Previous Evry iGEM
Cancer thrives by preventing the immune system from targeting tumor cells. While current immunotherapies use dendritic cells to activate T-cells towards specific tumor antigens, they remain expensive and of variable efficiency against tumor immunosuppressive environment. To develop personalized therapies, our team focused on engineering yeast Saccharomyces cerevisiae for targeted immunotherapy. First, we developed a software to select the best tumor antigen from patient sequencing data. Second, we created a yeast chassis to prime the immune system with the targeted antigen. This chassis was tested in vitro on mouse splenocytes and in vivo on mice presenting melanoma with significant results. Three complementary strategies were combined to induce the immune system. First, in order to modulate the tumor environment, yeast secreting the specific immune modulator IFNgamma was encapsulated into alginate beads to be injected in tumors. Secondly, to break the immune tolerance against cancer cells, T4 and T8 lymphocytes were elicited by a yeast antigen display system that can be adapted to any tumor antigen for personalized therapy. Last, to deliver cytotoxic compounds solely in the tumor environment, a yeast hypoxia bio-sensor was designed. Our standardized and customizable chassis takes advantage of these approaches to make personalized medicine a reality, with a scalable cancer therapy.
The sponge can filtrate up to 20m3 of water/day/kg making it one of the most powerful filtrating system alive. Pseudovibrio denitrificans has been shown to be part of several sponges microbiome. Our project is based on the engineering of this bacterium in order to develop a filtrating system allowing to sense and even degrade pollutants in water when cooperating with sponges.
Our project focuses on developing a novel treatment for hematological disorders caused by an iron overload, such as hemochromatosis and thalassemia. These autosomal recessive disorders have symptoms including cirrhosis, arthritis, and heart failure, which result from overabsorption of iron from the duodenum. Although these are among the most common heritable diseases, treatment options are limited. Even today patients are mostly treated by frequent bloodletting, which many people cannot support. The aim of our project is to combat these diseases at the source by developing a therapy that prevents the intestinal absorption of iron. We engineer the Escherichia coli Ferric Uptake Regulation (FUR) system using a genetic inverter so that they produce siderophores (iron chelators) in response of high concentrations of iron. These engineered bacteria are delivered to the patient's intestine by encapsulating them in an ingestible polymer (capsule) that specifically degrades in the duodenum. Once released into the intestine, the bacteria respond to ambient iron by secreting elevated levels of siderophores, thereby chelating the iron to prevent its absorption by the patient.
For our first participation in iGEM, we have decided to introduce a new organism to the competition: Xenopus tropicalis. Its common name is the Western clawed frog, a diploid cousin of the model organism Xenopus laevis. Aside for the soft spot French have for frogs, we also believe Xenopus could be a great multicellular chassis for synthetic biology. We are therefore bringing this organism to iGEM for the first time, along with the tools we need to bring Synthetic biology to the multicellular era. The laboratory part of our work can be divided into two categories: the creation of synthetic biology tools for Xenopus and the creation of a synthetic hormonal system. We created a multi-level model of this inter-tissue communication system, concurrently laying the groundwork for modeling of synthetic genetic systems in multicellular organisms. Finally, using vertebrates in synthetic biology poses deep ethical problems, which come alongside those of animal experimentation. iGEM aims to be cool and fun, but can we or should we keep the same attitude when working with vertebrate embryos ? Should we reduce animals to objects or tools by using words such as chassis when working with these multicellular organisms? Our resident philosopher lead our team’s reflection on these issues, proposing a guide for future synthetic biologists who wish to work with Xenopus.