Small molecule mediated scaffolds based on the T14-3-3 protein
Nine students from Eindhoven University of Technology formed a team to participate in the iGEM competition for the 5th year in a row. These students from the majors Biomedical Engineering and Medical Sciences and Technology faced the challenge of keeping the reputation of TU Eindhoven high, after the successes that have been achieved by the previous iGEM teams.
Over 300 teams participated in the competition this year, bringing together students from 41 different countries! Among these teams, 19 undergraduate teams participated in the New Application track including the iGEM team from TU Eindhoven. From the 27th of October until the 31st of October the team presented their work during the Giant Jamboree in Boston, Massachusetts.
This year’s team used T14-3-3 scaffold proteins, as a base to control protein-protein interactions (PPIs) with the help of small molecule regulation. By creating a universal scaffold, not only one specific PPI can be controlled, but diverse PPIs can be controlled. In this way, they hope to contribute to the ability to regulate cell processes. They for example want to implement a kill switch with the help of their scaffold in T-cells, which can be used to make T-cell Therapy safer. Their scaffold could also be used to regulate the activity of CRISPR/Cas9, which is a tool that can be used to edit the genome. For more information on their project and the results they obtained in the lab, please take a look at their website: http://2016.igem.org/Team:TU-Eindhoven
With their project, they managed to obtain a gold medal and three nominations. These nominations were in the following categories: Best New Application Project, Best Model, and Best New Basic Part. The competition was fierce and therefore they unfortunately were not able to bring home an award. They did however accomplish a lot with their research, and their findings will be used for further research by PhD students in the department Chemical Biology, here at Eindhoven University of Technology.
COMBs, Clickable Outer Membrane Biosensors
For the fourth time, a team from TU Eindhoven and ICMS participates in the international Genetically Engineered Machine (iGEM) competition, the premiere student competition in synthetic biology. This year 280 teams from 36 different countries from all over the world participate in the iGEM competition. Teams employ synthetic biological techniques to modify cells into machines to encounter real-world problems. From September 24 till September 28, 2015 the Giant Jamboree of the iGEM competition will take place in the Hynes Convention Center in Boston. Here, every team will present the project they have been working on.
Eleven TU/e students from both the master and bachelor program Biomedical Engineering have been working on the project for the last 8 months. In December 2014, the team started on brainstorming and designing the project. IGEM explores many different aspects within the field of synthetic biology: experimental work, policy and practices and model-based engineering. These are all different aspects that the team has to focus on. Therefore this multidisciplinary competition offers students the opportunity to gain more knowledge and develop their scientific skills.
Accurate and early diagnosis of diseases is at the forefront of the medical sciences. Although many biosensors have already become available, a universal biosensor platform is lacking. As a first step towards such a platform, we are introducing a transmembrane biosensor which may in the future be incorporated into signaling pathways. The biosensor is made using the basic principle of Click Coli, the project of team TU Eindhoven 2014 (2014.igem.org/Team:TU_Eindhoven).The system is characterized by three modules, aptamers as recognition elements, outer membrane proteins as the scaffold and signaling components which can translate ligand binding into a measurable signal through heterodimerization. Aptamers can be clicked onto the outer membrane proteins post-translationally using SPAAC click-chemistry, making the system inherently modular. The biosensors can be employed in a wide range of applications: from detecting biomarkers to the overuse of pesticides. We believe that in the future, the system can go beyond its function as a biosensor and may be able to trigger cellular responses.
For more information, take a look at our website: http://2015.igem.org/Team:TU_Eindhoven
A fundamental problem in utilizing genetically modified bacteria is their limited ability to survive in non-natural environments, such as the harsh conditions in industrial reactors or due to the immune system also in the human body. We report a “Plug-and-Play” system that allows the introduction of chemical anchors on cell membranes, that are subsequently used to attach a functional coating. The anchors consist of azidophenylalanine, which couples covalently with molecules containing the strained alkyne DBCO in a so-called "click" reaction. We obtained proof-of-concept that our Clickable Outer Membrane Proteins (COMP) enable this fast and effective click reaction. We applied it to create a safe “clicked-on” coating that allows E.coli to be used in the human body for healthcare purposes. Furthermore, we have designed microfluidic devices that give increased control over the click reaction and single cell coating. We believe our “Plug-and-Play” system is a versatile tool that provides numerous possibilities for engineering the outer membranes of bacteria.
Check the Click Coli wiki page:
Our project presents an alternative solution to the use of heavy metals in MRI contrast agents. The most commonly used heavy metal, gadolinium, may be involved in the induction of diseases and may be toxic if the patient has kidney failures. There is an alternative. Within CEST imaging, proteins enclosing exchangeable hydrogen atoms can generate high quality images. Escherichia coli are used to express CEST proteins when the bacteria sense a hypoxic environment via a promoter designed for this purpose. Thus, the bacteria works as both a production and delivery system for the CEST MRI contrast agent. A rapidly evolving research area in the field of oncology is focused on bacterial based cancer therapies, in which bacteria like E. Coli and Salmonella are used to induce cancer cell death. Based on this type of cancer therapy, and considering that hypoxic regions are related to tumors, our eventual goal is to use this system to target and image tumors in humans by injecting the bacteria into the bloodstream. A secondary application is the tracking of bacteria in bacterial infection studies. For iGEM, the proteins were expressed ex-vivo in both aerobic and anaerobic conditions.
Check the MRIGEM wiki page:
The ICMS participated at the 9th iGEM competition
10 TU/e students from the fields of Biomedical Engineering, Mechanical Engineering and Chemistry successfully competed in the International Genetically Engineered Machine Competition (iGEM). On October 6, 2012 they were awarded the silver medal at the Regional Jamboree for their project on the development of a Light Emitting Cell Display.
iGEM is a yearly competition in the field of synthetic biology for undergraduate students which starts around March. The competition was first held in 2004 and since then it has grown from the initial 5 competing teams into an international competition in which 194 teams take part. In October the teams representing each of the 5 different continents, with Europe as the second biggest represented continent after Asia, participated at their Regional Jamboree to present their work, with the aim of advancing to the World Championship. Finally in November the World Championship Jamboree will be held in Cambridge, Massachusetts, where the advanced teams of the different continents will compete to become the ‘Grand Prize Winner’.
iGEM is about the use and production of standardized biological parts for designing and building biological systems which should ultimately be operated inside a living cell. The philosophy behind this scheme is that every year teams contribute their new and modified parts back to the so called Registry of Biological Parts where they can be shared more easily with future teams, giving a more effective route for progress. However, iGEM is not only about designing and building these new systems; it is also important to support these systems with a good working mathematical model and show that the project is publicly relevant. When going through this process collaborations will prove to be essential and doing so will be highly rewarded; because this really reflects the iGEM spirit.
Since the competition has a high multidisciplinary content the ICMS supports this endeavor and as an integrated part of the TU/e Advanced Study Centre they assembled a team of highly motivated students from various fields to compete for the first time in this competition.
The team was assembled in December 2011 and they started in January by writing their project proposal. Over the following few months they converged on their final idea: the construction of a ‘Light emitting Cell Display’ by using ‘Super Optimized Modified Yeast’ as a basis, or SOMY-LCD for short. Finally during the summer holiday they went to the laboratory where they constructed their envisioned biological system and they prepared themselves for the first part of this two-tiered competition. In October they presented their final work at the Regional Jamboree, held at the Vrije University, after which they received the Silver Medal for their work. The highlight of this final day was the following comment posted live from the audience: “In summary the presentation was very good. The use of multimedia suited well with the project and the presentation covered all topics one would expect from a top iGEM team. If you missed this one: make sure you watch this one, as soon as it is posted online!”.
For more information please visit: http://2012.igem.org/Team:TU-Eindhoven and http://www.synthetischebiologie.nl/2012/10/tu-eindhoven/.