Difference between revisions of "Team:CSU CHINA/Description"

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<h3>★  ALERT! </h3>
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<p>This page is used by the judges to evaluate your team for the <a href="https://2019.igem.org/Judging/Medals">medal criterion</a> or <a href="https://2019.igem.org/Judging/Awards"> award listed below</a>. </p>
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              Introduction
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          Triple-negative breast cancer (TNBC), is a special subtype of breast cancer with a poor overall prognosis. Among all breast cancer patients in China, TNBC accounts for about 10-20% of breast cancer. It is more likely to occur in relatively young women, our of its highly invasive and easy to prone to visceral metastasis. The poor prognosis of TNBC is the difficulty in clinical treatment. So gene targeting TNBC is one of the best treatments of choice in the future years.
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          In this way, we choose to treat TNBC with synthetic biology by the light of nature. In order to treat the TNBC, we design three modules to solve the main two difficulties: specificity and heterogeneity. Our inspiration came from that ‘Synthetic RNA-Based Immunomodulatory Gene Circuits for Cancer Immunotherapy’. They comprised de novo synthetic cancer-specific promoters and, to enhance specificity, an RNA-based AND gate that generates combinatorial immunomodulatory outputs only when both promoters are mutually active (Figure1). So we are lighted to design the control gene circuit including specific promoter, sponge structure and miR-BS, and finally to trigger the death of the TNBC cells.
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          In short, the three modules each performs their own functions and integrated tightly: Module1 is used to identify the normal cell and cancer cell;  Module2 enhance the specificity of the identical system and also capture the heterogeneous cancer cells. Module3 is a killer to trigger death of the cancer cells which we proposed to design a HIF1αODDD-yCD fusion protein to convert 5-FC to toxic 5-FU [2]. For more information, you guys can go to the following pages!
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          <img class="col-sm-6" style="width:100%;border-radius:4%;"  src="https://static.igem.org/mediawiki/2019/d/d6/T--CSU_CHINA--IS_figure1.png" />
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      <div class="largeword">Description</div>
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                  <span style="font-size: 2.2rem;color: rgb(30, 36, 39);"> Breast cancer </span> known as one of the most infamous cancer, is the leading cause of death of cancer among women worldwide.
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              <img class="n1 col-sm-6" style="width:100%"  src="https://static.igem.org/mediawiki/2019/a/a6/T--CSU_CHINA--DES_figure1.png" />
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              Breast cancer can be had by male, due to the fact that breast existing in both male and female. The breast is mainly composed of fatty tissue. More glandular tissue making up 12 to 20 mammary lobules in which milk is produced can usually be found in women’s breast than men’s.
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              Breast epithelial cells are not regulated by the body and are constantly multiplying due to variety of reasons such as genetic mutations and epigenetic changes, which will gradually compress the surrounding tissue and form a lump. This is the beginning of cancer.
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            <img class="n3 col-sm-6" style="width:100%"  src="https://static.igem.org/mediawiki/2019/f/fb/T--CSU_CHINA--DES_figure3.png" />
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          <img class="n4 col-sm-6" style="width:80%"  src="https://static.igem.org/mediawiki/2019/f/f8/T--CSU_CHINA--DES_figure4.png" />
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                Breast cancer is also a highly heterogeneous cancer. Usually it is classified into four types based on the combination of ER, PR and HER2 receptor molecules on the cell surface.
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            Clinically, several drugs such as tamoxifen and raloxifene have been developed for ER based on the fact that it is a characteristic of Luminal A and B to inhibit the uptake of estrogen by cancer cells, thereby inhibiting the proliferation of cancer cells. Similarly, monoclonal antibody Trastuzumab was used against HER2+ positive breast cancer cells by block the HER2+ receptor and inhibiting EGF absorption, thereby preventing further proliferation of cancer cells.
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          <img class="n5 col-sm-6" style="width:100%"  src="https://static.igem.org/mediawiki/2019/b/b7/T--CSU_CHINA--DES_figure5.png" />
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            Clinically, several drugs such as tamoxifen and raloxifene have been developed for ER based on the fact that it is a characteristic of Luminal A and B to inhibit the uptake of estrogen by cancer cells, thereby inhibiting the proliferation of cancer cells. Similarly, monoclonal antibody Trastuzumab was used against HER2+ positive breast cancer cells by block the HER2+ receptor and inhibiting EGF absorption, thereby preventing further proliferation of cancer cells.
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          However, marker molecules such as ER, PR and HER2 are not present in some cancer cells which is called triple-negative breast cancer (TNBC), so there is no effective targeted therapy for these kinds of cancers. This type of cancer is aggressive, fatal and difficult to treat.
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        <h3>References:</h3>
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        <p>[1] Lior Nissim, Ming-Ru Wu, Erez Pery, Adina Binder-Nissim, Hiroshi I. Suzuki, Doron Stupp, Claudia Wehrspaun, Yuval Tabach, Phillip A. Sharp, and Timothy K. Lu, Cell, (2017),Synthetic RNA-Based Immunomodulatory Gene Circuits for Cancer Immunotherapy.</p>
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        <p>[2] Tiana D. Warren,† Krishna Patel,† James R. Eshleman,‡,§ and Marc Ostermeier, ACS Synth. Biol, Protein-Programmed Accumulation of Yeast Cytosine Deaminase in Cancer Cells in Response to Mock-Hypoxia.</p>
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<h1>Project Inspiration and Description </h1>
 
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<h3>NEW: Bronze Medal Criterion #4</h3>
 
  
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<p>Document how and why you chose your iGEM project on this page. Reference work outside or inside of iGEM that inspired your project, how you selected your project goal, and why you thought this project was a useful application of synthetic biology. Finally, provide a clear and concise description of what you plan on doing for your project.</p>
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<p>See how other teams have described and presented their projects: </p>
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<li><a href="https://2016.igem.org/Team:Imperial_College/Description">2016 Imperial College</a></li>
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<li><a href="https://2014.igem.org/Team:UC_Davis/Project_Overview"> 2014 UC Davis</a></li>
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Latest revision as of 20:12, 5 December 2019

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CSU_CHINA_TEAM
Introduction
Triple-negative breast cancer (TNBC), is a special subtype of breast cancer with a poor overall prognosis. Among all breast cancer patients in China, TNBC accounts for about 10-20% of breast cancer. It is more likely to occur in relatively young women, our of its highly invasive and easy to prone to visceral metastasis. The poor prognosis of TNBC is the difficulty in clinical treatment. So gene targeting TNBC is one of the best treatments of choice in the future years.
In this way, we choose to treat TNBC with synthetic biology by the light of nature. In order to treat the TNBC, we design three modules to solve the main two difficulties: specificity and heterogeneity. Our inspiration came from that ‘Synthetic RNA-Based Immunomodulatory Gene Circuits for Cancer Immunotherapy’. They comprised de novo synthetic cancer-specific promoters and, to enhance specificity, an RNA-based AND gate that generates combinatorial immunomodulatory outputs only when both promoters are mutually active (Figure1). So we are lighted to design the control gene circuit including specific promoter, sponge structure and miR-BS, and finally to trigger the death of the TNBC cells.
In short, the three modules each performs their own functions and integrated tightly: Module1 is used to identify the normal cell and cancer cell; Module2 enhance the specificity of the identical system and also capture the heterogeneous cancer cells. Module3 is a killer to trigger death of the cancer cells which we proposed to design a HIF1αODDD-yCD fusion protein to convert 5-FC to toxic 5-FU [2]. For more information, you guys can go to the following pages!
Description
Breast cancer known as one of the most infamous cancer, is the leading cause of death of cancer among women worldwide.
Breast cancer can be had by male, due to the fact that breast existing in both male and female. The breast is mainly composed of fatty tissue. More glandular tissue making up 12 to 20 mammary lobules in which milk is produced can usually be found in women’s breast than men’s.
Breast epithelial cells are not regulated by the body and are constantly multiplying due to variety of reasons such as genetic mutations and epigenetic changes, which will gradually compress the surrounding tissue and form a lump. This is the beginning of cancer.
Breast cancer is also a highly heterogeneous cancer. Usually it is classified into four types based on the combination of ER, PR and HER2 receptor molecules on the cell surface.
Clinically, several drugs such as tamoxifen and raloxifene have been developed for ER based on the fact that it is a characteristic of Luminal A and B to inhibit the uptake of estrogen by cancer cells, thereby inhibiting the proliferation of cancer cells. Similarly, monoclonal antibody Trastuzumab was used against HER2+ positive breast cancer cells by block the HER2+ receptor and inhibiting EGF absorption, thereby preventing further proliferation of cancer cells.
Clinically, several drugs such as tamoxifen and raloxifene have been developed for ER based on the fact that it is a characteristic of Luminal A and B to inhibit the uptake of estrogen by cancer cells, thereby inhibiting the proliferation of cancer cells. Similarly, monoclonal antibody Trastuzumab was used against HER2+ positive breast cancer cells by block the HER2+ receptor and inhibiting EGF absorption, thereby preventing further proliferation of cancer cells.
However, marker molecules such as ER, PR and HER2 are not present in some cancer cells which is called triple-negative breast cancer (TNBC), so there is no effective targeted therapy for these kinds of cancers. This type of cancer is aggressive, fatal and difficult to treat.

References:

[1] Lior Nissim, Ming-Ru Wu, Erez Pery, Adina Binder-Nissim, Hiroshi I. Suzuki, Doron Stupp, Claudia Wehrspaun, Yuval Tabach, Phillip A. Sharp, and Timothy K. Lu, Cell, (2017),Synthetic RNA-Based Immunomodulatory Gene Circuits for Cancer Immunotherapy.

[2] Tiana D. Warren,† Krishna Patel,† James R. Eshleman,‡,§ and Marc Ostermeier, ACS Synth. Biol, Protein-Programmed Accumulation of Yeast Cytosine Deaminase in Cancer Cells in Response to Mock-Hypoxia.



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