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Team:Uppsala University
From 2012.igem.org
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Project descriptionTeam Uppsala University 2012 is dedicated to combating the rising antibiotic resistance in bacteria by means of synthetic biology. Old and well-known antibiotics are quickly becoming ineffective as resistance genes are spreading. Scientist around the world struggle with varying success to develop new antibacterial substances. But do we really have to abandon classic antibiotics? Team Uppsala University begs to differ, we believe new methods will allow us to combat the resistance itself, and make the bacteria once again sensitive to old drugs. Working with real-world resistance genes isolated from ESBL outbreaks at Swedish hospitals, we are developing anti-resistance systems active at three different levels: DNA level, transcriptional level and translational level. Our systems will be delivered to the target bacteria using an engineered phage and/or a conjugative plasmid. At DNA level, we will develop a method for permanent removal of plasmids from bacteria. Using TAL Effector Nucleases, we will be able to target and cut individual resistance genes. At transcriptional level, we will use synthetic super-repressors to repress transcription of resistance genes and native defense mechanisms in bacteria. At translational level, we will construct a modular large-scale screening system for sRNA:s and use it to find strongly silencing RNA sequences against three common resistance genes. With this team on the project, there is no question about it: Resistance is futile! |
Achivements
SmallRNA working!
Constructed smallRNA downregulating antibiotic resistance Improved existing part Improved standard plasmid backbones from the 4 series. Cool new biobricks Made several biobricks and new applications for them, demonstrated how they worked and characterized them. Helped other teams. By sending several of oour constructed biobrick parts to other teams. Characterization of promotors Measured several different promotors to gain better understand of promotor choice. |
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Silencing sRNAWe have developed a modular screening system and protocol for finding silencing sRNA:s against arbitrary genes. Using this, we have found a strongly silencing sRNA:s against a clinical antibiotic gene and lowered the minimary inhibatory concentration five-fold in resistant bacteria. |
New BackbonesWe have constructed a range of new standard low copy backbones, and variants with built-in lacIq repression for tight control of toxic genes, thermosensitivity and FRT sites for removing resistance cassettes. This work was induced as it turned out that the common registry pSB4 backbones all have a faulty copy number regulation, while we needed low copy backbones for out project. |
ChromoproteinsProteins with an visible intrinsic color are the simplest possible reporters i molecular biology. Most iGEM:ers are familiar with the Red Flourescent Protein (RFP), but there are many other colors aviable among all organism of the world. We have characterized and submitted new chromoproteins, allowing multiplexed colorful reporters. |
