Team:Goettingen/Achievement
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+ | <b>Achievements:</b><br /> | ||
+ | <ul> | ||
+ | <li><a href="#Team:.09Goettingen">Team profile</a></li> | ||
+ | <li><a href="#Achievements">Our achievements</a></li> | ||
+ | <li><a href="#We_apply_for">We apply for:</a></li> | ||
+ | <li><a href="#About_our_parts">About our parts</a></li> | ||
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'''Project Abstract:''' | '''Project Abstract:''' | ||
- | Since the discovery of penicillin by Alexander Fleming in 1928, antibiotics have marked a major victory of mankind in the battle against infectious diseases. However, after 90 years, the antibiotics are now losing their old time glory: Bacteria acquire resistance against antibiotics and become unbridled. We must control the use of antibiotics, meanwhile, we need new antibiotics, which can sufficiently eliminate the invaders without hurting the "good" bacteria. Therefore, | + | Since the discovery of penicillin by Alexander Fleming in 1928, antibiotics have marked a major victory of mankind in the battle against infectious diseases. However, after 90 years, the antibiotics are now losing their old time glory: Bacteria acquire resistance against antibiotics and become unbridled. We must control the use of antibiotics, meanwhile, we need new antibiotics, which can sufficiently eliminate the invaders without hurting the "good" bacteria. Therefore, cyclic di-AMP, an important, recently discovered signaling molecule in Gram-positive bacteria, has come to our sight. Our project is to build a screening system targeting c-di-AMP, which could be applied in novel-drug screening. With this system, the level of c-di-AMP in the cell can be visualized and measured. |
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- | Best | + | <br /> |
+ | ===We apply for=== | ||
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+ | Best BioBrick Measurement Approach | ||
- | + | Best Model | |
- | The progress in the development of new antibiotics has been very slow during the last decades, leaving many strains of bacteria untreatable. This problem has been growing ever since the invention of antibiotics but has now become a real threat to millions of people around the world. This Threat we want to tackle with a new approach: We develop a system to test substances on a new target, | + | The progress in the development of new antibiotics has been very slow during the last decades, leaving many strains of bacteria untreatable. This problem has been growing ever since the invention of antibiotics but has now become a real threat to millions of people around the world. This Threat we want to tackle with a new approach: We develop a system to test substances on a new target, c-di-AMP. |
C-di-AMP was discovered to be an essential signaling molecule in Gram-positive bacteria including the pathogens ''Streptococcus pneumoniae, Staphylococcus aureus'' and ''Listeria monocytogenes''. Both loss and overproduction of c-di-AMP have detrimental effects on cell growth, cell wall synthesis and propagation. | C-di-AMP was discovered to be an essential signaling molecule in Gram-positive bacteria including the pathogens ''Streptococcus pneumoniae, Staphylococcus aureus'' and ''Listeria monocytogenes''. Both loss and overproduction of c-di-AMP have detrimental effects on cell growth, cell wall synthesis and propagation. | ||
- | '''Best | + | '''Best BioBrick Measurement Approach: ''' |
Thus, the diadenylate cyclase (DAC) which catalyses the condensation reaction of 2 ATP molecules to c-di-AMP is the key factor for c-di-AMP homeostasis. We are convinced that the DAC protein is a very promising target for the development of highly specific antibiotic substances which exclusively act on Gram-positive bacteria and are not harming Gram-negative ones, including the gut bacterium ''Escherichia coli'' as well as humans. We characterized the DAC ''in vivo'' and ''in vitro''. Here, we introduce a truncated but functional DAC, which localizes to the cytosol and can easily be purified. Furthermore, we obtained protein crystals and the protein structure by X-ray diffraction analysis. For the first time ever the 3D structure for this cyclase, which is conserved among all important Gram-positive bacteria, was resolved. This structure will be an important starting point for bioinformatic docking studies (BBa_K1045003) | Thus, the diadenylate cyclase (DAC) which catalyses the condensation reaction of 2 ATP molecules to c-di-AMP is the key factor for c-di-AMP homeostasis. We are convinced that the DAC protein is a very promising target for the development of highly specific antibiotic substances which exclusively act on Gram-positive bacteria and are not harming Gram-negative ones, including the gut bacterium ''Escherichia coli'' as well as humans. We characterized the DAC ''in vivo'' and ''in vitro''. Here, we introduce a truncated but functional DAC, which localizes to the cytosol and can easily be purified. Furthermore, we obtained protein crystals and the protein structure by X-ray diffraction analysis. For the first time ever the 3D structure for this cyclase, which is conserved among all important Gram-positive bacteria, was resolved. This structure will be an important starting point for bioinformatic docking studies (BBa_K1045003) | ||
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To test an antibiotic on the new target, we isolated (as mentioned above) the truncated DAC and did activity measurements on it. Using this data, we can now screen thousands of substances for impacts on the function of the DAC (''in silico'' and ''in vitro'' screening). Furthermore, we created ''in vivo'' reporter systems in ''E. coli'', giving us the ability to sense the amount of c-di-AMP inside the cells, as well as to find possible inhibitors or competitors for c-di-AMP. Last but not least, the combination of the two: An ''in vivo'' reporter system with the DAC expressed in the same cell will be the c-di-AMP pathway from Gram-positive bacteria, reconstructed in ''E. coli''. This way, it will be ready to screen for substances lethal to it´s Gram-positive relatives, without harming our host. In consequence, our model will facilitate the search for novel antibiotics hitting a novel target in Gram-positive bacteria. | To test an antibiotic on the new target, we isolated (as mentioned above) the truncated DAC and did activity measurements on it. Using this data, we can now screen thousands of substances for impacts on the function of the DAC (''in silico'' and ''in vitro'' screening). Furthermore, we created ''in vivo'' reporter systems in ''E. coli'', giving us the ability to sense the amount of c-di-AMP inside the cells, as well as to find possible inhibitors or competitors for c-di-AMP. Last but not least, the combination of the two: An ''in vivo'' reporter system with the DAC expressed in the same cell will be the c-di-AMP pathway from Gram-positive bacteria, reconstructed in ''E. coli''. This way, it will be ready to screen for substances lethal to it´s Gram-positive relatives, without harming our host. In consequence, our model will facilitate the search for novel antibiotics hitting a novel target in Gram-positive bacteria. | ||
- | ==About our parts== | + | <br /> |
+ | ===About our parts=== | ||
We have two new parts built, namely: [http://partsregistry/Part:BBa_K1045003 BBa_K1045003],[http://partsregistry/Part:BBa_K1045017 BBa_K1045017] | We have two new parts built, namely: [http://partsregistry/Part:BBa_K1045003 BBa_K1045003],[http://partsregistry/Part:BBa_K1045017 BBa_K1045017] |
Latest revision as of 19:34, 4 October 2013