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− | <h1>Use Math to Explain and Simulate!</h1> | + | <h1 tabIndex="1">Simulate the Bacteria Quorum Sensing Process and Kill Switch</h1> |
| <div class="column full_size"> | | <div class="column full_size"> |
− | <p> | + | <p> |
| This year, we constructed two models to simulate the bacteria quorum sensing process and Kill Switch. For the quorum-sensing model, we used the Gillespie algorithm in random simulation to simulate the physiological processes at macro and micro levels. Specifically, we described Acyl-homoserine lactone's concentration accurately by monitoring both production and diffusion, which is first-of-its-kind to reveal details of the process, and developed originally by us. We further improved the model from 19Fudan team to better model the quorum sensing process for various bacteria growing stages. For the stage change caused by the anti-microbial peptide (mcbA), we provided explanations to its observed dynamic stability. For the Kill Switch model, based on the experimental data from 19BNU team, we improved the logistic equation, adjusted the promoter properties according to more suitable literature references, and made sensitivity analysis – and we obtain better and more insightful results. </p> | | This year, we constructed two models to simulate the bacteria quorum sensing process and Kill Switch. For the quorum-sensing model, we used the Gillespie algorithm in random simulation to simulate the physiological processes at macro and micro levels. Specifically, we described Acyl-homoserine lactone's concentration accurately by monitoring both production and diffusion, which is first-of-its-kind to reveal details of the process, and developed originally by us. We further improved the model from 19Fudan team to better model the quorum sensing process for various bacteria growing stages. For the stage change caused by the anti-microbial peptide (mcbA), we provided explanations to its observed dynamic stability. For the Kill Switch model, based on the experimental data from 19BNU team, we improved the logistic equation, adjusted the promoter properties according to more suitable literature references, and made sensitivity analysis – and we obtain better and more insightful results. </p> |
| </div> | | </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 --> | | <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>Model one:Bacteria Quorum Sensing Process</h2> | + | <h2>1. Bacteria Quorum Sensing Process</h2> |
− | | + | |
| <div class="column full_size"> | | <div class="column full_size"> |
− | <p>In the first model, we describe the quorum sensing process in three parts. In Model 1.1, we discuss the change of AHL concentration in a single cell. AHL is produced in bacteria and transported to the surrounding environment through free diffusion. Since the number of molecules in a single section is small and random, we adopted Gillespie algorithm to simulate the trend of molecule numbers under the random process. In model 1.2, we followed the discussion in 3.1. To know when the quorum sensing switch is turned on, it is necessary to know polymer concentration formed by AHL and LuxR when AHL concentration is high enough. Our results demonstrate that polymer concentration remains dynamically stable even in a single cell, which guarantees our system's stable operation. In Model 1.3, we discuss the role of antimicrobial peptide circuits. Since the loop will open when the concentration of AHL increases and will close when the concentration is low enough, it forms a dynamic equilibrium. We use a phase diagram to describe this steady state.</p> | + | <p> |
| + | In the first model, we describe the quorum sensing process in three parts. In Model 1.1, we discuss the change of AHL concentration in a single cell. AHL is produced in bacteria and transported to the surrounding environment through free diffusion. Since the number of molecules in a single section is small and random, we adopted Gillespie algorithm to simulate the trend of molecule numbers under the random process. In model 1.2, we followed the discussion in 1.1. To know when the quorum sensing switch is turned on, it is necessary to know polymer concentration formed by AHL and LuxR when AHL concentration is high enough. Our results demonstrate that polymer concentration remains dynamically stable even in a single cell, which guarantees our system's stable operation. In Model 1.3, we discuss the role of antimicrobial peptide circuits. Since the loop will open when the concentration of AHL increases and will close when the concentration is low enough, it forms a dynamic equilibrium. We use a phase diagram to describe this steady state.</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 --> |
| | | |
− | <h3>1.1 AHL in a cell</h3> | + | <h3>1.1 AHL in a Cell</h3> |
| + | <div class="column full_size"> |
| + | <p> |
| + | In this model, we simulate changes in the number of AHL in a cell. As mentioned above, AHL is generated inside the cell and transported out by free diffusion. In the initial stage, for AHL's concentration outside the bacteria is approximately 0, free diffusion is basically not inhibited and only related to AHL's concentration inside the cell. We believe that the main physiological processes about AHL are as follows. |
| + | </p> |
| + | <p> |
| + | <b>Gene expression</b>: the expression of AHL and LuxR: |
| + | </p> |
| + | </div> |
| | | |
− | $$
| + | <div class="row"> |
− | \phi \stackrel{\alpha_{con}}{\longrightarrow} LuxI\\
| + | <div class="col s2 m3 l4"> </div> |
− | \phi \stackrel{\alpha_{con}}{\longrightarrow} LuxR\\
| + | <div class="col s8 m6 l4"> |
− | Every Substance \stackrel{\mu}{\longrightarrow} \phi
| + | <img src="https://static.igem.org/mediawiki/2020/e/e2/T--Fudan--model1_1.png" alt="1_1" style="width:100%"> |
− | $$
| + | </div> |
| + | </div> |
| | | |
− | </div>
| + | <div class="column full_size"> |
− | <div class="clear"></div><!-- 一个章节结束需要clear来留白 -->
| + | <p> |
| + | <b>Protein degradation</b>: The degradation of AHL and LuxR: |
| + | </p></div> |
| | | |
− | <h2>每个章节标题用h2 为了搜索引擎全页面只能一个h1标签</h2> | + | <div class="row"> |
− | <div class="column third_size"> | + | <div class="col s2 m3 l4"> </div> |
− | <img src="https://static.igem.org/mediawiki/2020/8/8b/T--Fudan--map_2.svg" alt="map of calcium intake" /> | + | <div class="col s8 m6 l4"> |
− | </div>
| + | <img src="https://static.igem.org/mediawiki/2020/7/70/T--Fudan--model1_2.png" alt="1_2" style="width:100%"> |
− | <div class="column two_thirds_size">
| + | </div> |
− | <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 | + | </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> |
− | <p>However, for the Chinese population, the bottlenecks are
| + | <b>Changes about AHL</b>: The production of AHL and its diffusion outside the cell: |
− | as follows:
| + | </p> |
− | </p>
| + | </div> |
− | <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>
| + | |
| | | |
| + | <div class="row"> |
| + | <div class="col s2 m3 l4"> </div> |
| + | <div class="col s8 m6 l4"> |
| + | <img src="https://static.igem.org/mediawiki/2020/2/20/T--Fudan--model1_3.png" alt="1_3" style="width:100%"> |
| + | </div> |
| + | </div> |
| | | |
| + | <div class="column full_size"><p> |
| + | <b>Changes about RA</b>: The combination and dissociationof AHL and LuxR (noted as RA): |
| + | </p> |
| + | </div> |
| + | |
| + | <div class="row"> |
| + | <div class="col s2 m3 l4"> </div> |
| + | <div class="col s8 m6 l4"> |
| + | <img src="https://static.igem.org/mediawiki/2020/6/6c/T--Fudan--model1_4.png" alt="1_4" style="width:100%"> |
| + | </div> |
| + | </div> |
| + | |
| + | <div class="column full_size"> |
| <div class="highlight decoration_background decoration_A_top"> | | <div class="highlight decoration_background decoration_A_top"> |
− | <p>
| + | <center><h4>Gillespie Algorithm</h4></center> |
− | 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>The Gillespie algorithm is a mathematical method to simulate biochemical reactions with random processes. The main ideas of this algorithm are as follows:</p> |
| + | <p>(a) First, we divide the biochemical reaction process into several elemental reactions. The substances involved and their stoichiometric number are recorded in the form of a matrix.</p> |
| + | <p> |
| + | (b) Due to the rate constant and the concentration of reactants, the probability of different reactions is also different. We calculate the probability that each reaction will occur the next time. |
| + | </p> |
| + | <p> |
| + | (c) The knowledge of probability theory and stochastic processes tells us that the next reaction's time follows an exponential distribution, with the total reaction rate as its parameter. At that time, according to the possibility introduced in (b), a reaction occurs, causing a change in the number of molecules. |
| + | </p> |
| + | <p>By repeating the above process, we can simulate the random biochemical reactions within the system. |
| </p> | | </p> |
| </div> | | </div> |
− | <p>
| + | |
− | 章节内容的分段就用p开p关
| + | <p><br/> |
− | </p>
| + | In this matrix, each row is one substance, and each column is one reaction. The reactants per molecule are represented by -1, and the products per molecule are represented by 1. Set the order of the reactants to LuxI, LuxR AHLprecursor, AHL, RA, reaction sequence in the order listed above, then the matrix should be: |
− | <div class="highlight decoration_B_full"> | + | </p> |
| + | </div> |
| + | |
| + | <div class="row"> |
| + | <div class="col s2 m3 l4"> </div> |
| + | <div class="col s8 m6 l4"> |
| + | <img src="https://static.igem.org/mediawiki/2020/2/23/T--Fudan--model1_5.png" alt="1_5" style="width:100%"> |
| + | </div> |
| + | </div> |
| + | |
| + | <div class="column full_size"><p> |
| + | After each reaction, the number of molecules changes by the number of a column. What column is that? The probability is proportional to the rate of reaction. So let's figure out the rates of all the reactions. |
| + | </p> |
| + | </div> |
| + | |
| + | <div class="row"> |
| + | <div class="col s2 m3 l4"> </div> |
| + | <div class="col s8 m6 l4"> |
| + | <img src="https://static.igem.org/mediawiki/2020/4/4b/T--Fudan--model1_6.png" alt="1_6" style="width:100%"> |
| + | </div> |
| + | </div> |
| + | |
| + | <div class="column full_size"><p> |
| + | So the probability is as follows: |
| + | </p> |
| + | </div> |
| + | |
| + | <div class="row"> |
| + | <div class="col s2 m3 l4"> </div> |
| + | <div class="col s8 m6 l4"> |
| + | <img src="https://static.igem.org/mediawiki/2020/1/1b/T--Fudan--model1_7.png" alt="1_7" style="width:100%"> |
| + | </div> |
| + | </div> |
| + | <div class="row"> |
| + | <div class="col s2 m3 l4"> </div> |
| + | <div class="col s8 m6 l4"> |
| + | <img src="https://static.igem.org/mediawiki/2020/e/e5/T--Fudan--model1_8.png" alt="1_8" style="width:100%"> |
| + | </div> |
| + | </div> |
| + | |
| + | <div class="column full_size"><p> |
| + | According to probability theory, the time interval between each reaction follows the exponential distribution, and the parameter is the sum rate. |
| + | </p> |
| + | <p> |
| + | The current molecule number will change after each reaction, so that this algorithm can be repeated.In this certain progress,we can see that AHL molecule number is changed as follows (We provide 2 simulated results to gain better understanding): |
| + | </p></div> |
| + | |
| + | <div class="column half_size"><p> |
| + | <img src="https://static.igem.org/mediawiki/2020/b/b0/T--Fudan--model1_9.png" alt="1_9" /> |
| + | </p></div> |
| + | <div class="column half_size"><p> |
| + | <img src="https://static.igem.org/mediawiki/2020/5/56/T--Fudan--model1_10.png" alt="1_10" /> |
| + | </p></div> |
| + | |
| + | <div class="column full_size"> |
| + | <div class="highlight decoration_background decoration_B_full"> |
| <p> | | <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
| + | The result shows that at the early stage of colonization, AHL will be rapidly produced and diffused to a high concentration, leading to the generation of RA and the initiation of quorum sensing. |
| </p> | | </p> |
| </div> | | </div> |
− | <p>
| + | <p> |
− | 章节内容的分段就用p开p关
| + | Noted: this is just AHL in a single cell. We should keep in mind that <i>E. coli</i> also completes the colonization process at the same time. |
− | </p>
| + | </p> |
− | <p>
| + | </div> |
− | 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>
| + | |
− | </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 -->
| + | |
| | | |
− | <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 -->
| + | <div class="clear"></div><!-- 一个章节结束需要clear来留白 --> |
| + | |
| + | <h3>1.2 RA (LuxR-AHL), the Switch</h3> |
| | | |
− | <h2>又来个章节 sis</h2>
| |
| <div class="column full_size"> | | <div class="column full_size"> |
− | <p>引入文字 ion.</p>
| + | <p>In the previous model, we have discussed the rapid emergence and spread of AHL during breeding. When the concentration of AHL is high enough, the net diffusion rate can be almost zero. At this point, the intracellular reaction occurs that is identical to model 1.1 except for diffusion. Therefore, we used the same simulation method and considered the situation before the secretion of antimicrobial peptides. We obtain the changes of RA in a cell number. Since the process is still random, we provide the results of two simulations.</p> |
− | <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>
| + | </div> |
| + | |
| + | <div class="column half_size"><p> |
| + | <img src="https://static.igem.org/mediawiki/2020/d/d3/T--Fudan--model1_11.png" alt="1_11" /> |
| + | </p></div> |
| + | <div class="column half_size"><p> |
| + | <img src="https://static.igem.org/mediawiki/2020/a/ac/T--Fudan--model1_12.png" alt="1_12" /> |
| + | </p></div> |
| + | |
| + | <div class="column full_size"> |
| + | <div class="highlight decoration_background decoration_B_full"><p> |
| + | As you can see, although the number of molecules varies, it ends up being relatively stable. This proves that our system has a self-steady state regulating quorum sensing state. |
| + | </p> |
| + | </div></div> |
| + | |
| + | <div class="clear"></div><!-- 一个章节结束需要clear来留白 --> |
| + | |
| + | <h3>1.3 Engineering Bacteria Number Circulation</h3> |
| + | <div class="column full_size"> |
| + | <p> |
| + | As the quorum sensing switch is turned on, the antimicrobial peptides begin to kill engineering bacteria, and the number of engineering bacteria decreases. Subsequently, the concentration of AHL decreases, resulting in a decrease in RA concentration and a partial shutdown of the quorum sensing switch. Our system ensures that engineering bacteria are neither too many to affect the gut environment nor too few to function properly. We will describe this process in terms of differential equations and explain it in terms of phase diagrams. |
| + | </p> |
| + | <p> |
| + | For AHL, the increase in the number of engineered bacteria will slow down the net degradation rate of AHL, which can be described as follows: |
| + | </p> |
| + | </div> |
| + | |
| + | <div class="row"> |
| + | <div class="col s2 m3 l4"> </div> |
| + | <div class="col s8 m6 l4"> |
| + | <img src="https://static.igem.org/mediawiki/2020/5/54/T--Fudan--model1_13.png" alt="1_13" style="width:100%"> |
| + | </div> |
| + | </div> |
| + | |
| + | <div class="column full_size"><p> |
| + | As for engineering bacteria, there is a net growth under no other conditions. However, the increase in AHL concentration will eventually lead to a rise in antimicrobial peptides. Furthermore, antimicrobial peptides will increase the survival pressure of engineering bacteria. So we can describe the process as follows: |
| + | </p> |
| + | </div> |
| + | |
| + | <div class="row"> |
| + | <div class="col s2 m3 l4"> </div> |
| + | <div class="col s8 m6 l4"> |
| + | <img src="https://static.igem.org/mediawiki/2020/1/16/T--Fudan--model1_14.png" alt="1_14" style="width:100%"> |
| + | </div> |
| + | </div> |
| + | |
| + | <div class="column full_size"><p> |
| + | We set k<sub>A-N</sub>to 1, and obtain the following two results.The first is a phase diagram and the second is a concentration-time diagram. |
| + | </p></div> |
| + | |
| + | <div class="column half_size"><p> |
| + | <img src="https://static.igem.org/mediawiki/2020/b/b6/T--Fudan--model1_15.png" alt="1_15" /> |
| + | </p></div> |
| + | <div class="column half_size"><p> |
| + | <img src="https://static.igem.org/mediawiki/2020/0/02/T--Fudan--model1_16.png" alt="1_16" /> |
| + | </p></div> |
| + | |
| + | <div class="column full_size"> |
| + | <div class="highlight decoration_background decoration_B_full"><p> |
| + | From the two phases, we see our system can operate dynamically. |
| + | </p> |
| + | <p> |
| + | From the second phase, we can see that the phase change of AHL lags behind the number of engineering bacteria. This tells us that the concentration of AHL has a time-delay effect, which is the essential reason why the system remains steady. |
| + | </p> |
| + | </div></div> |
| + | |
| + | <div class="clear extra_space"></div><!-- 一个章节结束需要clear来留白 --> |
| + | |
| + | <h2 id="killswitch">2. Kill Switch</h2> |
| + | <div class="column full_size"><p> |
| + | In the modeling of kill Switch, we adopted the following ideas: First, we cooperated with the 19BNU team and adopted the data they tested. We found that without kill-switch, the colony number curve was similar to the logistic equation. Through data fitting, we obtained the parameters of the logistic equation. When kill-switch exists, <i>in vitro</i>, the toxin will increase the competitive pressure, causing parameters' change. Due to the improvement of a more efficient promoter, the competitive pressure caused by toxin can further increase when our design is adopted, and we performed sensitivity analysis here. Due to the abnormal part of the experimental data, we also selected the experimental data by referring to the literature and will explain the reasons for these anomalies. |
| + | </p></div> |
| + | |
| + | <div class="clear"></div><!-- 一个章节结束需要clear来留白 --> |
| + | |
| + | <h3>2.1 Logistic Equation</h3> |
| + | <div class="column full_size"><p> |
| + | Let's discuss logistic equation first. In this equation,the population change is caused by two factors: reproduction and competition. The reproductive rate (r) is proportional to the number of bacteria,and the competition rate (K) is proportional to the number of bacteria in the quadratic term. The equation and its solution are as follows. |
| + | </p> |
| + | </div> |
| + | |
| + | <div class="row"> |
| + | <div class="col s2 m3 l4"> </div> |
| + | <div class="col s8 m6 l4"> |
| + | <img src="https://static.igem.org/mediawiki/2020/6/64/T--Fudan--model2_2.png" alt="2_2" style="width:100%"> |
| + | </div> |
| + | </div> |
| + | |
| + | <div class="clear"></div> |
| + | |
| + | <h3>2.2 Control Group</h3> |
| + | <div class="column full_size"><p> |
| + | We can fairly consider that density in control group fits logistic equation. We fit the experimental data as follows. |
| + | </p> |
| + | </div> |
| + | |
| + | <div class="row"> |
| + | <div class="col m2 l3 hide-on-small-only"> </div> |
| + | <div class="col s12 m8 l6"> |
| + | <img src="https://static.igem.org/mediawiki/2020/b/b6/T--Fudan--model2_1.png" alt="2_1" style="width:100%"> |
| + | </div> |
| + | </div> |
| + | |
| + | <div class="clear"></div> |
| + | |
| + | <h3>2.3 Experiment Group and Improvement</h3> |
| + | <div class="column full_size"><p> |
| + | Now let's consider the case when kill-switch is turned on.Competitive pressure sharply increases,casing a change in the equation above, in which α indicates additional pressure. |
| + | </p> |
| + | </div> |
| + | |
| + | <div class="row"> |
| + | <div class="col s2 m3 l4"> </div> |
| + | <div class="col s8 m6 l4"> |
| + | <img src="https://static.igem.org/mediawiki/2020/0/00/T--Fudan--model2_3.png" alt="2_3" style="width:100%"> |
| + | </div> |
| + | </div> |
| + | |
| + | <div class="column full_size"><p> |
| + | Furthermore, with an improvement in RNA thermometer, the toxin/antitoxin system express better in our design.Consider the expression partition k<sub>new</sub> and k<sub>old</sub>.The equation of our system will be: |
| + | </p> |
| + | </div> |
| + | |
| + | <div class="row"> |
| + | <div class="col s2 m3 l4"> </div> |
| + | <div class="col s8 m6 l4"> |
| + | <img src="https://static.igem.org/mediawiki/2020/5/54/T--Fudan--model2_4.png" alt="2_4" style="width:100%"> |
| + | </div> |
| + | </div> |
| + | <div class="column full_size"> |
| + | <p><br/><br/>However, when looking at experiment data, we see some abnormal increase throughout time. Here are some possible reasons. |
| + | </p> |
| <ol> | | <ol> |
− | <li>The produc</li> | + | <li>Toxin-antitoxin plasmid lost nts</li> |
− | <li>The short pep</li> | + | <li>The cellular repair mechanism</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>Cell detoxification</li> |
− | <li>There is a kill swit.</li>
| + | |
− | </ol>
| + | |
| | | |
− | <p> | + | </ol></div> |
− | 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
| + | <div class="column full_size"><p>So we only use earlier experiment data in fitting. Wevisualize the results of former and improved kill-switch here.</p></div> |
− | 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
| |
− | 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>
| |
| | | |
− | <table> | + | |
| + | <div class="row"> |
| + | <div class="col m2 l3 hide-on-small-only"> </div> |
| + | <div class="col s12 m8 l6"> |
| + | <img src="https://static.igem.org/mediawiki/2020/2/25/T--Fudan--model2_6.png" alt="2_6" style="width:100%"> |
| + | </div> |
| + | </div> |
| + | |
| + | <div class="column full_size"> |
| + | <div class="highlight decoration_background decoration_B_full"> |
| + | <p>The result shows that our Kill Switch reacts stronger in a smaller temperature range. It's clear that our improvement did a good job, thus improve the safety. </p> |
| + | <p>We conducted a further sensitivity analysis, finding that RNA thermometer expression level has a continuous and stable impact on the killing rate.</p> |
| + | </div></div> |
| + | |
| + | |
| + | <div class="clear"></div><!-- 一个章节结束需要clear来留白 --> |
| + | |
| + | <h2>Modeling and Our Project</h2> |
| + | <div class="column full_size"><p> |
| + | Our models do an excellent job of filling in the gaps when were challenging to implement. Firstly, since web-lab experiments cannot be carried out until recently, our model simulates the change of the number of molecules in the engineering bacteria and the process of quorum sensing. Furthermore, we prove that it is feasible to realize the dynamic balance of engineering bacteria quantity through quorum sensing in project design. Our design excellence in the Kill-Switch model is demonstrated by visualizing a better kill rate caused by RNA Thermometer parameters change. As a result, our model fits in well with the project. |
| + | </p></div> |
| + | |
| + | <div class="column full_size"> |
| + | <h4>Parameters Used for Simulation and Regression</h4> |
| + | <table class="striped"> |
| <tr> | | <tr> |
− | <th> Header 1 这是igem hq的表格的写法 </th> <th> Header 2 </th> | + | <th> Signal </th> <th> Meaning </th> <th> Value. </th> |
| </tr> | | </tr> |
| <tr> | | <tr> |
− | <td> Content A 1 </td> <td> Content B 1 </td> | + | <td> α<sub>con</sub> </td> <td> Gene production rate </td> <td> 0.0167 nM/s </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> μ </td> <td> Degradation rate </td> <td> 0.0038 /s </td> |
| </tr> | | </tr> |
− | </table>
| |
− |
| |
− | <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 -->
| |
− |
| |
− | <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> | + | <td> α<sub>AHL</sub> </td> <td> AHL production rate </td> <td> 0.167 nM/s </td> |
| </tr> | | </tr> |
| <tr> | | <tr> |
− | <td>Alvin</td> <td>Eclair</td> <td>$0.87</td> | + | <td> k<sub>on</sub> </td> <td> AHL and LuxR combination rate </td> <td> 0.03 nM-1/s </td> |
| </tr> | | </tr> |
| <tr> | | <tr> |
− | <td>Alan</td> <td>Jellybean</td> <td>$3.76</td> | + | <td> k<sub>off</sub> </td> <td> RA disposition rate </td> <td> 0.167 nM/s </td> |
| </tr> | | </tr> |
| <tr> | | <tr> |
− | <td>Jonathan</td> <td>Lollipop</td> <td>$7.00</td> | + | <td> k<sub>dif</sub> </td> <td> AHL transfer rate between invitro and invivio </td> <td> 1.83 /s </td> |
| </tr> | | </tr> |
− | </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
| |
− | oporosis patienChina has an estima
| |
− | 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
| |
− | 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
| |
− | oporosis patienChina has an estimated 70 million osteoporosis pat
| |
− | </p>
| |
− |
| |
− | <p>From the us 章节内分段 etition.</p>
| |
− | </div>
| |
− |
| |
− | <div class="clear"></div><!-- 一个章节结束需要clear来留白 -->
| |
− |
| |
− | <h2>再来例子 Market Analysis</h2>
| |
− | <div class="column half_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>
| |
− |
| |
− | <table>
| |
| <tr> | | <tr> |
− | <th> 这是igem hq的表格的写法 </th> <th> Header 2 </th> <th> Header 3 </th> | + | <td> r </td> <td> Bacteria growth rate </td> <td> 0.079 /s </td> |
| </tr> | | </tr> |
| <tr> | | <tr> |
− | <td> Content A 1 </td> <td> Content B 1 </td> <td> Content C 1 </td> | + | <td> K </td> <td> Bacteria competition rate </td> <td> 1.663e-04 /s </td> |
| </tr> | | </tr> |
| <tr> | | <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> | + | <td> α </td> <td> Additional competition rate </td> <td> 1.013 /s </td> |
| </tr> | | </tr> |
− | </table> | + | <tr> |
| + | <td> k<sub>A-N</sub> </td> <td> Bacteria density decrease caused by AHL </td> <td> 1 /s </td> |
| + | </tr> |
| + | <tr> |
| + | <td> k<sub>new</sub> </td> <td> New RNA thermometer expression rate </td> <td> 0.102360391 </td> |
| + | </tr> |
| + | <tr> |
| + | <td> k<sub>old</sub> </td> <td> Old RNA thermometer expression rate </td> <td> 0.394639 </td> |
| + | </tr> |
| + | </table></div> |
| | | |
− | </div>
| + | <div class="column full_size"> |
− | <div class="column half_size">
| + | <p><a target="_blank" href="https://static.igem.org/mediawiki/2020/c/ca/T--Fudan--data_from_19BNU.xlsx">Data provied by 19BNU-China</a></p></div> |
− | <img src="https://static.igem.org/mediawiki/2020/0/00/T--Fudan--calcium_intake_graph.svg" alt="calcium intake graph">
| + | |
− | </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"> |
| + | <h4>Reference</h4> |
| + | <p> |
| + | [1] Melke, P., et al., A cell-based model for quorum sensing in heterogeneous bacterial colonies. PLoS Comput Biol, 2010. 6(6): p. e1000819.</p> |
| + | <p>[2] A.B.Goryachev,D.J.TohT.Lee, Systems analysis of a quorum sensing network: Design constraints imposed by the functional requirements, network topology and kinetic constants. Biosystems,Volume 83, Issues 2–3, February–March 2006, Pages 178-187</p> |
| + | <p>[3] <a href="https://2019.igem.org/Team:Fudan/Model">https://2019.igem.org/Team:Fudan/Model</a></p> |
| + | <p>[4] Darren J. Wilkinson, Stochastic Modelling for Systems Biology.</p> |
| + | <p>[5] Martin Overgaard, Jonas Borch, and Kenn Gerdes, RelB and RelE of <i>Escherichia coli</i> Form a Tight Complex That Represses Transcription via the Ribbon–Helix–Helix Motif in RelB. J Mol Biol. 2009 Nov 27; 394(2): 183–196.</p> |
| + | <p>[6] <a href="http://parts.igem.org/Part:BBa_K3247005">http://parts.igem.org/Part:BBa_K3247005</a></p> |
| + | <p>[7] <a href="http://parts.igem.org/Part:BBa_K115002">http://parts.igem.org/Part:BBa_K115002</a></p> |
| + | </div> |
| | | |
− | <div class="column full_size">
| + | <div class="column full_size"><p style="text-align:center"> |
− | <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
| + | See our codes at <a href="https://github.com/Isabel-Jiang/2020-model" target="_blank">https://github.com/Isabel-Jiang/2020-model</a>! |
− | oporosis patienChina has an estima
| + | </p></div> |
− | 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
| + | |
− | 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="clear"></div> |
− | </div>
| + | |
| + | <div class="column full_size"><div id="FudanSignature"> |
| + | <p>Signature: <a href="/Team:Fudan/Attributions#JiangXH" class="z-depth-2">Xiaohui</a> |
| + | </p> |
| + | </div></div> |
| | | |
− | <div class="column full_size"><div id="FudanSignature">
| |
− | <p>Signature: <a href="/Team:Fudan/Attributions#JiangXH" class="z-depth-2">Xiaohui</a>
| |
− | </p>
| |
− | </div></div>
| |
| | | |
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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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| <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> |
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| <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><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> |
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| <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> |