text

static/model.md

+# Modelling
+
+## Introduction
+
+Mathematical modeling serves as a crucial tool for analyzing the feasibility of our project. In the design of our products, we aim to compare the effectiveness of two strategies: the expression of PAL under the T7 and TCA (trans-cinnamic acid) promoters with the amplification switch of TP901, and to test the degree of influence of environmental TCA concentration on the inversion efficiency of TP901 integrase. In this section, we employ ordinary differential equations (ODEs) to describe the degradation process of Phe (phenylalanine), then made numerical simulations using MATLAB. This approach allows us to delve into the intricate dynamics of our biological system and make informed decisions for our iGEM project.
+
+To describe the kinetic characteristics of the degradation system, we first describe the transcription, translation, T7 promoter inversion, and Phe degradation process within a single bacterium. For the transcription activated by the TCA promoter, we use the Hill equation to represent the influence of TCA concentration on the transcription rate. For the inversion of the T7 promoter and the degradation of Phe, since both are enzyme-catalyzed reactions, we use the Michaelis-Menten equation. After modeling a single bacterium, to represent the interaction between bacteria and the environment, we use a diffusion model to describe the concentrations of Phe and TCA inside and outside the bacteria, and use a Logistic model to describe the number of bacteria.
+
+## Dynamic models
+
+### TCA promoter
+
+For the promoter activated by TCA, it is assumed that the promoter can promote transcription after binding with TCA. According to Hill kinetics equations, the proportion of TCA promoter activation $\theta$ and the relationship with the concentration of TCA in bacteria $[TCA_{in}]$ can be described by
+
+$$
+\theta=\frac{[TCA_{in}]^n}{K_d+[TCA_{in}]^n},
+$$
+
+where $n$ is the Hill coefficient, which can be regarded as 1 when allosteric effects are not considered, and $K_d$ is the dissociation equilibrium constant for the binding-dissociation reaction. Experiments show that in the absence of TCA, the TCA promoter can also be transcribed slowly. Therefore, the transcription rate of the TCA promoter can be represented by 
+
+$$
+v_{trans}=\alpha_1 + \beta\theta(1+g)=\alpha_1+\frac{\beta(1+g)[TCA_{in}]}{K_d+[TCA_{in}]},
+$$
+
+where $\alpha_1$ is the transcription rate when the promoter is not activated, $\beta$ is the increment of the transcription rate after the promoter is activated, and $g$ is the gain of hcaE’ to the transcription rate. Considering the spontaneous degradation of mRNA, the change rate of the concentration of mRNA1 used to translate TP901 can be represented as
+
+$$
+\frac{d[mRNA_1]}{dt}=\alpha_1+\frac{\beta(1+g)[TCA_{in}]}{K_d+[TCA_{in}]}-\delta_1[mRNA_1],
+$$
+
+where $\delta_1$ is the spontaneous degradation rate of this mRNA.
+
+### Translation
+
+The translation rate is positively related to the concentration of mRNA, and for the translation of TP901 and PAL, since they use the same RBS, their synthesis rates can be approximated regareded as the same, that is
+
+$$
+\begin{aligned}
+\frac{d[TP901]}{dt}&=\alpha_3[mRNA_1]-\delta_3[TP901], \\
+\frac{d[PAL]}{dt}&=\alpha_3[mRNA_2]-\delta_4[PAL], \\
+\end{aligned}
+$$
+
+where $[mRNA_2]$ is the concentration of mRNA which is used to translate PAL.
+
+### Inversion of T7 promoter
+
+Assuming that the inversion of the promoter is an irreversible enzyme-catalyzed reaction, if the proportion of inverted promoters is denoted as $\eta$, then the rate of change of $\eta$ satisfies the Michaelis-Menten equation, that is
+
+$$
+\frac{d\eta}{dt}=\frac{v_{m,1}[TP901](1-\eta)}{K_{m,1}+1-\eta},
+$$
+
+where $v_{m,1}$ is the maximum rate of the inversion reaction, and $K_{m,1}$ is the Michaelis constant for this reaction. Since only the successfully inverted promoters can participate in transcription, the change in $[mRNA_2]$ can be represented by
+
+$$
+\frac{d[mRNA_2]}{dt}=\alpha_2\eta-\delta_1[mRNA_2],
+$$
+
+where the spontaneous degradation rate of this mRNA is also $\delta_1$ as the rate for mRNA with different sequences are approximately the same.
+
+### Degradation of Phe
+
+Inside the bacteria, the reaction of Phe degrading into TCA can be described by the Michaelis-Menten equation, that is
+
+$$
+\begin{aligned}
+\frac{d[TCA_{in}]}{dt}\bigg|_{reaction}& = \frac{v_{m,2}[PAL][Phe_{in}]}{K_{m,2}+[Phe_{in}]}, \\
+\frac{d[Phe_{in}]}{dt}\bigg|_{reaction}& = -\frac{v_{m,2}[PAL][Phe_{in}]}{K_{m,2}+[Phe_{in}]}, \\
+\end{aligned}
+$$
+
+where $[Phe_{in}]$ represents the concentration of Phe in the bacteria.
+
+### Transport of Phe and TCA
+
+Since the transport of Phe and TCA are both transmembrane transport, if the concentrations of Phe and TCA outside the bacteria are denoted as $[Phe_{out}]$ and $[TCA_{out}]$ respectively, then according to Fick's first law, we have
+
+$$
+\begin{aligned}
+\frac{d[Phe_{in}]}{dt}\bigg|_{diffusion}&=\gamma_1([Phe_{out}]-[Phe_{in}]), \\
+\frac{d[Phe_{out}]}{dt}\bigg|_{diffusion}&=-\lambda N\gamma_1([Phe_{out}]-[Phe_{in}]), \\
+\frac{d[TCA_{in}]}{dt}\bigg|_{diffusion}&=\gamma_2([TCA_{out}]-[TCA_{in}]), \\
+\frac{d[TCA_{out}]}{dt}\bigg|_{diffusion}&=-\lambda N\gamma_2([TCA_{out}]-[TCA_{in}]),
+\end{aligned}
+$$
+
+where $\gamma_1$ and $\gamma_2$ are the transmembrane diffusion rates of Phe and TCA respectively, $N$ is the number of bacteria, and $\lambda$ is a coefficient that approximates the ratio of the volume of the bacteria to the volume of the solution. Based on this, we can combine the above equations to get the equations below.
+
+$$
+\begin{aligned}
+\frac{d[Phe_{in}]}{dt}&=\gamma_1([Phe_{out}]-[Phe_{in}])-\frac{v_{m,2}[PAL][Phe_{in}]}{K_{m,2}+[Phe_{in}]}, \\
+\frac{d[Phe_{out}]}{dt}&=-\lambda N\gamma_1([Phe_{out}]-[Phe_{in}]), \\
+\frac{d[TCA_{in}]}{dt}&=\gamma_2([TCA_{out}]-[TCA_{in}])+\frac{v_{m,2}[PAL][Phe_{in}]}{K_{m,2}+[Phe_{in}]}, \\
+\frac{d[TCA_{out}]}{dt}&=-\lambda N\gamma_2([TCA_{out}]-[TCA_{in}]).
+\end{aligned}
+$$
+
+### Growth of bacteria
+
+Logistic model can be used to simulate the growth of bacteria. That is, if the growth rate of bacteria without other bacterial inhibition is $r$, and the environmental carrying capacity is $N_m$, then the growth rate of bacterias is:
+
+$$
+\frac{dN}{dt}=rN\left(1-\frac{N}{N_{m}}\right).
+$$
+
+### Summary
+
+By summarizing the above results and assuming that all molecular concentrations inside all bacteria are the same, we obtain that the entire process satisfies the following differential equations:
+
+$$
+\begin{aligned}
+\frac{d[mRNA_1]}{dt}&=\alpha_1+\frac{\beta(1+g)[TCA_{in}]}{K_d+[TCA_{in}]}-\delta_1[mRNA_1], \\
+\frac{d[mRNA_2]}{dt}&=\alpha_2\eta-\delta_1[mRNA_2], \\
+\frac{d[TP901]}{dt}&=\alpha_3[mRNA_1]-\delta_3[TP901], \\
+\frac{d[PAL]}{dt}&=\alpha_3[mRNA_2]-\delta_4[PAL], \\
+\frac{d\eta}{dt}&=\frac{v_{m,1}[TP901](1-\eta)}{K_{m,1}+1-\eta}, \\
+\frac{d[Phe_{in}]}{dt}&=\gamma_1([Phe_{out}]-[Phe_{in}])-\frac{v_{m,2}[PAL][Phe_{in}]}{K_{m,2}+[Phe_{in}]}, \\
+\frac{d[Phe_{out}]}{dt}&=-\lambda N\gamma_1([Phe_{out}]-[Phe_{in}]), \\
+\frac{d[TCA_{in}]}{dt}&=\gamma_2([TCA_{out}]-[TCA_{in}])+\frac{v_{m,2}[PAL][Phe_{in}]}{K_{m,2}+[Phe_{in}]}, \\
+\frac{d[TCA_{out}]}{dt}&=-\lambda N\gamma_2([TCA_{out}]-[TCA_{in}]), \\
+\frac{dN}{dt}&=rN\left(1-\frac{N}{N_{m}}\right).
+\end{aligned}
+$$
+
+## Numerical simulation
+
+In order to compare the performance of T901-T7 promoter coupled system and TCA promoter system in different initial TCA concentration, we simulate via MATLAB. Initial values of variables, values of constants, and simulation result are shown below.
+
+#### Table 1: Variable list
+
+| Variable      | Meaning                                                  | Unit   | Initial Value |
+| ------------- | -------------------------------------------------------- | ------ | ------------- |
+| $[TCA_{in}]$  | Concentration of trans-cinnamic acid inside of bacteria  | mM     | 0             |
+| $[TCA_{out}]$ | Concentration of trans-cinnamic acid outside of bacteria | mM     | 0 or 1        |
+| $[Phe_{in}]$  | Concentration of phenylalanine inside of bacteria        | mM     | 0             |
+| $[Phe_{out}]$ | Concentration of phenylalanine outside of bacteria       | mM     | 1             |
+| $[mRNA_1]$    | Concentration of mRNA used to translate TP901            | nM     | 0             |
+| $[mRNA_2]$    | Concentration of mRNA used to translate PAL              | nM     | 0             |
+| $[TP901]$     | Concentration of integrase TP901                         | $\mu$M | 0             |
+| $[PAL]$       | Concentration of phenylalanine ammonia-lyase             | $\mu$M | 0             |
+| $\eta$        | Ratio of inversed T7 promoter                            | None   | 0             |
+| $N$           | Number of bacteria                                       | None   | $10^8$        |
+
+#### Table 2: Parameter list
+
+| Parameter  | Meaning                                                      | Unit                  | Value      |
+| ---------- | ------------------------------------------------------------ | --------------------- | ---------- |
+| $K_d$      | Dissociation equilibrium constant for the binding-dissociation reaction of TCA to PTCA | mM                    | 0.5        |
+| $\beta$    | Increment of the transcription rate after the promoter is activated | min$^{-1}$            | 0.5        |
+| $g$        | Gain of hcaE’ to the transcription rate                      | None                  | 1          |
+| $\alpha_1$ | Transcription rate of mRNA1 when the TCA promoter is not activated | nM/min                | 0.01       |
+| $\alpha_2$ | Transcription rate of mRNA2                                  | nM/min                | 2.5        |
+| $\alpha_3$ | Translation rate                                             | $\mu$M/(nM$\cdot$min) | 0.5        |
+| $\delta_1$ | Spontaneous degradation rate of mRNA                         | min$^{-1}$            | 0.2        |
+| $\delta_3$ | Spontaneous degradation rate of TP901                        | min$^{-1}$            | 0.2        |
+| $\delta_4$ | Spontaneous degradation rate of PAL                          | min$^{-1}$            | 0.2        |
+| $v_{m,1}$  | Maximum rate of T7 promoter inversion                        | min$^{-1}$            | 0.1        |
+| $v_{m,2}$  | Maximum rate of the Phe degradation                          | min$^{-1}$            | 0.1        |
+| $K_{m,1}$  | Michaelis-Menten constant for T7 promoter inversion          | mM                    | 0.5        |
+| $K_{m,2}$  | Michaelis-Menten constant for Phe degradation                | mM                    | 0.5        |
+| $\gamma_1$ | Transmembrane diffusion rates of Phe                         | min$^{-1}$            | 1          |
+| $\gamma_2$ | Transmembrane diffusion rates of TCA                         | min$^{-1}$            | 0.5        |
+| $\lambda$  | Ratio of volume of bacteria and which of solution            | None                  | 10$^{-10}$ |
+| $r$        | Unrestricted growth rate                                     | min$^{-1}$            | 0.5        |
+| $N_m$      | Enviromental capacity                                        | None                  | 10$^9$     |
+
+![](result.jpg)
+
+As shown in the figure above, when the initial TCA concentration is 0mM, the process of complete inversion of the T7 promoter is about 20 minutes slower than when the initial TCA concentration is 1mM, and it will delay the start time of TCA degradation. Under both initial TCA concentrations, all T7 promoters can be completely inverted within 40 minutes. This indicates that the presence of TCA in the environment can promote the efficiency of TP901 inversion reaction.
+
+As shown in the figure below, using the strategy of TP901 inversion promoter, although there will be a problem of slower degradation rate at the initial moment, it can ensure that under lower initial TCA concentration, the degradation of Phe is basically not affected too much. For the scheme of using TCA promoter to produce PAL, when the initial TCA concentration is 0mM, its degradation rate is relatively slow. When the TCA concentration is 1mM, the degradation rate is significantly increased. For the scheme of using T7 promoter to produce PAL, in the same TCA concentration, the initial degradation rate is lower in T7 promoter system, but the overall rate in T7 system is higher than in TCA system, regareless oof TCA concentration.
+
+Therefore, based on the above data, we choose to couple T7 promoter downstream of TP901 signal amplification system and activate TP901 with TCA promoter to better utilize TP901 integrase to improve Phe metabolism efficiency.
\ No newline at end of file

wiki/menu.html

@@ -110,7 +110,7 @@
             Dry Lab
           </a>
           <ul class="dropdown-menu" aria-labelledby="navbarDropdown">
-            <li><a class="dropdown-item" href="{{ url_for('pages', page='hardware') }}">Hardware</a></li>
+            
             <li><a class="dropdown-item" href="{{ url_for('pages', page='model') }}">Model</a></li>
 
             
@@ -124,6 +124,7 @@
           <ul class="dropdown-menu" aria-labelledby="navbarDropdown">
             <li><a class="dropdown-item" href="{{ url_for('pages', page='human-practices') }}">Human Pratices</a></li>
             <li><a class="dropdown-item" href="{{ url_for('pages', page='entrepreneurship') }}">Entrepreneurship</a></li>
+            <li><a class="dropdown-item" href="{{ url_for('pages', page='inclusivity') }}">Inclusivity</a></li>
 
             
           </ul>

wiki/pages/entrepreneurship.html

@@ -3,39 +3,150 @@
 {% block title %}Entrepreneurship{% endblock %}
 {% block cover_img %}https://static.igem.wiki/teams/5013/wiki/cover/entrepreneurship.jpg{% endblock %}
 
+{% block detail_content1 %}{% endblock %}
+{% block detail_title_a1 %}Introduction{% endblock %}
+{% block detail_content2 %}In the context of the current era of rapid development of medical technology, our team is committed to improving the quality of human life through innovative products, especially for individuals suffering from certain genetic diseases. Our main product is an E. coli-based drug. Through advanced DNA synthesis technology, we change the function of E. coli so that it can alleviate the symptoms of patients with phenylketonuria to a certain extent while limiting phenylalanine. intake. After many attempts and optimizations, we decided to provide this drug to customers in the form of milk powder for easier use and acceptance. Our vision is to promote this innovative product globally and help as many children with phenylketonuria as possible relieve their pain so that they can grow up healthily like other normal children. To achieve this goal, we closely integrate entrepreneurship with our product development, aiming to promote the dissemination and application of products through commercialization, thereby contributing to society.
+Below is our business plan
+{% endblock %}
+{% block detail_pdf1 %}https://static.igem.wiki/teams/5013/wiki/entre/pdf1.pdf{% endblock %}
+{% block detail_content3 %}{% endblock %}
+{% block detail_title_a2 %}Seminar{% endblock %}
+{% block detail_content4 %}Our team conducted in-depth discussions and research before embarking on the business plan. We discussed how to carry out commercial activities comprehensively to ensure that our innovative products can be effectively brought to market and meet the needs of target customers. We developed two business plans and identified the market research plans that needed to be conducted.
+This ensures that our products can effectively meet market demand, achieve our commercial goals, and provide effective help for children with phenylketonuria.
+{% endblock %}
+{% block detail_img1 %}https://static.igem.wiki/teams/5013/wiki/entre/img1.png{% endblock %}
+{% block detail_content5 %}Here is our workshop transcript
+{% endblock %}
+{% block detail_pdf2 %}https://static.igem.wiki/teams/5013/wiki/entre/pdf2.pdf{% endblock %}
+{% block detail_content6 %}Here is the first version of our plan
+{% endblock %}
+{% block detail_pdf3 %}https://static.igem.wiki/teams/5013/wiki/entre/pdf3.pdf{% endblock %}
+{% block detail_content7 %}Here is our second version of the plan
+{% endblock %}
+{% block detail_pdf4 %}https://static.igem.wiki/teams/5013/wiki/entre/pdf4.pdf{% endblock %}
+{% block detail_content8 %}Here is our market research content and division of labor
+{% endblock %}
+{% block detail_pdf5 %}https://static.igem.wiki/teams/5013/wiki/entre/pdf5.pdf{% endblock %}
+{% block detail_content9 %}{% endblock %}
+{% block detail_title_a3 %}PowerPoint presentation{% endblock %}
+{% block detail_content10 %}Our team also developed a PowerPoint presentation designed to detail our project, products, and business plan in order to attract the attention and support of potential investors during subsequent pitches. This presentation not only showcases the science, production processes and market potential of our products, it also highlights the strength of our team, core competencies and long-term business vision.
+We produced this PPT in the middle of our project, and we will continue to modify it later.
+Here is our PPT
+{% endblock %}
+{% block detail_pdf6 %}https://static.igem.wiki/teams/5013/wiki/entre/pdf6.pdf{% endblock %}
+{% block detail_content11 %}{% endblock %}
+{% block detail_title_a4 %}Interview with patient’s family{% endblock %}
+{% block detail_content12 %}We actively conducted in-depth communication and exchanges with the families of children with phenylketonuria, aiming to obtain valuable feedback from their actual needs and experiences. By hearing their comments and suggestions about available treatments, we gained a more comprehensive and practical understanding of treatments for phenylketonuria. This not only deepens our insight into the real needs of patients, but also allows us to optimize our product design and functionality in a targeted manner.
+{% endblock %}
+{% block detail_img2 %}https://static.igem.wiki/teams/5013/wiki/entre/img2.jpg{% endblock %}
+{% block detail_content13 %}{% endblock %}
+{% block detail_title_a5 %}Charitable foundation{% endblock %}
+{% block detail_content14 %}We hope that the profits we make will build a charitable foundation strong enough to attract like-minded people to come together and work toward a common goal. We do our best not only to help PKU patients, but also hope to treat more patients with genetic diseases in the future. So we developed a charitable foundation plan. Please see the Charitable Foundation section of our business plan for details.
+{% endblock %}
+{% block detail_img3 %}https://static.igem.wiki/teams/5013/wiki/entre/img3.png{% endblock %}
+{% block detail_content15 %}
+
+
+
+{% endblock %}
+
 {% block page_content %}
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+  
+  <!-- 侧边栏 -->
+  <div class="sidebar flex-column">
+      
+      <!-- todo -->
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+            </div>
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-<div class="row mt-4">
-  <div class="col">
-    <div class="bd-callout bd-callout-info">
-      <h4>Best Supporting Entrepreneurship</h4>
-      <p>The Best Supporting Entrepreneurship award recognizes exceptional effort to build a business case and commercialize an iGEM project. This award is open to all teams to show that entrepreneurship is something all teams can aspire to do with their project. This award can go to an new project, or to a previous project that a team aimed to commercialize. Have you filed a provisional patent on your project/device/process? Have you raised money to build and ship products? Have you pitched your idea to investors and received money? As always in iGEM, the aim is to impress the judges!</p>
-      <p>To compete for the Best Supporting Entrepreneurship prize, please describe your work on this page and also fill out the description on the <a href="https://competition.igem.org/deliverables/judging-form">judging form</a>.</p>
-      <hr>
-      <p>Please see the <a href="https://competition.igem.org/judging/awards">2023 Awards Page</a> for more information.</p>
-    </div>
   </div>
-</div>
 
-<div class="row mt-4">
-  <div class="col-lg-8">
-    <h2>Patents and intellectual property</h2>
-    <hr>
-    <p>If your team is seriously considering commercializing and looking into building a company after the competition, you may want to look at how you are going to protect your work and secure investment. Investors will usually require some form of intellectual protection, so you may want to investigate how to apply for a patent or provisional patent in your country and region before disclosing your project at iGEM. Remember that you can only be evaluated in iGEM based on what you share on your wiki and at the Jamboree, so any work you don't present can't count towards your project.</p>
-    <p>This is an area where we are different as we care about sharing, openness and contributing to the community and investors don't always agree with these values. It is up to you and your team to decide what to do. Remember that most universities have a commercialization department and that you can talk to them before coming to a decision.</p>
-  </div>
-  <div class="col-lg-4">
-    <h2>Inspirations</h2>
-    <hr>
-    <ul>
-      <li><a href="https://2019.igem.org/Team:UCopenhagen/Entrepreneurship">2019 UCopenhagen</a></li>
-      <li><a href="https://2019.igem.org/Team:Thessaly/Entrepreneurship">2019 Thessaly</a></li>
-      <li><a href="https://2019.igem.org/Team:NCKU_Tainan/Entrepreneurship">2019 NCKU Tainan</a></li>
-      <li><a href="https://2020.igem.org/Team:TAS_Taipei/Entrepreneurship">2020 TAS Taipei</a></li>
-      <li><a href="https://2020.igem.org/Team:KCL_UK/Entrepreneurship">2020 KCL UK</a></li>
-      <li><a href="https://2020.igem.org/Team:Calgary/Entrepreneurship">2020 Calgary</a></li>
-    </ul>
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+
 {% endblock %}