Difference between revisions of "Team:UPF CRG Barcelona/Description"

 
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         <h1>Project Description</h1>
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          <a class="navbar-logo" href="https://2018.igem.org/Team:UPF_CRG_Barcelona">
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            <img src="https://static.igem.org/mediawiki/2018/3/37/T--UPF_CRG_Barcelona--logosensebarcelona.svg" alt="iGEM Barcelona team 2018">
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        <h2>Abstract</h2>
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             Metastasis causes up to 90% of deaths related to the presence of tumors. Recent studies have shown that metastasis can be
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             initiated by over-expression of a fatty acid receptor (CD36). Also, it has been shown that metastasis development
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             depends directly on long chain fatty acid (LCFA) dietary uptake, particularly palmitic acid (PA). Since most
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             foods contain LCFA, it would be unfeasible its avoidance by dietary restriction, therefore developing a system
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             capable of reducing its intestinal absorption could be a new approach to tackle metastasis. We plan to use synthetic
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             <a class="navbar-item is-active" href="https://2018.igem.org/Team:UPF_CRG_Barcelona/Description">Project</a>
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             biology to design a probiotic with increased fatty acid uptake and with PA specificity. By decreasing PA concentration
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            <a style="color: rgb(242, 242, 242)" class="navbar-item" href="https://2018.igem.org/Team:UPF_CRG_Barcelona/DryLab">DryLab</a>
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             in the intestinal lumen and consequently its absorption and blood levels, we expect preventing it from being
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            used as an energy source for metastatic cells.
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             <a style="color: rgb(242, 242, 242)" class="navbar-item" href="https://2018.igem.org/Team:UPF_CRG_Barcelona/Deliverables">Deliverables</a>
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             <a style="color: rgb(242, 242, 242)" class="navbar-item" href="https://2018.igem.org/Team:UPF_CRG_Barcelona/WetLab">WetLab</a>
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             <a style="color: rgb(242, 242, 242)" class="navbar-item" href="https://2018.igem.org/Team:UPF_CRG_Barcelona/intro_HP">Human Practices</a>
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             <a style="color: rgb(242, 242, 242)" class="navbar-item" href="https://2018.igem.org/Team:UPF_CRG_Barcelona/Aboutteam">Team</a>
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        <h2>Introduction</h2>
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            Metastasis occurs when a cancer spreads from the original tumor to other parts of the body. Currently, controlling metastasis
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            is still a challenge and causes up to 90% of deaths related to the presence of tumors (Mehlen & Puisieux, 2006).
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            It has recently been shown that a fat component, called palmitic acid, can cause metastasis in tumor cells (Pascual
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          <a class="swiper-slide swiper-slide-menu" href="https://2018.igem.org/Team:UPF_CRG_Barcelona/Background">
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            et al., 2017). A main problem here is that palmitic acid is found in many foods so dietary restriction is not
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            possible.
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             <p>Background<br>and design</p>
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            On the other hand, in our gut we find millions of bacteria, which are known as the intestinal microbiota (Gerritsen, Smidt,
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             <p>Overexpression</p>
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            Rijkers, & de Vos, 2011). These bacteria perform many beneficial functions. We had the following idea: What if
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            we could develop a gut microorganism, capable of up taking palmitic acid and acting as a fatty acid sponge? Achieving
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            so would provide us with a potential mechanism for combating metastasis, and it could also be applied to treat
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            other metabolic diseases.
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            <p>Biosensor</p>
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            The study, which is the central idea of our project, has described that cancer cells expressing high levels CD36 receptor,
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             <p>Integration</p>
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            a long chain fatty acid scavenger receptor, are more likely to initiate metastasis in the presence of an excess
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            of dietary fat. Hence, overexpression of CD36 in cell lines increased their potential to metastasize. Besides,
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            this study also showed that the presence of CD36+ metastasis-initiating cells correlates clinically with a poor
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            prognosis.
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            <p>Simulation</p>
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            With these recent findings, a CD36-based anti-metastatic therapy has been proposed, in which the use of anti-CD36 neutralizing
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            <p>Results</p>
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            antibodies would block fatty acid intake in cancer cells and thus its ability to develop metastasis.
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            In an attempt to propose an alternative approach to the already existing antibody, our project intents to benefit from the
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            presence of bacteria in our intestines. Thus, we aim to design a probiotic with an enhanced metabolism able to
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            increase fatty acid absorption. Our goal is to reduce palmitic acid intestinal absorption, since its presence
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            in most foods makes unfeasible its avoidance by dietary restriction. By doing so we could halt tumor cells from
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             becoming metastatic.
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            We believe that our probiotic would serve as a complementary approach, with low cost and accessible in places where an infrastructure
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            for administration of antibodies is not yet available. Once we develop our system, we plant to further optimize
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            it for the use in the treatment of other metabolic diseases.
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            <ul>
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                <li>Aim 1: Design a proof of concept of a probiotic with enhanced FA uptake using the following strategies:</li>
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                    <li>Overexpression of bacterial endogenous proteins related with FA absorption.</li>
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                        Directed evolution for increasing the efficiency of the system (multiplex automated genome engineering and other strategies).
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                    </li>
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                        Nature inspired design: explore and reproduce mechanisms that are used in bacteria that live in a high FA environment.
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                    <li>Engineer bacterial response mechanisms to environmental fatty acid energy sources.</li>
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                    Aim 2: Demonstrate that our system efficiently prevents metastasis in-vitro by removing palmitic acid from growth media.
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                    Our strategy is to co-culture them with tumor cells.
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                </li>
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                <li>Aim 3: Plan a study based on the administration of our probiotic in rodent models.</li>
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                    Aim 4: Develop a strategy to explore how we can expand the use of our fatty acid sponge to treat other metabolic diseases
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                    and broader applications of our probiotic.
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                </li>
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        <h2>References</h2>
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            Gerritsen, J., Smidt, H., Rijkers, G. T., & de Vos, W. M. (2011). Intestinal microbiota in human health and disease: the
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            impact of probiotics. Genes & nutrition.
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        <p>Mehlen, P., & Puisieux, A. (2006). Metastasis: A question of life or death. Nature Reviews Cancer.</p>
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            Pascual, G., Avgustinova, A., Mejetta, S., Martín, M., Castellanos, A., Attolini, C. S. O., Berenguer, A., et al. (2017).
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            Targeting metastasis-initiating cells through the fatty acid receptor CD36. Nature.
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        <p>Tell us about your project, describe what moves you and why this is something important for your team.</p>
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        <h3>What should this page contain?</h3>
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            <li> A clear and concise description of your project.</li>
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            <li>A detailed explanation of why your team chose to work on this particular project.</li>
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             <li>References and sources to document your research.</li>
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            <li>Use illustrations and other visual resources to explain your project.</li>
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            <h3>Inspiration</h3>
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             <p>See how other teams have described and presented their projects: </p>
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                    <a href="https://2016.igem.org/Team:Imperial_College/Description">2016 Imperial College</a>
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                </li>
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                <li>
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                    <a href="https://2016.igem.org/Team:Wageningen_UR/Description">2016 Wageningen UR</a>
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                </li>
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                    <a href="https://2014.igem.org/Team:UC_Davis/Project_Overview"> 2014 UC Davis</a>
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                </li>
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                <li>
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                    <a href="https://2014.igem.org/Team:SYSU-Software/Overview">2014 SYSU Software</a>
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                </li>
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            </ul>
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        <h3>Advice on writing your Project Description</h3>
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            We encourage you to put up a lot of information and content on your wiki, but we also encourage you to include summaries
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            as much as possible. If you think of the sections in your project description as the sections in a publication,
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            you should try to be concise, accurate, and unambiguous in your achievements.
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        </p>
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        <p class="page-title">PROJECT DESCRIPTION</p>
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        <embed style="max-width: 1000px" src="https://static.igem.org/mediawiki/2018/6/6c/T--UPF_CRG_Barcelona--page_description.svg" alt="Description">
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        <h3>References</h3>
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        <p>iGEM teams are encouraged to record references you use during the course of your research. They should be posted
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            somewhere on your wiki so that judges and other visitors can see how you thought about your project and what
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            works inspired you.</p>
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Latest revision as of 00:35, 18 October 2018

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PROJECT DESCRIPTION