Difference between revisions of "Team:Stockholm"

 
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<h2>ABBBA: Affibody-Based Bacterial Biomarker Assay </h2>
  
<h1> With “ABBBA” against Cancer </h1>
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<p>Early diagnosis is important for patient prognosis. As a rule of thumb, the earlier a disease is diagnosed, the better the odds for recovery. Studies show that treatment for many different diseases (e.g. cancer) is more efficient when therapy is started at an early stage.  Yet, reliable, sensitive and easily applicable diagnostic tools are still lacking.</p>
  
<p>Although many effective treatments for cancer are already available, it still represents the leading cause of death worldwide Why is this so? Many cancer types are very difficult to detect with nowadays techniques. This makes it for physicians and lab technicians difficult to catch the disease when it is the most vulnerable - right at its beginning. Studies showed that treatment for many different diseases, far beyond the cancer field, are more efficiency when the therapy is started in an early diseases state.Unfortunately, modern medicine has not yet found an appropriate diagnostic tool to overcome detection of small quantities of biomarkers.
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<p>iGEM Stockholm 2015, consisting of students from Karolinska Institutet and the Royal Institute of Technology, KTH, is developing a novel technique to measure even small amounts of disease biomarker in body fluids. It's an "Affibody-Based Bacterial Biomarker Assay", and we call it ABBBA.</p>
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<p>The iGEM Team Stockholm, consisting of students from Karolinska Institutet and the Royal Institute of Technology KTH, has made it their task to develop a novel technique to measure even small amounts of disease biomarker in body fluids, the “Affibody-Based Bacterial Biomarker Assay” (ABBBA). This method will be a biological measure to overcome thresholds of most chemically based diagnostic methods which are the canonical tool in clinics. In our new assay, we will sensitize bacteria specifically towards a certain disease antigen (e.g. HER-2, a marker for breast cancer cells) by creating a new fusion receptor consisting of a strong antigen binder, called Affibody molecule, and a membrane-standing signal transduction domain. As soon as the antigen binds to the Affibody molecule it will trigger a signaling cascade within the cell leading to an increased production of fluorescent molecules which can be read-out.
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<img src="https://static.igem.org/mediawiki/2015/9/97/Affibody_infographic_panel.png" alt="ABBBA Affibody panel" class="img-responsive padded-image"/>
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<p>  With this assay, small concentrations of biomarker in body fluid samples, which are currently not measurable, will no longer be overlooked. This will hopefully lead to an earlier disease diagnosis and increased survival chances for the patients.
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<p>As proof-of-principle, we wanted to sensitize <i>E. coli</i> against the cancer biomarker human epidermal growth factor receptor-2 (HER-2) by creating a chimeric receptor. We used the Affibody molecule – a strong molecular binder and the osmoregulator EnvZ originating from <i>E. coli</i>. Exploiting the EnvZ-OmpR signaling cascade, we wanted to transduce a signal from binding into the cell. In our circuit, this event regulates a differential expression of two quorum sensing molecules depending on the presence of the biomarker. A co-cultured strain will then detect these quorum sensing molecules and express fluorescence.</p>
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<p>Our project integrates the power of different fields of modern biology such as biomedicine, structural biology, biotechnology, molecular biology and bioinformatics. With the support of our universities and different external partner such as Atlas Antibodies, HealthCap, Sigma-Aldrich, Qiagen, GATC Biotech, BioBasic Ink., Eppendorf and Snapgene, we want to show a new way in early disease diagnosis.
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<img src="https://static.igem.org/mediawiki/2015/5/5c/Receptor_and_signaling_wiki_panel.png" alt="ABBBA Affibody panel" class="img-responsive"/>
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<h2>Do you want to help?
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<p>In the time frame of the project, we synthesized three biobricks of a chimeric bacterial antigen receptor. We have shown the expression of all the receptors in <i>E. coli</i>. The biomarker HER-2 interacts with at least one of these receptors. We also characterized an OmpR dependent biobrick expressing RFP, which we later exchanged with a quorum synthase. Furthermore, we partially characterized a read-out strain which expresses RFP in response to quorum sensing.</p>
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<p>Any and all sponsorship is welcome and appreciated! We have created a crowd funding site to help our friends, family, and fans support the project! Click <a href="https://www.rockethub.com/projects/58524-bacteria-that-detect-disease-an-affibody-based-bacterial-biomarker-assay#description-tab">here</a>to make a donation of any amount and be rewarded with cool Stockholm iGem swag!
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<p>We have also cooperated on science and social issues with teams from Sweden, Switzerland, Israel, Germany, France, Finland and Taiwan.</p>
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Latest revision as of 23:14, 18 September 2015

ABBBA: Affibody-Based Bacterial Biomarker Assay

Early diagnosis is important for patient prognosis. As a rule of thumb, the earlier a disease is diagnosed, the better the odds for recovery. Studies show that treatment for many different diseases (e.g. cancer) is more efficient when therapy is started at an early stage. Yet, reliable, sensitive and easily applicable diagnostic tools are still lacking.

iGEM Stockholm 2015, consisting of students from Karolinska Institutet and the Royal Institute of Technology, KTH, is developing a novel technique to measure even small amounts of disease biomarker in body fluids. It's an "Affibody-Based Bacterial Biomarker Assay", and we call it ABBBA.

ABBBA Affibody panel

As proof-of-principle, we wanted to sensitize E. coli against the cancer biomarker human epidermal growth factor receptor-2 (HER-2) by creating a chimeric receptor. We used the Affibody molecule – a strong molecular binder – and the osmoregulator EnvZ originating from E. coli. Exploiting the EnvZ-OmpR signaling cascade, we wanted to transduce a signal from binding into the cell. In our circuit, this event regulates a differential expression of two quorum sensing molecules depending on the presence of the biomarker. A co-cultured strain will then detect these quorum sensing molecules and express fluorescence.

ABBBA Affibody panel

In the time frame of the project, we synthesized three biobricks of a chimeric bacterial antigen receptor. We have shown the expression of all the receptors in E. coli. The biomarker HER-2 interacts with at least one of these receptors. We also characterized an OmpR dependent biobrick expressing RFP, which we later exchanged with a quorum synthase. Furthermore, we partially characterized a read-out strain which expresses RFP in response to quorum sensing.

We have also cooperated on science and social issues with teams from Sweden, Switzerland, Israel, Germany, France, Finland and Taiwan.