Synthetic Biology Project Examples http://2010.igem.org/Main_Page GCAT Synthetic Biology Workshop July 8, 2010 Medicine Energy Environment Technology GCAT Synthetic Biology Workshop July 8, 2010 Medicine Synthetic Biology Offers New Hope For Malaria Victims March 24, 2004 “In a preview of things to come from the fledgling scientific field of "synthetic biology," researchers with Lawrence Berkeley National Laboratory's Physical Biosciences Division (PBD) and the University of California at Berkeley's Chemical Engineering Department are developing a simple and much less expensive means of making one of the most promising and potent of all the new antimalarial drugs.” March 4, 2004 According to the WHO, each year nearly 500 million people become infected with malaria, and nearly three million — mostly children — die from it. The leaves of Artemisia annua, the sweet wormwood tree, are the source of artemisinin. Although lethal to all known strains of malaria, the drug is produced in small quantities; extracting it from the leaves is an expensive process. Although this tree can grow in many places, it only produces artemisinin under specific agricultural and climatological conditions. China is one of the areas where artemisinin is produced, and the Chinese have been using it in the herbal medicine ginghaosu for more than 2000 years. The idea behind the Synthetic Biology Department at the Lawrence Berkeley National Laboratory’s Physical Biosciences Division is “to design and construct novel organisms and biologically-inspired systems that can solve problems natural biological systems cannot, and also provide new information about living cells.” -- PBD director Graham Fleming "By inserting genes from three separate organisms into the E. coli, we're creating a bacterial strain that can produce the artemisinin precursor, amorphadiene. We are now attempting to clone the remaining genes needed for the E. coli to produce artemisinin." -- chemical engineering professor Jay Keasling Keasling and his research group transplanted genes from yeast and from the sweet wormwood tree into the bacterium, then bypassed E. coli's metabolic pathways and engineered a new one based on a metabolic pathway in yeast. As a result of their efforts, the yield of the artemisinin precursor amorphadiene in that laboratory strain of E. coli was increased by 10,000 times. To boost production, scientists need to be able to purify chemicals from fast growing, fast producing microorganisms such as cultured yeast and bacteria. So Jay Keasling and his colleagues genetically engineered yeast to produce the proteins required for the myriad metabolic pathways required to manufacture artemisinin. A big problem was low yield. The proteins produced intermediates in the artemisinin pathway, but these intermediate chemicals would often accumulate and harm the cell. The solution was a scaffold, a physical method to link the proteins to keep them in close proximity to each other. That way, when the first protein produced an intermediate, that intermediate would be picked up by the second protein, waiting nearby, and converted into the second intermediate, and so forth, until artemisinin was produced. Energy 2008 Project by Harvard iGEM Team http://2008.igem.org/Team:Harvard Shewanella oneidensis MR-1 Four 2009 iGEM Projects http://2009.igem.org/Team:HKU-HKBU http://2009.igem.org/Team:HKU-HKBU/Assembly#Step_6._Using_the_Speed_Controller http://2009.igem.org/Team:HKU-HKBU/Assembly#Step_6._Using_the_Speed_Controller pyruvic acid------> carbon dioxide + acetaldehyde ------>ethanol http://2009.igem.org/Project#Project_1 http://2009.igem.org/Team:TzuChiU_Formosa http://2009.igem.org/Team:Wash_U http://www.youtube.com/watch?v=mbzObmQKJSo Environment Arsenic Biosensor Edinburgh iGEM 2006 Poison Water • Arsenic poisoning affects 100 million people • Serious in Bangladesh • Wells tap sedimentary layer with Arsenic • 1 in 4 wells contaminated • Testing methods expensive, require instruments and expertise Simple Design • INPUT Arsenate/Arsenite binds to arsR Repressor • Derepression of lacZ gene • Lactose metabolism causes H+ production • OUTPUT lower pH of medium Complex Design • INPUT Arsenate/Arsenite binds to ArsR Repressor •Genetic circuit used to control LacZ and Urease production • OUTPUT is low, neutral, or high pH Range of Outputs If no arsenic is present: Urease raises the pH to 9-10 If 5 ppb arsenic is present: Repressor shuts down Urease, pH remains neutral, pH 7 If 20 ppb arsenic is present: LacZ produced, pH 4.5 Project Summary Our team have designed and modelled a biosensor that can detect several different concentrations of arsenic and emit a pH signal in response. The device can detect the WHO guideline level of 10 ppb and the Bangladeshi standard of 50 ppb for arsenic in drinking water. A proof of concept Biobrick construct has shown a pH response to a concentration of arsenic of 5 ppb. Edinburgh iGEM 2006 Awards: Best Real World Application, Best Poster Technology http://parts.mit.edu/igem07/index.php/Peking Toggle Switch Toggle Switch NOR Logic Gate A B Output 0 0 1 0 1 0 1 0 0 1 1 0 Toggle Switch Best NOR gate Toggle Switch The E.ncapsulator Imperial College, 2009 Valencia, 2009