The work, led by chemical biologist Dr Jason Micklefield in collaboration with geneticist Professor Colin Smith, is published online (Wednesday 5 December 2007) and will appear in next issue of the Journal of the American Chemical Societying funding from the UK ™s Biotechnology and Biological Sciences Research Council (BBSRC), scientists working in The School of Chemistry and the Manchester Interdisciplinary Biocentre have paved the way for the development of new types of antibiotics capable of fighting increasingly resistant bacteria.Micklefield, Smith and colleagues were the first to engineer the biosynthesis of lipopeptide antibiotics of this class back in 2002. They have now developed methodologies for altering the structure of these antibiotics, such as mutating, adding and deleting components.This innovation provides access to thousands of lipopeptide variants that cannot be produced easily in any other way.Dr Micklefield said: The results from this work are essential in the development of the next generation of lipopeptide antibiotics, which are critical to combat emerging super bugs that have acquired resistance to other antibiotics.The potent activity of this class of antibiotics against pathogens that are resistant to all current antibiotic treatments makes them one of the most important groups of antibiotics available. Our work relies on interdisciplinary chemical-biology, spanning chemistry through to molecular genetics. It follows the tradition of pioneering work in natural product biosynthesis and engineering that has come out of the UK.Scientists in Manchester have been doing work on calcium dependant antibiotics (CDA), which belong to the same family of acidic lipopeptides as daptomycin.In 2003 daptomycin became the first new structural class of natural antibiotic to reach hospitals in more than 30 years.But researchers say there is already evidence that bacteria are evolving and becoming resistant to daptomycin “ leading to the emergence of dangerous new super bugs.Dr Micklefield added: If we are to successfully fight and control potent new super bugs in the future, we need to be developing the next generation of antibiotics now.The research carried out by Dr Mickelfield and his colleagues is part of a larger 650,000 project called Combinatorial biosynthesis of lipopeptide antibiotics ™, which is funded by the BBSRC and supported by drug discovery company Biotica. It is concerned with elucidating and engineering biosynthetic pathways leading to complex nonribosomal lipopeptide antibiotics.

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"During this critical period, the olfactory system is flexible enough to calibrate its genetic map to its local environment," says first author Silke Sachse, a former postdoc in the Vosshall lab who is now a group leader in optical imaging at the Max Planck Institute for Chemical Ecology in Jena, Germany. "But once that window closes, the circuit is no longer plastic."

To figure out the mechanism by which the glomerulus increases its volume, the Vosshall group imaged the three types of neurons that make up the glomerulus -- olfactory sensory neurons, projection neurons and interneurons -- to see whether their structure or function had changed. The olfactory sensory neurons, which report sensory information to glomeruli, did not show any sign of structural or functional changes. However, the projection neurons, which send information from the glomeruli to the brain, and the interneurons, which communicate with the two types of neurons as well as the glomeruli, showed significant functional changes. "Usually the sensory neurons collect information and send it to the brain and it is the job of the brain to interpret what the information means," says Vosshall. "For plasticity to be useful, it probably makes sense to delegate that job to the brain rather than to the external sensory neurons."

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