Health and Synthetic Biology - VII
Translation by P. Quintero
Health and Synthetic Biology I - Tackling infections - Bacteriophages and Quorum sensing vs cholera
Health and Synthetic Biology II - Vaccines and drugs - Vaccines
Health and Synthetic Biology III - Vaccines and drugs - Discovering new drugs
Health and Synthetic Biology IV - Vaccines and drugs - Expanding the genetic code
Health and Synthetic Biology V - Vaccines and drugs -Metabolic engineering
Health and Synthetic Biology VI - Health and iGEM - Bacteria, parasites and yeasts I
Health and Synthetic Biology VII - Health and iGEM - Bacteria, parasites and yeasts II
Health and Synthetic Biology VIII - Health and iGEM - Bacteria, parasites and yeasts III
Health and Synthetic Biology IX - Health and iGEM - Bacteria, parasites and yeasts IV and Gene therapy, non-infectious diseases and mammalian cells chassis
Health and iGEM
Bacteria, parasites and yeast
Biological-effector producers.- Among producers of a single kind of biological effectors, one of the most interesting iGEM projects is that of Washington University 2010, which deals with mechanisms with antibiotic activity. The team came up with an antibiotic mechanism to fight Gram (+) bacteria, specifically targeting Bacillus anthracis (the pathogen that causes anthrax), based on the removal of the pathogen’s protective coating through the CapD protein. The project consisted on an E. coli chassis expressing a variant of the CapD protein designed by the team itself using FoldIt; this variant, called CapD_CP, presented a poly-glutamate hydrolase activity higher than the wild type.
In 2011, the team Washington University used FoldIt to identify potential mutable sites that could increase the activity of a gluten-degrading enzyme, with the purpose of producing it at large-scale, encapsulating it and using it as therapeutic agent against gluten intolerance. Remarkably, the team was able to create an enzyme with an activity 700-fold higher than the wild-type.
The second type of biological-effector bacterial systems are composed systems, that is to say, based on the expression of more than one kind of effector.
Among these one of the most outstanding projects was also developed by team Washington University 2010. Using an E. coli chassis, the team came up with a system to kill Gram (-) bacteria based on the injection of Tse2 toxin -from Pseudomonas aeruginosa- through secretion system type IV also from P. aeruginosa. Briefly, in response to quorum sensing signals of a Gram (-) bacteria, E. coli will synthesize the toxin along with its respective antitoxin (to protect itself) and finally inject it into the Gram (-) bacteria.
The team from Imperial College 2009 conceived a mechanism to target peptides to the intestine using an E. coli chassis, that will synthesize the peptide of interest, build a colanic acid capsule to protect itself from freeze drying through synthesizing trehalose, and finally degrade its own genome when inducing the expression of a restriction enzyme. This way, they designed a whole producing line from the peptide synthesis to its encapsulation in a resistant and safe vector (as genome degradation will prevent its reproduction and possible infection). This protection concept involving colanic acid to target peptides to the intestine was as well developed by Wisconsin-Madison 2010, along with three different circuits to induce lysis in response to signals present in the intestine -pH and bile- aiming to release the desired molecules.
Team UNICAMP-EMSE Brazil 2011 came up with a mechanism to counteract the effects induced by stress during differentiation of T-CD4 lymphocytes. The system consisted on an E. coli chassis capable of sensing cathecolamines -which are related to stress response- and produce IL-12 in response to them; synthesis of IL-12 will restore the balance between Th-1 and Th-2 lymphocytes, preventing the organisms to become bound to microbial attacks. Finally, due to IL-12 also stimulates a NO-mediated inflammatory response, the team came up with a mechanism to sens NO and produce IL-10, an effector with anti-inflammatory activity.
Probiotics.- A probiotic organism is the one that brings a health benefit when consumed; these benefits have been increased and diversified with ideas of some iGEM teams.
Team MIT 2008 developed a chassis of Lactobacillus bulgaricus capable of protecting teeth through the expression of a peptide that prevents colonization by Streptococcus mutans. Being so,the protector agent can be targeted to teeth simply through yogurt.
Last but not least, also using a Lactobacillus chassis, uOttawa 2009 conceived a mechanism to synthesize cellulose; this way, part of consumed glucose would be transformed into cellulose and not digested, which can be helpful to control weight-gain.