly with a low-priced and useful calcium supplement product. As a typical case of the combination of scientific research, teaching, and industrialization driven by iGEM, our experience serves as guidance on how undergraduates play their roles in the product development.</li> |
| | | |
− | <h2>CBP expressing system</h2>
| + | <li>For modeling, we improved the quorum-sensing model from the past, using the Gillespie algorithm random simulation to simulate the physiological processes at macro and micro levels. We explained the dynamic stability of the antimicrobial peptide. For the Kill Switch model, we improved the logistic equation based on the previous experimental data, adjusted the promoter properties according to literature, and made sensitivity analysis. Our approach can be generlized and used by future teams.</li> |
| | | |
− | <div>
| + | <li>For safety, we surveyed the existing kill switches in the literature and modeled key properties of the cold triggered kill switch, providing an experimental plan for further use.</li> |
− | <p>Osteoporosis and other diseases caused by calcium deficiency are common problems for people, especially the elderly in many areas. CBP (calcium-binding peptide) refers to a class of oligopeptides that are capable of chelating calcium. They promote Calcium uptake in Caco-2 cells, which can help solve the problem of calcium deficiency. Since these oligopeptides are derived from natural plant or animal food, they are biologically safe.</p> | + | |
− | <p>According to some literature, we learned that the entire sequence of the CBP expression peptide contains five different calcium-binding peptides, which are all experimentally proved to significantly increase calcium absorption in vivo or in vitro. The calcium ion spontaneously binds to the Asp or Glu residue, allowing the calcium-peptide complex to promote calcium influx into intestinal epithelial cells. The oligopeptide sequence is expressed as a complete peptide in the engineered bacteria and will be cleaved into functional oligopeptides in the presence of digestive enzymes in the intestinal lumen.</p>
| + | |
− | <p>2019 Fudan team tried to make the expression of lactase in intestines controllable to treat lactose intolerance, based on which we establish a safe CBP expression system in Escherichia coli, providing a solution to increase calcium intake.</p>
| + | |
− | <p>We have added new parts to the Registry of Parts and conducted experiments to provide new experimental data on the expression of CBP in E. coli, providing references for future teams to use the expression system.</p>
| + | |
− | <p>This work is completed by our team members Lu Yiyang and Zhang Zhenru. Enter the team page to learn more about our team members.</p>
| + | |
− | </div>
| + | |
− | <div class="clear"></div><!-- 一个章节结束需要clear来留白 -->
| + | |
| | | |
− | <h2>Quorum sensing system</h2>
| + | <li>For basic parts and composite parts:<br/> |
| + | (1) We combined scattered information in the literature and created our own CaAP (calcium absorption peptide). We showed it could be secreted and has the ability to bind calcium. Then we had it expressed controllably in <i>E. coli </i> to help intestinal cells absorb calcium.<br/> |
| + | (2) We increase the secretion of antimicrobial peptides by adopting a relatively low expression of antimicrobial peptides (mcbABCD) and high expression of the antimicrobial peptide immune portion (mcbEFG), which improved our quorum system efficiency.</li> |
| | | |
− | <div>
| + | <li>For parts collection, we provided a complete set of plasmids we used to optimize circuits for expressing probiotic secreted proteins. Our experiences and results were carefully documented on the Parts Registry, which makes it easy for others to use. Our contribution shows that we are committed to putting ideas of synthetic biology into practice, including engineering and knowledge sharing.</li> |
− | <p>The quorum-sensing system makes the bacterial proliferation regulated by its colony number, ensuring safe and controllable growth in human bodies.</p> | + | |
− | <p>In our project, we take advantage of the quorum-sensing system of luxI/luxR and the antimicrobial peptide expressing system to control the number of bacteria and open the CBP expressing system at the proper time. You can find more details on relative pages.</p>
| + | |
− | <p>Fudan 2019 team proposed the antimicrobial peptide quorum-sensing system. The expression effect of the antimicrobial peptide system determines whether the flora can colonize as soon as possible and achieve the balance of quorum sensing. The antimicrobial peptide expressing system didn't work favorably last year, so this design still needs feasibility proof. We read the wiki and found that the antibacterial test of the antimicrobial peptide effect failed to achieve a satisfactory effect. Through team communication, we doubt that it might attribute to the low secretion of an antimicrobial peptide.</p>
| + | |
− | <p>Therefore, we proposed an improved plan, using low-copy plasmids to reduce the expression burden of engineered bacteria, and adopting a relatively low expression of antimicrobial peptides (mcbA-D) and high expression of the antimicrobial peptide immune portion (mcbE-G) to achieve high secretion of antimicrobial peptides. Through the high expression of channel protein and immune protein to promote the excretion of antimicrobial peptides from the bacteria, we reduce the Microcin accumulation in them, thereby inducing our bacteria to produce more antimicrobial peptides. That's how we achieve our purpose of dynamically and moderately regulating the intensity of antimicrobial peptide expression.</p>
| + | |
− | <p>Specifically, we make improvements from the following two aspects:</p>
| + | |
− | <p>First, improve the mcbE-G promoter ptetR to achieve a high expression of mcbE-G. We decide to create fusion promoters that few have tried before, fusing the upstream of -35 site, -35~-10 sites, downstream of -10 site, sites near RBS and other proportions of the strong pI promoter in lambda phage with the tetracycline operon tetO. We expect to obtain two new fusion promoters ptetO2 and ptetO3, and try to find the best expression state by changing the number of tetO operons. From the experimental data of the literature, we have learned that these two promoters have low-leakage characteristics, and their peak intensity reaches about 4 times compared with placZ, ensuring a high expression level.</p>
| + | |
− | <p>Second, screen a suitable expression promoter for mcbA-D. Since the mcbA-D gene expresses the toxic part of the antimicrobial peptide, an appropriate promoter strength can ensure the expression effect of the antimicrobial peptide without causing excessive expression burden. We used a set of deeply optimized promoters of different strengths for experiments, constructed multiple systems, and screened 14 promoters to obtain 6 promoters suitable for the expression of antimicrobial peptides in E. coli.</p>
| + | |
− | <p>We can now stably express antimicrobial peptides and overexpress their channel proteins through the above two improvements. Existing literature proves that increasing the expression of channel protein in high-yield or even wild-type bacteria can significantly increase the production of antibiotics. As the copy number of channel protein increases, it can be detected that the ratio of extracellular to intracellular antibiotics increases, which means discharge efficiency increases. You can find the specific reason analysis on relevant pages.</p>
| + | |
− | <p>This improvement not only continues the design of Fudan 2019 team and helps prove the feasibility of this quorum-sensing system, but also facilitates future teams to use this system to control the multiplication of flora. Besides, the methods of obtaining high-expression and low-leakage fusion promoters and constructing a system to screen suitable strength promoters also provide new effective ideas for regulating gene expression efficiently.</p>
| + | |
− | <p>We can provide reliable experimental data about related parts, which confirms the feasibility of this quorum-sensing system and also provides reference information for future teams who use the system. For details, read the relevant pages.</p>
| + | |
− | <p>This contribution is made by our team members Li Mingwei and Zhang Gaochen. You can enter the team page to learn more about the team members.</p>
| + | |
− | </div>
| + | |
− | <div class="clear"></div><!-- 一个章节结束需要clear来留白 -->
| + | |
| | | |
− | <h2>Kill switch</h2>
| + | <li>For measurement, we developed a method to measure blood calcium. We also made simple hardware using low-cost LED tubes and an existing mobile phone software, hoping to design a user-friendly detector for the elderly.</li> |
| + | </ul> |
| | | |
− | <div> | + | <div class="clear extra_space"></div><!-- 一个章节结束需要clear来留白 如果觉得内容间差异大再加上extra_space --> |
− | <p>Kill switches can be classified by their functions, including controlling the density of flora, protecting users, protecting the environment, etc. Among them, the environment-friendly kill switch is a genetic circuit that promotes the death of the engineered bacteria when they leave the environment where the designer expects it to work. In the intestine, a probiotic kill switch is frequently used to prevent the modified gene from leaking into the environment when probiotics are released. </p> | + | |
− | <p>The kill switch in our project this year applies the toxin-antitoxin system, in which the toxin relE is constantly expressed, while the antitoxin relB is expressed only at body temperature(37℃), which protects the engineered bacteria from toxin. When the environment temperature is lower than 37℃, the antitoxin expression decreases, and the engineered bacteria die. We obtain the data from 19BNU-China for modeling verification. You can read relevant pages for details.</p>
| + | <h2>Education</h2> |
− | <p>This kill switch has significant advantages compared to 2019 Fudan team. Last year their kill switch reaches the best killing effect at 40°C instead of 37℃, not suitable for our goal. But this year we make it. It allows the bacteria to survive at 37℃ but suicide when the temperature decrease, which is more suitable for working in the internal environment of the human body. Moreover, last year they had to express a variety of proteins to complete the process of temperature control, which caused the bacteria survival burden heavier. </p> | + | <div class="column full_size"> |
− | <p>Fortunately, now our kill switch contains fewer essential proteins,helping the bacterial flora stably express genes we insert.
| + | <p>We realized that understanding of biological knowledge varies among different groups of people, so we decided to create new access to basic knowledge for them. We regularly make brief and easy-to-understand biological online audio courses, including audio and text with illustrations, starting from the most basic macromolecules concept. Then we put them on platforms like WeChat, Ximalaya, <i>etc</i>. This allows people who have never been exposed to synthetic biology before, even children and the elderly who were ignored before, to have a preliminary understanding of what we can do through synthetic biology. You can read <a href="/Team:Fudan/Education">/Team:Fudan/Education</a> for more details.</p> |
− | Besides, our kill switch has a more sensitive temperature response and higher efficiency than 19BNU-China.
| + | <p>These popular science materials are available to everyone. They can be released and applied to the public-facing popular science propaganda in our region so that the public and us can reach a consensus on the value of synthetic biology. The sharing of resources also enables more people to participate in our work, collectively to promoting social education equity and development.</p> |
− | We also selected various existing kill switches based on a kill switch database established by 2016 Marlborough team. We analyze and summarize suicide trigger conditions and killing mechanisms of these kill switches, citing the kill switches used by previous teams as examples for reference. This will help future teams to better understand the killing effect and applicable scope of various kill switches. And they could choose the appropriate kill switch according to their own needs to achieve the purpose of experimental safety.</p>
| + | <p><br/>This contribution was mainly made by our team member Yiyang. You can go to our <a href="/Team:Fudan/Team#YaoYY">Team page</a> to learn more about her.</p> |
− | <p>For detailed illustration, please read the Safety page.</p> | + | |
− | <p>This contribution is made by our team member Zhang Jingqi. You can enter the team page to learn more about our team members.</p>
| + | |
| </div> | | </div> |
| <div class="clear"></div><!-- 一个章节结束需要clear来留白 --> | | <div class="clear"></div><!-- 一个章节结束需要clear来留白 --> |
| | | |
− | <h2>Modeling</h2> | + | <h2>Entrepreneurship</h2> |
− |
| + | <div class="column full_size"> |
− | <div> | + | <p>We promoted our project's progress through communications and eventually formed a complete business plan for the next five years. We hope to gain multiple rounds of investments, successfully developed the product and get official approval for public sale over the counter. Our ultimate goal is to make it reach the elderly in the underdeveloped countries. At that time, we can supply the elderly all over the world with a low-priced and sustainable calcium supplement product.</p> |
− | <p>The experimental design, which increases the expression of McbE-G (efflux and immune proportion) and decreases the expression of McbA-D(toxicity proportion), promotes the expression of antimicrobial peptides by changing the concentration balance of substances. The McbEF expression is controlled by the ptetR promoter. </p> | + | <p>Our commercial projects is a successful combination of scientific research, teaching, and industrialization driven by iGEM. We sincerely hope that our experience can serve as guidance on how undergraduates play their roles in the project, promoting the transformation of scientific research results into commercial products.</p> |
− | <p>The system above can be described by the Hill equation. Since the promoter has been improved, the corresponding modeling is also corrected to show the changes in the switch sensitivity of the quorum-sensing system and the expression of antimicrobial peptides.</p>
| + | |
− | <p>In the kill switch section, we improved the toxin-antitoxin system of Team 19BNU-China, replacing the riboswitch from RNA thermometer FourU to RNA thermometer NoChill-06, which is more efficient. We also improved UCAS's modeling of similar systems. Based on the original modeling, we add a comparison of the system expression with or without the temperature-controlled kill switch.</p> | + | <p><br/>This contribution was mainly made by our team member Tianqi. You can go to our <a href="/Team:Fudan/Team#MoEmily">Team page</a> to learn more about her.</p> |
− | <p>These mathematical models can provide future teams with more information about the effects of the quorum-sensing system and kill switch system. For details, please visit the Modeling pages.</p> | + | |
− | <p>This contribution is mainly made by our team member Jiang Xiaohui. You can enter the team page to learn more about our team members.</p>
| + | |
| </div> | | </div> |
| <div class="clear"></div><!-- 一个章节结束需要clear来留白 --> | | <div class="clear"></div><!-- 一个章节结束需要clear来留白 --> |
| | | |
| <h2>Modeling</h2> | | <h2>Modeling</h2> |
− | <div class="column third_size"> | + | <div class="column full_size"> |
− | <img src="https://static.igem.org/mediawiki/2020/8/8b/T--Fudan--map_2.svg" alt="map of calcium intake" /> | + | <p>We have established two models: quorum sensing process model and kill switch model. </p></div> |
− | </div>
| + | <div class="column full_size"> |
− | <div class="column two_thirds_size">
| + | <h4>Quorum sensing</h4> |
− | <p>在宽屏,这部分内容占页面1/3;窄屏就是全幅。添加了column同时 图1/3 + 字2/3 正好宽屏的一幅。 China has an estimated 70 million osteo
| + | <p>In the quorum sensing model, we used the Gillespie algorithm in random simulation to simulate the macro and micro levels' physiological functions. It expresses luxI and luxR genes at the micro level and produces dimers before the population reaches a specific size. At the macro level, <i>Escherichia coli</i> keeps proliferating, excreting antimicrobial peptides, and colonizing the intestinal tract during this process. When the population number is sufficiently large, the short calcium absorbing peptide (CaAP) and the regulation system begin to express, while the antimicrobial peptide is expressed but cannot be discharged so that the bacterial number can achieve dynamic stability. We refer to the model and data of <a href="https://2019.igem.org/Team:Fudan/Model" target="_blank">19Fudan Team</a> and use the random process to describe it more clearly. We modeled the quorum sensing process in various stages and levels. Remarkably, we explained the dynamic stability of McbA.</p></div> |
− | porosis patien China has an estimated 70 million osteoporosis patien China has an estimated 70 million osteoporosis patienChina has an estimated 70 million oste
| + | |
− | oporosis patienChina has an estimated 70 million osteoporosis patien</p>
| + | |
− | </div>
| + | |
− | <div class="clear"></div><!-- 一个章节结束需要clear来留白 -->
| + | |
| | | |
− | <div class="column full_size"><!-- 全幅面的文字内容,上面是否留白可选 -->
| + | <div class="column full_size"> |
− | <p>However, for the Chinese population, the bottlenecks are
| + | <h4>Kill switch</h4> |
− | as follows:
| + | <p>In the kill switch model, we use <a href="https://static.igem.org/mediawiki/2020/c/ca/T--Fudan--data_from_19BNU.xlsx">19BNU Team</a>'s data. We improved the logistic equation, adjusted the promoter properties and made a sensitivity analysis. We see better results through our effects.</p> |
− | </p>
| + | <p>Our models confirmed the feasibility of <a href="/Team:Fudan/Design">our design</a> to a certain extent and provided valuable references for future teams who are interested in this. Also, we showed the process of adapting the models of previous teams to our new ones, and improving them. We hope this can promote the sharing of inspiration and creativity in the iGEM community.</p> |
− | <ol>
| + | |
− | <li>注意这里列表的写法 页面字会变深 突出内容 ol是编数字的 nts</li>
| + | |
− | <li>calcium-supplementing pills daste</li>
| + | |
− | <li>The body's absorptioes as calcium intake increases</li>
| + | |
− | <li>Vegetables conta列表的写法 页面字会变深 突出内容 ol是编数字的 ul是没有标数字的列表 </li>
| + | |
− | </ol>
| + | |
− | <p>
| + | |
− | However, the currently popular calcium supplement method on the market is either to adjust diet or to consume a lot of calcium supplementing pills. For the elderly, they suffer from poor memory or neglect the importance of calcium pills, often forgetting to consume the supplement; for children, they often refuse to take calcium pills or to maintain some diet high in calcium, thus requiring the "liquid calcium" method to ensure sufficient calcium intake. Ho可以 继续大段内容
| + | |
− | </p>
| + | |
| | | |
| + | <p><br/>This contribution is mainly made by our team member Xiaohui. You can go to our <a href="/Team:Fudan/Team#JiangXH">Team page</a> to learn more about her.</p></div> |
| | | |
− | <div class="highlight decoration_background decoration_A_top">
| + | <div class="clear"></div><!-- 一个章节结束需要clear来留白 --> |
− | <p> | + | |
− | 章节内容的分段就用p开p关,额外需要关注的可以套一个highlight的框,有多种版本
| + | |
− | </p>
| + | |
− | </div>
| + | |
− | <p>
| + | |
− | 章节内容的分段就用p开p关
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− | </p>
| + | |
− | <div class="highlight decoration_B_full"> | + | |
− | <p>
| + | |
− | 章节内容的分段就用p开p关,额外需要关注的可以套一个highlight的框,细看 https://2020.igem.org/Resources/Template_Documentation#highlight
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− | </p>
| + | |
− | </div>
| + | |
− | <p>
| + | |
− | 章节内容的分段就用p开p关
| + | |
− | </p>
| + | |
− | <p>
| + | |
− | 章节内容的分段就用p开p关 <a href="https://URL"> EXAM 外部链接 href尽量使用https </a>
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− | </p>
| + | |
− | <ul>
| + | |
− | <li>注意这里列表的写法 页面字会变深 突出内容 ul是没有标数字的列表 nts</li>
| + | |
− | <li>calcium-supple menting pills don’t haat taste</li>
| + | |
− | <li>Vegetables conta列表的写法 页面字会变深 突出内容 ol是编数字的 ul是没有标数字的列表 </li>
| + | |
− | </ul>
| + | |
− | <p>
| + | |
− | 章节内容的分段就用p开p关
| + | |
− | </p>
| + | |
− | </div><!-- 每个幅面结束都需要 关div -->
| + | |
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− | <div class="clear extra_space"></div><!-- 一个章节结束需要clear来留白 如果觉得内容间差异大再加上extra_space --> | + | <h2>Improved safety with a kill switch</h2> |
| + | <div class="column full_size"> |
| + | <p>An environment-friendly kill switch is a genetic circuit that promotes the death of the engineered bacteria when they leave the environment where the designer expects it to work. In the intestine, a probiotic kill switch is frequently used to prevent the modified gene from leaking into the environment when probiotics are released.</p> |
| + | </div> |
| | | |
− | <h2>又来个章节 sis</h2>
| + | <div class="column half_size"><img src="https://static.igem.org/mediawiki/2020/7/71/T--Fudan--contribution_RelEB2.png" alt="contribution of BBa_K3036004" /></div> |
− | <div class="column full_size">
| + | <div class="column half_size"> |
− | <p>引入文字 ion.</p>
| + | <h4>New information from literature</h4> |
− | <p>Firstly, the product is designed for oral use and our target user is the elderly. 英文分项不需要ol或ul</p>
| + | <p>Built on last year's work, we have added new information learned from the literature that needs attention to RelE/RelB toxin/antitoxin system, which makes the information on <a target="_blank" href="http://parts.igem.org/Part:BBa_K3096001">the Registry page</a> more specific and reliable. We found information about potential pathogenicity of RelE, chromosomally encoded RelE/RelB in gut microbiota, and homonymic "Relb". We regarded these as a must-know for iGEM teams focusing on intestinal probiotics and attempting to use these parts.</p> |
− | <ol>
| + | </div> |
− | <li>The produc</li>
| + | |
− | <li>The short pep</li>
| + | |
− | <li>The expression level of short peptides has a threshold, preventing any excessive calcium absorption that might lead to hypercalcemia 注意句子超长后的回折</li>
| + | |
− | <li>There is a kill swit.</li>
| + | |
− | </ol>
| + | |
| | | |
− | <p>
| + | <div class="clear"></div><!-- 一个章节结束需要clear来留白 --> |
− | Based on relevant research, the product is exp 章节内分段 ina. tien China has an estimated 70 million osteoporosis patien China has an estimated 70 million osteoporosis patienChina has an estimated 70 million oste
| + | |
− | oporosis patienChina has an estimated 70 million osteoporosis pat
| + | |
− | </p>
| + | |
| | | |
− | <p>Compared w 章节内分段 ique advantages tien China has an estimated 70 million osteoporosis patien China has an estimated 70 million osteoporosis patienChina has an estimated 70 million oste
| + | <div class="column half_size"><img src="https://static.igem.org/mediawiki/2020/e/ee/T--Fudan--contribution_RelEB1.png" alt="contribution of BBa_K3036004" /><img src="https://static.igem.org/mediawiki/2020/8/89/T--Fudan--contribution_RelEB3.png" alt="contribution of BBa_K3036004" /></div> |
− | oporosis patienChina has an estimated 70 million osteoporosis pat tien China has an estimated 70 million osteoporosis patien China has an estimated 70 million osteoporosis patienChina has an estimated 70 million oste
| + | |
− | oporosis patienChina has an estimated 70 million osteoporosis pat tien China has an estimated 70 million osteoporosis patien China has an estimated 70 million osteoporosis patienChina has an estimated 70 million oste
| + | |
− | oporosis patienChina has an estimated 70 million osteoporosis pat.
| + | |
− | </p>
| + | |
| | | |
| + | <div class="column half_size"> |
| + | <h4>Improvements and experimental plans</h4> |
| + | <p>The kill switch in our project this year applies the toxin/antitoxin system. The toxin is constantly expressed, while the antitoxin is expressed only at body temperature (37℃), which protects the engineered bacteria from toxin. When the environment temperature is lower than 37℃, the antitoxin expression decreases, and the engineered bacteria die.</p> |
| + | <p>This kill switch has significant advantages compared to <a href="https://2019.igem.org/Team:Fudan/Safety#Project" target="_blank">the one proposed by 19Fudan</a>. Last year, their kill switch reaches the best killing effect at 40°C instead of 37℃, not suitable for intestinal usage. This year we improved it. It allows the bacteria to survive at 37℃ but suicide when the temperature decrease, which is more suitable for working in the internal environment of the human body. Moreover, last year, they had to express a variety of proteins to complete the process of temperature control, which caused the bacteria survival burden heavier. Fortunately, now our kill switch contains fewer essential proteins,helping the bacterial flora stably express genes we insert.</p> |
| + | <p>Besides, our kill switch has a more sensitive temperature response and higher efficiency than the one from 19BNU, since we changed the temperature sensing riboswitch from RNA thermometer <u>FourU</u> to <u>NoChill-06</u>.</p> |
| + | <p>Due to the impact of the pandemic, we have not been able to conduct the confirmatory experiment, but we provide an experimental plan. You can find this on our <a href="/Team:Fudan/Experiments#kill_switch_plan">Experiments page</a>.</p> |
| + | <p>At the same time, we used the original data from 19BNU for modeling verification. More detailed information is showed on our <a href="/Team:Fudan/Model">Modeling page</a>. Modeling proves that the kill switch is theoretically reliable and can be experimentally verified. You can also read the <a href="/Team:Fudan/Engineering">Engineering page</a> for more details.</p> </div> |
| + | |
| + | <div class="clear"></div><!-- 一个章节结束需要clear来留白 --> |
| + | <h4 id="kill_switch_tables">Current available of Kill Switches</h4> |
| + | <p>We obtained valuable information based on <a href="https://2016.igem.org/Team:Marburg/Safety" target="_blank">16Marlborough Team</a>'s Kill Switch database. We traversed mostly used Kill Switches in intestinal probiotics designed by the past iGEM teams. We summarized them into two tables, in which we analyzed trigger conditions and the mechanism of existing Kill Switches. (For parts using resemble mechanism, we only listed the latest and most efficient ones.)</p> |
| + | <h6>Table 1. Summary of the mostly used Killer system in intestinal probiotics project. (More “+” represents higher efficiency.)</h6> |
| <table> | | <table> |
| <tr> | | <tr> |
− | <th> Header 1 这是igem hq的表格的写法 </th> <th> Header 2 </th> | + | <th>Killer System</th><th>Advantages</th><th>Disadvantages</th><th>Parts</th><th>Efficiency</th><th>Comments</th> |
| + | </tr> |
| + | <tr> |
| + | <td>Toxin</td> <td>easy, direct</td><td>the leakage of toxin may cause engineered <i>E. coli</i> lysing in the body and interrupting native flora.</td><td><a target="_blank" href="http://parts.igem.org/Part:BBa_K302033">MazF</a><br/><br/><a target="_blank" href="http://parts.igem.org/Part:BBa_K3096001">Cas3</a><br/><br/><a target="_blank" href="http://parts.igem.org/Part:BBa_K2152004">Phi 174 Gene E protein</a></td><td>+++</td><td>Expression of toxins alone have been shown to help develop bacterial persistence<sup>[2]</sup>.</td> |
| </tr> | | </tr> |
| <tr> | | <tr> |
− | <td> Content A 1 </td> <td> Content B 1 </td> | + | <td>Toxin/antitoxin system</td><td>stable, flexible</td><td>/</td><td><a target="_blank" href="http://parts.igem.org/Part:BBa_K2292002">MazF</a>/<a target="_blank" href="http://parts.igem.org/Part:BBa_K2292002">MazE</a><br/><br/><a target="_blank" href="http://parts.igem.org/Part:BBa_K185047">RelE</a>/<a target="_blank" href="http://parts.igem.org/Part:BBa_K185048">RelB</a><br/></td><td>++++</td><td>TA systems can stabilize plasmids and facilitate rapid adaptation of gut without negative effect on fitness of the human host<sup>[1]</sup>.</td> |
| </tr> | | </tr> |
| <tr> | | <tr> |
− | <td> Content A 2 </td> <td> Content B 2 这是igem hq的表格的写法。表格都需要说明,之前之后都会有p来文字 </td> | + | <td>Vital gene knock out</td><td>efficient</td><td>non-universal, time-consuming for testification.</td><td><a target="_blank" href="https://2019.igem.org/Team:NCKU_Tainan/Design"><i>can</i> gene knock out</a><br/><br/><a target="_blank" href="https://2019.igem.org/Team:Tuebingen/Killswitch">Deactivating Exendin-4 expression by Cas3</a></td><td>++++</td><td>Note 1</td> |
| </tr> | | </tr> |
| </table> | | </table> |
| + | <p>Note 1: The method of <i>can</i> gene knock out by 2019 Grand Prize winner is ingenious and effective. Unfortunately, it cannot be applied to our project. It has been reported that carbonic anhydrase, expression product of <i>can</i> gene, influence the release of PTH, leading to complex effects on bone remodeling. Carbonic anhydrase deficiency is manifested by osteopetrosis in human<sup>[2]</sup>. Although no concrete evidence has been found to show the relevance between carbonic anhydrase deficiency in intestinal microbiota and osteopetrosis, we decided to give up this method to avoid potential problems.</p> |
| | | |
− | <p></p><!-- 无文字p是换行隔开,在关闭的html元素间回车是没有用的 --> | + | <h6>Table 2. Summary of the mostly used Response system in intestinal probiotics project. (More “+” represents higher efficiency and more “-” represents stronger killing power.)</h6> |
− | | + | <table> |
− | <table class="striped"><!-- 这是另一个版本的表格,间隔行有阴影。一个页面不建议交叉两种格式。太宽表格可以加 responsive-table 方便窄屏 --> | + | |
| <tr> | | <tr> |
− | <th>Name</th> <th>Item Name</th> <th>Item Price</th> | + | <th>Physical Parameters</th> <th>Response System</th><th>Sensitivity</th><th>Killing power</th><th>Parts</th><th>Comments</th> |
| </tr> | | </tr> |
| <tr> | | <tr> |
− | <td>Alvin</td> <td>Eclair</td> <td>$0.87</td> | + | <td rowspan=3>Temperature (cold shock)</td> <td>Cold-acting promoter</td><td>++</td><td>---</td><td><a target="_blank" href="http://parts.igem.org/Part:BBa_K328001">PcspA</a></td><td>Working efficiently only below the room temperature (20℃).</td> |
| </tr> | | </tr> |
| <tr> | | <tr> |
− | <td>Alan</td> <td>Jellybean</td> <td>$3.76</td> | + | <td>cI repressor system</td><td>+++</td><td>---</td><td><a target="_blank" href=" http://parts.igem.org/Part:BBa_C0051">cI repressor</a><br/><br/><a target="_blank" href="http://parts.igem.org/Part:BBa_R0051">lambda cI regulated promoter</a><br/><br/><a target="_blank" href="http://parts.igem.org/Part:BBa_K2969022">TCI38</a><br/><br/><a target="_blank" href="http://parts.igem.org/Part:BBa_K2969021">TCI</a></td><td>Kill bacteria efficiently only when reaching 40℃, so it is not appropriate for our project that expect <i>E. coli</i> to survive at that temperature (fever). Moreover, it requires to express two types of proteins which imposes potential burden to the bacteria.</td> |
| </tr> | | </tr> |
| <tr> | | <tr> |
− | <td>Jonathan</td> <td>Lollipop</td> <td>$7.00</td> | + | <td>RNA thermometer</td> <td>+++++</td><td>----</td><td><a target="_blank" href="http://parts.igem.org/Part:BBa_K115002">FourU</a><br/><br/><a target="_blank" href="http://parts.igem.org/Part:BBa_K3247005">NoChill-06</a></td><td>Appropriate reaction temperature range, high sensitivity and high efficiency.</td> |
| + | </tr> |
| + | <tr><td rowspan=2>Concentration of essential nutrients in the intestine</td> <td>Glucose-sensitive promoter</td><td>++</td><td>---</td><td><a target="_blank" href="http://parts.igem.org/Part:BBa_K3036003">rpoH P5</a> <br/><br/><a target="_blank" href="http://parts.igem.org/Part:BBa_K3142012">PT-αCRP</a></td><td>Glucose starvation promoter PT-αCRP initiates transcription efficiently with concentration of glucose lower than 0.05%. The concentration of glucose in small intestine will reduce to 0.05% two hours after dinner and limit the survive of <i>E. coli</i>.</td> |
| + | </tr> |
| + | <tr> |
| + | <td>Fatty acid responsive repression system</td><td>+</td><td>--</td><td><a target="_blank" href="http://parts.igem.org/Part:BBa_K3096046">BBa_K3096046</a></td><td>Metabolites as responding factors, are greatly affected by food intake.</td> |
| + | </tr> |
| + | <tr><td rowspan=3>Other conditions</td> <td>N-Acetyl-Glucosamin-6 phosphate regulated repression system</td><td>+</td><td>--</td><td><a target="_blank" href="http://parts.igem.org/Part:BBa_K3096048">BBa_K3096048</a></td><td>It is not very efficient.</td> |
| + | </tr> |
| + | <tr> |
| + | <td>CO<sub>2</sub> concentration</td><td>++</td><td>----</td><td><a target="_blank" href="https://2019.igem.org/Team:NCKU_Tainan/Design"><i>can</i> gene knock out</a> </td><td>Note 1</td> |
| + | </tr> |
| + | <tr> |
| + | <td>Light condition</td> <td>+</td><td>-</td><td> <a target="_blank" href="https://2016.igem.org/Team:ShanghaiTechChina_B/Project#Kill_Switch">killer red</a> </td><td>Low efficiency and the demand of light illumination greatly limited its application contexts. |
| + | </td> |
| </tr> | | </tr> |
| </table> | | </table> |
| | | |
− | <p>Calciu 章节内分段 fety. tien China has an estimated 70 million osteoporosis patien China has an estimated 70 million osteoporosis patienChina has an estimated 70 million oste | + | <div class="column full_size"> |
− | oporosis patienChina has an estima
| + | <p>This summary will help future teams understand the killing effects and application scope of various Kill Switches. They could select the appropriate Kill Switch according to their own needs to achieve experimental safety.</p> |
− | ted 70 million osteoporosis pat tien China has an estimated 70 million osteoporosis patien China has an estimated 70 million osteoporosis patienChina has an estimated 70 million oste
| + | <p><br/>This contribution is mainly made by our team member Jingqi. You can enter our <a href="/Team:Fudan/Team#ZhangJQ">Team page</a> to learn more about her.</p> |
− | oporosis patienChina has an estimated 70 mill
| + | |
− | ion osteoporosis pattien China has an estimated 70 million osteoporosis patien China has an estimated 70 million osteoporosis patienChina has an estimated 70 million oste
| + | <div class="highlight decoration_B_full"> |
− | oporosis patienChina has an estimated 70 million osteoporosis pat
| + | <img src="https://static.igem.org/mediawiki/2020/a/ad/T--Fudan--contribution_004.png" alt="contribution of BBa_K3036004" /> |
− | </p>
| + | </div> |
| + | <br/> |
| + | <div class="highlight decoration_A_full"> |
| + | <img src="https://static.igem.org/mediawiki/2020/e/e7/T--Fudan--contribution_047.png" alt="contribution of BBa_K185047" /> |
| + | </div> |
| + | <br/> |
| + | <div class="highlight decoration_A_full"> |
| + | <img src="https://static.igem.org/mediawiki/2020/e/ef/T--Fudan--contribution_048.png" alt="contribution of BBa_K185048" /> |
| + | </div> |
| | | |
− | <p>From the us 章节内分段 etition.</p>
| |
| </div> | | </div> |
| + | <div class="clear"></div><!-- 一个章节结束需要clear来留白 --> |
| | | |
| + | <h2>Basic parts</h2> |
| + | <div class="column full_size"> |
| + | <p>Osteoporosis and other diseases caused by a calcium deficiency are common problems among the elderly in many regions such as China and India. We have discovered CaAP (Calcium Absorption Peptides), a class of oligopeptides that can chelate calcium and promote Caco-2 cells to uptake calcium, which can alleviate people's calcium deficiency problem, especially the elderly. This will provide help for the health care of the elderly in our area and is of good social value.</p> |
| + | <p>We learned from literature and designed the entire CaAP expression peptides sequence contains five different calcium-binding peptides, all of which have been proved through experiments to significantly increase calcium absorption <i>in vivo</i> or <i>in vitro</i>. Calcium ions spontaneously bind to the peptide's Asp or Glu residue, and calcium influx into intestinal epithelial cells is increased. The oligopeptide sequence is expressed as a complete peptide in the engineered bacteria and is cleaved into functional calcium absorption peptides in the presence of digestive enzymes in the intestinal lumen.</p> |
| + | <p>We have provided a new part <a href="http://parts.igem.org/Part:BBa_K3606000">CaAP</a> to the Registry. We obtained new information from the literature to support our project and provide new experimental data on the expression of CaAP in <i>E. coli</i> for future teams who will use the parts. You can read our <a href="/Team:Fudan/Experiments">Parts page</a> for specific information.</p> |
| + | |
| + | <p><br/>This contribution is mainly made by our team members Zhang Zhenru and Lu Yiyang. You can enter our <a href="/Team:Fudan/Team">Team page</a> to learn more about them.</p> |
| + | </div> |
| <div class="clear"></div><!-- 一个章节结束需要clear来留白 --> | | <div class="clear"></div><!-- 一个章节结束需要clear来留白 --> |
| | | |
− | <h2>再来例子 Market Analysis</h2> | + | <h2>Composite parts</h2> |
− | <div class="column half_size"> | + | <div class="column full_size"> |
− | <p>文本在左侧一半,宽屏 According to the Chinese Dietetic Sociietary Nutrient Intakes of Chinese Residents", the calcium requirement for infants and young children increases with age, from 300mg/day to 800mg/day, and the calcium requirement for adolescents reaches 1000mg/day. The amof the required intake, with the small exception of some coastal and pastoral areas 图片在右侧一半</p> | + | <p>We have noticed that the treatment of calcium deficiency is mainly aimed at the elderly. If we choose the treatment plan that patients take CaAP products regularly, they will likely forget to take the pills, and the efficacy will probably be unsatisfactory.</p> |
| + | <p>We learned from <a href="https://2019.igem.org/Team:Fudan/Design" target="_blank">19Fudan Team</a>, who had tried to make lactase controllable expressed in the intestine to treat lactose intolerance. We decided to establish a safe and controllable CaAP expression system using quorum sensing. The special promoter luxPR regulates the expression of CaAP. Under the regulation of our quorum-sensing system, bacteria's proliferation will be inhibited when they achieve the appropriate population, and CaAP expression begins. You can read our <a href="/Team:Fudan/Parts#Composite">Parts page</a> for detailed information.</p> |
| | | |
− | <table> | + | <p>This idea allows the engineered strains to act directly inside the human body, which is an effective way to replace the target substance synthesized <i>in vitro</i> and administered regularly. More importantly, it considers the elderly's difficulty. The commercialization of our project woould result in a market transformation and has efficient social significance.</p> |
− | <tr>
| + | <p>We improved the existing 19Fudan quorum sensing system. We increased the secretion of antimicrobial peptides by adopting a relatively low expression of antimicrobial peptides (mcbABCD) and high expression of the antimicrobial peptide immune portion (mcbEFG) from the reversed DNA strand. Those changes made our quorum system much more efficient and sensitive.</p> |
− | <th> 这是igem hq的表格的写法 </th> <th> Header 2 </th> <th> Header 3 </th> | + | <p><br/>This contribution was made by our team members Li Mingwei and Zhang Gaochen. You can go to our <a href="/Team:Fudan/Team">Team page</a> to learn more about them.</p> |
− | </tr> | + | |
− | <tr>
| + | <div class="highlight decoration_B_full"> |
− | <td> Content A 1 </td> <td> Content B 1 </td> <td> Content C 1 </td>
| + | <img src="https://static.igem.org/mediawiki/2020/7/7f/T--Fudan--contribution_029.png" alt="contribution of BBa_K3606029" /> |
− | </tr> | + | </div> |
− | <tr> | + | |
− | <td colspan=2> 列融合 </td> <td> Content C 2 这是igem hq的表格的写法。半幅或者2/3幅可以用。<br/>行融合<br/>就<br/>用br了 </td> | + | |
− | </tr>
| + | |
− | </table> | + | |
| | | |
| </div> | | </div> |
− | <div class="column half_size"> | + | <div class="clear"></div><!-- 一个章节结束需要clear来留白 --> |
− | <img src="https://static.igem.org/mediawiki/2020/0/00/T--Fudan--calcium_intake_graph.svg" alt="calcium intake graph">
| + | |
| + | |
| + | <h2>Improved part</h2> |
| + | <div class="column full_size"> |
| + | <div class="highlight decoration_B_full"> |
| + | <img src="https://static.igem.org/mediawiki/2020/5/5c/T--Fudan--conttibution_007.png" alt="contribution of BBa_K3606007" /> |
| + | </div> |
| + | <p>The part above has met Golden Medal criteria #2, which means we changed the sequences, and it improved an existing Part's function. We also did experiments with both the improved part and the original part as a control.</p> |
| </div> | | </div> |
| + | <div class="clear"></div><!-- 一个章节结束需要clear来留白 --> |
| | | |
− | <div class="clear extra_space"></div><!-- 一个章节结束需要clear来留白 因为马上最后一幅,建议extra_space --> | + | <h2>Parts collection</h2> |
| + | <div class="column full_size"> |
| + | <p>At the beginning of the experiment, we found that the circuit we designed could not operate successfully. We set out to construct a series of plasmids containing different parts for troubleshooting, hoping to assemble a complete circuit after removing the problems.</p> |
| + | <p>Our trouble shooting process provides a practical reference idea for any team who wants to study bacterial secreted proteins in the future. When they find that the complete circuit cannot work effectively, they can conduct experiments on individual parts separately, eliminate the fault, and finally re-assemble.</p> |
| + | <p>In result, we have provided a set of plasmids that these teams can use to solve their problems, which shows we are willing to put the idea of engineering and knowledge sharing into practice. You can read our <a href="/Team:Fudan/Part_Collection">Parts Collection</a> for detailed information.</p> |
| + | |
| + | <p><br/>This contribution was made by our team members Liu Yuanyuan, Lu Yiyang, Zhang Zhenru, Li Mingwei, and Zhang Gaochen. You can go our <a href="/Team:Fudan/Team">Team page</a>to learn more about our team members.</p> |
| + | </div> |
| + | |
| + | <div class="clear"></div><!-- 一个章节结束需要clear来留白 --> |
| + | |
| + | <h2>Measurement</h2> |
| | | |
| <div class="column full_size"> | | <div class="column full_size"> |
− | <p>每页结束需要小结,可以 ul ol 列表highlight,可以是每页第一段的另一种写法fety. tien China has an estimated 70 million osteoporosis patien China has an estimated 70 million osteoporosis patienChina has an estimated 70 million oste | + | <h4>Measure trace calcium on a test strip</h4> |
− | oporosis patienChina has an estima
| + | <p>Insufficient calcium intake or <u>excessive calcium supplementation</u> can cause a series of physical symptoms among the elderly. Therefore, it is necessary to provide convenient blood calcium testing for them. Routine blood calcium testing is cumbersome, so we try to improve the blood calcium detection method and provide the elderly with a simpler one that reduces drown blood volume. We hope they can conduct daily self-monitoring of their blood calcium status.</p> |
− | ted 70 million osteoporosis pat tien China has an estimated 70 million osteoporosis patien China has an estimated 70 million osteoporosis patienChina has an estimated 70 million oste
| + | <p>We have learned that the principle of measuring blood glucose through test strips. Glucose will generate red quinones with the effect of enzymes, which causes a change of absorbance. We can measure glucose concentration by detecting the intensity of light reflected by the test strips. The calcium ion in the serum can combine with methyl thymol blue and form a blue compound in an alkaline solution, which can also be determined by spectrophotometry. Therefore, we consider making test strips for measuring serum calcium ion concentration following the blood glucose measurement method. You can read our <a href="/Team:Fudan/Measurement">Measurement page</a> for more information.</p></div> |
− | oporosis patienChina has an estimated 70 mi 每页结束需要小结,可以 ul ol 列表highlight,可以是每页第一段的另一种写法</p>
| + | |
| + | <div class="column full_size"> |
| + | <h4>Hardware</h4> |
| + | <p>We also designed a supporting portable blood calcium meter with the simplest kinds of stuff, low-cost LED tubes and an existing mobile phone app. And we consider integrating blood calcium detection functions into existing blood glucose monitors. This kind of hardware has a simple structure and convenient operation, suitable for the elderly. Blood calcium can be detected with a small amount of blood sampling drown from fingers with a high detection sensitivity.</p> |
| + | <p>Our testing method helps discover <u>the problem of excessive calcium absorption</u> caused by probiotic activity, which can be easily solved by taking arabinose tablets in pharmacies (please read to our <a href="/Team:Fudan/Safety">Safety page</a>). It also provides users with reference data records of body calcium status. This is not only simple and clear in theory but also feasible in practical applications. We hope that the commercialization of our design can increase the attention to the elderly's health and promote social justice.</p> |
| + | <p><br/>This contribution was made by our team member Ziyuan. You can go to our <a href="/Team:Fudan/Team#WeiZY">Team page</a> to learn more about him.</p> |
| </div> | | </div> |
| + | |
| + | <div class="clear extra_space"></div><!-- 一个章节结束需要clear来留白 因为马上最后一幅,建议extra_space --> |
| + | |
| + | <div class="column full_size"> |
| + | <div class="highlight decoration_B_full"> |
| + | <h4>What we have done for the iGEM community:</h4> |
| + | <ul> |
| + | |
| + | <li><b>Education: </b>Popular biological science courses for the elderly</li> |
| + | <li><B>Human practice and entrepreneurship: </b>A complete business plan for transformation of scientific research results into commercial products</li> |
| + | <li><b>Modeling: </b>Improved modelings of the existing team to make it suitable for our project</li> |
| + | <li><b>Kill switch: </b>A more sensitive kill switch, ideal for the human body</li> |
| + | <li><b>Basic part and Composite part: </b>A kind of calcium absorbing peptides expressed in <i>E. coli</i> and excreted in the human intestine</li> |
| + | <li><b>Parts collection: </b>A series of plasmids for troubleshooting</li> |
| + | <li><b>Hardware: </b>A new method to detect blood calcium and a hardware intended for the elderly</li> |
| + | </ul> |
| + | </div></div> |
| + | |
| + | <div class="clear"></div><!-- 一个章节结束需要clear来留白 --> |
| | | |
| <div class="column full_size"><div id="FudanSignature"> | | <div class="column full_size"><div id="FudanSignature"> |
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− | style="margin-top:4rem" > | + | style="margin-top:4rem" tabIndex="0" > |
| <a href="http://www.yfc.cn/" target="_blank"><img class="col s3 m6 l4 FudanSponsors" alt="Yunfeng Capital" src="https://static.igem.org/mediawiki/2020/b/ba/T--Fudan--YFcapital.svg"> </a> | | <a href="http://www.yfc.cn/" target="_blank"><img class="col s3 m6 l4 FudanSponsors" alt="Yunfeng Capital" src="https://static.igem.org/mediawiki/2020/b/ba/T--Fudan--YFcapital.svg"> </a> |
| <a href="http://www.fudan.edu.cn/en/" target="_blank"><img alt="Fudan University" class="col s3 m6 l4 FudanSponsors" src="https://static.igem.org/mediawiki/2020/9/9d/T--Fudan--sponsor2.svg"> </a> | | <a href="http://www.fudan.edu.cn/en/" target="_blank"><img alt="Fudan University" class="col s3 m6 l4 FudanSponsors" src="https://static.igem.org/mediawiki/2020/9/9d/T--Fudan--sponsor2.svg"> </a> |
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− | <span><a href="/Team:Fudan/Description#Project">Project</a></span> | + | <span tabIndex="2"><a href="/Team:Fudan/Description#Project">Project</a></span> |
| <ul><li><a href="/Team:Fudan/Description">Description</a></li> | | <ul><li><a href="/Team:Fudan/Description">Description</a></li> |
| <li><a href="/Team:Fudan/Sustainable">Sustainable</a></li> | | <li><a href="/Team:Fudan/Sustainable">Sustainable</a></li> |
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− | <span><a href="/Team:Fudan/Notebook">Notebook</a></span> | + | <span tabIndex="3"><a href="/Team:Fudan/Notebook">Notebook</a></span> |
| <ul><li><a href="/Team:Fudan/Safety">Safety</a></li> | | <ul><li><a href="/Team:Fudan/Safety">Safety</a></li> |
| <li><a href="/Team:Fudan/Poster">Poster</a></li> | | <li><a href="/Team:Fudan/Poster">Poster</a></li> |
− | <li><a href="#">Video</a></li> | + | <li><a href="https://video.igem.org/videos/watch/7a0fee51-a637-4caf-aa97-a1d9bcafd3ba" target="_blank">Promotion</a></li> |
| + | <li><a href="#" target="_blank">Presentation</a></li> |
| + | <li><a href="/Team:Fudan/Entrepreneurship">Entrepreneurship</a></li> |
| </ul></div> | | </ul></div> |
| <div class="col s12 m4"> | | <div class="col s12 m4"> |
− | <span><a href="/Team:Fudan/Results">Results</a></span> | + | <span tabIndex="4"><a href="/Team:Fudan/Results">Results</a></span> |
| <ul><li><a href="/Team:Fudan/Contribution">Contribution</a></li><!-- replace Judging --> | | <ul><li><a href="/Team:Fudan/Contribution">Contribution</a></li><!-- replace Judging --> |
| + | <li><a href="/Team:Fudan/Implementation">Implementation</a></li> |
| <li><a href="/Team:Fudan/Engineering">Engineering</a></li> | | <li><a href="/Team:Fudan/Engineering">Engineering</a></li> |
| <li><a href="/Team:Fudan/Measurement">Measurement</a></li> | | <li><a href="/Team:Fudan/Measurement">Measurement</a></li> |
| <li><a href="/Team:Fudan/Model">Modeling</a></li> | | <li><a href="/Team:Fudan/Model">Modeling</a></li> |
− | <li><a href="/Team:Fudan/Entrepreneurship">Entrepreneurship</a></li>
| |
| </ul></div> | | </ul></div> |
| </div> | | </div> |
| <div class="col s12 l6 row"> | | <div class="col s12 l6 row"> |
| <div class="col s12 m4"> | | <div class="col s12 m4"> |
− | <span><a href="/Team:Fudan/Parts">Parts</a></span> | + | <span tabIndex="5"><a href="/Team:Fudan/Parts">Parts</a></span> |
| <ul><li><a href="/Team:Fudan/Parts#Basic">Basic part</a></li> | | <ul><li><a href="/Team:Fudan/Parts#Basic">Basic part</a></li> |
| <li><a href="/Team:Fudan/Parts#Composite">Composite part</a></li> | | <li><a href="/Team:Fudan/Parts#Composite">Composite part</a></li> |
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| </ul></div> | | </ul></div> |
| <div class="col s12 m4"> | | <div class="col s12 m4"> |
− | <span><a href="/Team:Fudan/Human_Practices">Outreach</a></span> | + | <span tabIndex="6"><a href="/Team:Fudan/Human_Practices">Outreach</a></span> |
| <ul><li><a href="/Team:Fudan/Human_Practices#Integrated">Integrated HP</a></li> | | <ul><li><a href="/Team:Fudan/Human_Practices#Integrated">Integrated HP</a></li> |
| <li><a href="/Team:Fudan/Education">Education</a></li> | | <li><a href="/Team:Fudan/Education">Education</a></li> |
Line 497: |
Line 517: |
| </ul></div> | | </ul></div> |
| <div class="col s12 m4"> | | <div class="col s12 m4"> |
− | <span><a href="/Team:Fudan/Team">Team</a></span> | + | <span tabIndex="7"><a href="/Team:Fudan/Team">Team</a></span> |
| <ul><li><a href="/Team:Fudan/Team">Members</a></li> | | <ul><li><a href="/Team:Fudan/Team">Members</a></li> |
| <li><a href="/Team:Fudan/Attributions">Attributions</a></li> | | <li><a href="/Team:Fudan/Attributions">Attributions</a></li> |
| <li><a href="/Team:Fudan/Partnership">Partnership</a></li> | | <li><a href="/Team:Fudan/Partnership">Partnership</a></li> |
| <li><a href="/Team:Fudan/Acknowledgement">Acknowledgement</a></li> | | <li><a href="/Team:Fudan/Acknowledgement">Acknowledgement</a></li> |
− | <li><a href="https://2019.igem.org/Team:Fudan-TSI/Heritage" target="_blank">Heritage</a></li> | + | <li><a href="/Team:Fudan/Heritage">Heritage</a></li> |
| </ul></div> | | </ul></div> |
| <div class="col s12 m4"> </div> | | <div class="col s12 m4"> </div> |