Difference between revisions of "Team:NAU-CHINA/Application prospects"

 
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从Mosfet到Biomosfet:
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将机器生物化,将生物工程化
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我们的系统可以将外界波动的信号转换成简单的0和1两种信号,实现模数转换器的功能。同时作为由于引入了重组酶,我们的系统作为一个生物开关理论上会更加精确,渗漏更低,信号表达量受外界诱导物浓度信号影响低,并且可以通过调节调节下游启动子和重组酶的种类,调节系统阈值。综合以上三点特性,我们的系统十分适合信息处理,如果未来能将表达信号通过光感元件转换成电信号,就可以实现我们logo上展示的图像——将生物信息转换成电子信息,将机器生物化,将生物工程化。(I think it can be deleted)
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将上游胞外域换成EGFR的抗体,我们的设计可以识别细胞膜表面上不同密度的EGFR,根据EGFR的密度判断细胞是否改变,从而实现对癌细胞的识别和攻击。
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在工业生产中,通过改造上游通路,使细胞能识别自身的产物、代谢废物或者杂菌等,根据外界条件实现生产的自动调节或提醒工作人员进行相应情况进行处理。(I think it can be deleted)
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通过替换上游通路的识别对象,可以实现对某种物质浓度的测定。而通过调节下游启动子和重组酶的种类,可以调节系统阈值,在检测物质的有和无的同时,还能实现对检测物浓度的动态检测。
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如果我们将两种细胞都装上我们的系统,使之能彼此识别并能互相抑制,那么我们就实现了群体感应功能,可以使两种细胞的数目维持在一定范围内波动,对于工业生产、物质检测有一定作用。如果使细胞发出荧光,通过细胞数目的周期性波动,可以看到荧光的周期性亮度变化,实现基因振荡器的功能。
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From Mosfet to Biomosfet:
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to make the machine biological and biology engineering
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Our system can convert the external fluctuation signals into simple 0 and 1 signals to realize the function of analog-to-digital converter. At the same time, as a result of the introduction of recombinases, our system will theoretically be more accurate as a biological switch, with lower leakage, less signal expression affected by the concentration signal of external inducers, and the system threshold can be adjusted by adjusting the types of downstream promoters and recombinases. Combined with the above three characteristics, our system is very suitable for information processing. If we can convert the expression signals into electrical signals through light sensing elements in the future, we can realize the image displayed on our LOGO ——converting biological information into electronic information, make the machine biological and make biology engineering.
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By replacing the upstream extracellular domain with EGFR antibody, our system can recognize EGFR with different density on the surface of cell membrane and judge whether the cell is cancerous or not according to the density of EGFR, thus realizing accurate recognition and attack of cancer cells.(this part need write more! This is our mainly background)
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In the process of industrial production, by modifying the upstream channel, cells can identify their own products, metabolic wastes or miscellaneous bacteria, etc., and realize automatic adjustment of production according to external conditions or remind workers to deal with corresponding situations.
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By replacing the identification object of the upstream system, the measurement of a certain substance can be realized. By adjusting the types of downstream promoters and recombinases, the system threshold can be adjusted.Then the system can not only detect the presence or absence of substances but also dynamically detect the concentration of the detected substances .
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If we install our system in two kinds of cells so that they can recognize each other and inhibit each other, then we can realize the function of group sensing, which can keep the number of two kinds of cells fluctuating within a certain range. And this will play a important role in industrial production, material detection and other fields. If the cells are made to emit fluorescence, the periodic brightness changes of fluorescence can be seen through periodic fluctuations in the number of cells, thus realizing the function of repressilator.
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        <p class="top-title">PROJECT</p>
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        <p class="sec-title">Application prospects</p>
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    <a href="https://2018.igem.org/Team:NAU-CHINA/Overview">
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    <a href="https://2018.igem.org/Team:NAU-CHINA/Design">
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            <h1>From Mosfet to MOSFET</h1>           
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            <p>Our system can convert externally-fluctuating signals into simple 0 and 1 signals to realize the function of an analog-to-digital converter. At the same time, because of the introduction of recombinases, our system will theoretically be more accurate as a biological switch, with lower leakage and less signal expression affected by the concentration of external inducers.  </p>
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            <p>Due to the characteristics of the recombinases we used, the engineered cells of our subject can change different concentrations of signals from the outside into two kinds of simple outputs, and the threshold can be changed by changing the types of the promoter and the recombinase.</p>
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            <p>Based on these considerations above, our engineered cells can be used in the following situations:</p>
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            <h1>Precision-targeted therapy for solid tumors</h1>           
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            <p>EGFR (epidermal growth factor receptor) is a very important protein for cell growth and differentiation that exists on the surface of both normal cells and cancer cells.  When a  ligand binds to EGFR, EGFR will be activated and send a signal to the inside of the cell to control cell growth through the cell pathway.</p>
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            <p> However, compared with normal cells, many cancer cells have mutations resulting in overexpression of EGFR. When the ligand is attached to the mutated EGFR, this signal will remain in "sent" mode all the time, resulting in uncontrolled cell response and growth and.  Different EGFR mutations lead to different kinds of cancers<sup>[1]</sup>, such as non-small cell lung cancer, pancreatic cancer, breast cancer, medullary thyroid cancer, head and neck squamous cell cancer, colorectal cancer, chordoma, and malignant glioma.</p>
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            <p> Since the traditional cancer treatment methods, such as radiotherapy and chemotherapy, can kill all rapidly growing cells in addition to the actual cancer cells, there will be many side effects.  Even targeted therapy may also have certain side effects because the target also exists in normal cells<sup>[2]</sup>. Immunotherapy may also damage normal cells due to the strong immune response of the modified T cells<sup>[3]</sup>, so it is necessary to use an immune checkpoint inhibitor to adjust the intensity of the immune response.  However, the use of immunosuppressive agents can also do some harm to the human body.</p>
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            <p> If we replace the upstream extracellular domain of our subject with EGFR antibodies, our design can accurately identify EGFR with different densities on the cell membrane surface, and judge whether the cells change according to the density of EGFR, thus enabling recognition of cancer cells. Moreover, we can adjust the immune strength of the engineered immune cells and the threshold value of EGFR recognition by adjusting the promoter strength and the type of recombinase, to accurately distinguish normal cells with low density EGFR from cancerous cells with high density EGFR, protecting normal cells to the maximum extent, while recognizing and killing cancerous cells. We have devised two strategies to achieve this.</p>
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            <p>1. Make the final secretion for the whole set of switches PD-1 and PD-L1 antibodies such as MPDL3280A, MEDI4736 BMS-936559, Nivolumab and Pembrolizumab<sup>[4]</sup>,  to make the T cells identify and kill cancer cells through other surface molecules.  Compared with the direct use of antibodies by injection therapy, our method of modifying T cells makes the antibody therapy more targeted and minimizes the damage to other immune cells in the body.</p>
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            <p>2. Make the whole set of switches finally secrete some molecules such as IL-12, CCL21 and so on<sup>[5]</sup>. These molecules have the function of stimulating the growth and function of T cells, thus strengthening their ability to kill cancer cells.</p>
  
关于这部分,我觉得我们要以一个主要的application background,目前就是EGFR,之前HP部分有查过关于EGFR的内容,在写网页的时候可以参考,而其他application background我觉得可以少些一些。EGFR的思路大致如此:首先要将一下他的背景,然后就是我们的工程T cell,我们的工程T cell的设计能够实现绝对的01化,这样的好处是。。。。可以具体问LPK。比如释放毒素杀伤肿瘤细胞,或者招募其他免疫细胞来杀伤肿瘤细胞,在这个过程中,我是否给药需要一个绝对的01开关来保证安全性。
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            <h1>More future application prospects</h1>           
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            <p>In addition, by replacing the identification object of the upstream system, the measurement of a certain substance can be realized. By adjusting the types of downstream promoters and recombinases, the system threshold can be adjusted. The system may then be used not only to detect the presence or absence of substances but also to dynamically detect the concentration of the detected substances.
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            </p>
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            <p>If we install our system in two kinds of cells so that they can recognize each other and inhibit each other’s activity and growth, then we can realize the function of group sensing, which can keep the number of two kinds of cells fluctuating within a certain range. This will play an important role in industrial production, material detection and other fields. If the cells are made to emit fluorescence, periodic brightness changes of fluorescence will reflect periodic fluctuations in the number of cells, thus realizing the function of repressilator.</p>
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            <h1>Reference</h1>
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            <p>[1] Sigismund, S., Avanzato, D. & Lanzetti, L. Emerging functions of the EGFR in cancer. Mol. Oncol. 12, 3–20 (2018).</p>
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            <p>[2] Kalos, M. & June, C. H. Review Adoptive T Cell Transfer for Cancer Immunotherapy in the Era of Synthetic Biology. Immunity 39, 49–60 (2013).</p>
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            <p>[3] Rubens, J. R., Selvaggio, G. & Lu, T. K. Synthetic mixed-signal computation in living cells. Nat. Commun. 7, 1–10 (2016).</p>
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            <p>[4] Lote, H., Cafferkey, C. & Chau, I. PD-1 and PD-L1 blockade in gastrointestinal malignancies. Cancer Treat. Rev. 41, 893–903 (2015).</p>
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            <p>[5] Nissim, L. et al. Synthetic RNA-Based Immunomodulatory Gene Circuits for Cancer Immunotherapy. Cell 171, 1138–1150.e15 (2017).</p>
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Latest revision as of 03:03, 18 October 2018

Template:2018_NAU-CHINA

header
InterLab

PROJECT

Application prospects

From Mosfet to MOSFET

Our system can convert externally-fluctuating signals into simple 0 and 1 signals to realize the function of an analog-to-digital converter. At the same time, because of the introduction of recombinases, our system will theoretically be more accurate as a biological switch, with lower leakage and less signal expression affected by the concentration of external inducers.

Due to the characteristics of the recombinases we used, the engineered cells of our subject can change different concentrations of signals from the outside into two kinds of simple outputs, and the threshold can be changed by changing the types of the promoter and the recombinase.

Based on these considerations above, our engineered cells can be used in the following situations:

Precision-targeted therapy for solid tumors

EGFR (epidermal growth factor receptor) is a very important protein for cell growth and differentiation that exists on the surface of both normal cells and cancer cells. When a ligand binds to EGFR, EGFR will be activated and send a signal to the inside of the cell to control cell growth through the cell pathway.

However, compared with normal cells, many cancer cells have mutations resulting in overexpression of EGFR. When the ligand is attached to the mutated EGFR, this signal will remain in "sent" mode all the time, resulting in uncontrolled cell response and growth and. Different EGFR mutations lead to different kinds of cancers[1], such as non-small cell lung cancer, pancreatic cancer, breast cancer, medullary thyroid cancer, head and neck squamous cell cancer, colorectal cancer, chordoma, and malignant glioma.

Since the traditional cancer treatment methods, such as radiotherapy and chemotherapy, can kill all rapidly growing cells in addition to the actual cancer cells, there will be many side effects. Even targeted therapy may also have certain side effects because the target also exists in normal cells[2]. Immunotherapy may also damage normal cells due to the strong immune response of the modified T cells[3], so it is necessary to use an immune checkpoint inhibitor to adjust the intensity of the immune response. However, the use of immunosuppressive agents can also do some harm to the human body.

If we replace the upstream extracellular domain of our subject with EGFR antibodies, our design can accurately identify EGFR with different densities on the cell membrane surface, and judge whether the cells change according to the density of EGFR, thus enabling recognition of cancer cells. Moreover, we can adjust the immune strength of the engineered immune cells and the threshold value of EGFR recognition by adjusting the promoter strength and the type of recombinase, to accurately distinguish normal cells with low density EGFR from cancerous cells with high density EGFR, protecting normal cells to the maximum extent, while recognizing and killing cancerous cells. We have devised two strategies to achieve this.

1. Make the final secretion for the whole set of switches PD-1 and PD-L1 antibodies such as MPDL3280A, MEDI4736 BMS-936559, Nivolumab and Pembrolizumab[4], to make the T cells identify and kill cancer cells through other surface molecules. Compared with the direct use of antibodies by injection therapy, our method of modifying T cells makes the antibody therapy more targeted and minimizes the damage to other immune cells in the body.

2. Make the whole set of switches finally secrete some molecules such as IL-12, CCL21 and so on[5]. These molecules have the function of stimulating the growth and function of T cells, thus strengthening their ability to kill cancer cells.

More future application prospects

In addition, by replacing the identification object of the upstream system, the measurement of a certain substance can be realized. By adjusting the types of downstream promoters and recombinases, the system threshold can be adjusted. The system may then be used not only to detect the presence or absence of substances but also to dynamically detect the concentration of the detected substances.

If we install our system in two kinds of cells so that they can recognize each other and inhibit each other’s activity and growth, then we can realize the function of group sensing, which can keep the number of two kinds of cells fluctuating within a certain range. This will play an important role in industrial production, material detection and other fields. If the cells are made to emit fluorescence, periodic brightness changes of fluorescence will reflect periodic fluctuations in the number of cells, thus realizing the function of repressilator.

Reference

[1] Sigismund, S., Avanzato, D. & Lanzetti, L. Emerging functions of the EGFR in cancer. Mol. Oncol. 12, 3–20 (2018).

[2] Kalos, M. & June, C. H. Review Adoptive T Cell Transfer for Cancer Immunotherapy in the Era of Synthetic Biology. Immunity 39, 49–60 (2013).

[3] Rubens, J. R., Selvaggio, G. & Lu, T. K. Synthetic mixed-signal computation in living cells. Nat. Commun. 7, 1–10 (2016).

[4] Lote, H., Cafferkey, C. & Chau, I. PD-1 and PD-L1 blockade in gastrointestinal malignancies. Cancer Treat. Rev. 41, 893–903 (2015).

[5] Nissim, L. et al. Synthetic RNA-Based Immunomodulatory Gene Circuits for Cancer Immunotherapy. Cell 171, 1138–1150.e15 (2017).

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