Health and Synthetic Biology IX
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
Parasites and yeast
Besides team Imperial College 2010, team École Polytechnique Fédérale de Lausanne also came up with a proyect that aimed to help treatment against a parasite.
The project of the swiss team consisted of generating useful BioBricks to fight malaria parasite, Plasmodium falciparum, which would be expressed in a bacterial chassis (Asaia spp.); these kind of bacteria, symbionts of the mosquito’s gut, would produce anti-malaria BioBricks inside Anopheles mosquito (which are the vehicles through which P. falciparum and other plasmodia reach their final host). This way, P. falciparum cells would find a hostile environment inside their main vehicle and its reproduction rate would decrease to levels that may prevent its transmission to humans.
Finally, concerning the use of yeast as chassis, team Virginia 2011 conceived a producer of VEGF (Vascular Endothelial Growth Factor) and PDGF (Platelet-derived Growth Factor); this system would accelerate wound tissue regeneration.
and mammalian cells chassis
Synthetic Biology (SynBio) applications in healthcare go beyond treatment of bacterial and parasite infections. In the iGEM competition, young student teams from all around the world have conceived novel ways to apply SynBio concepts to contribute to improve gene therapy, non-infectious diseases treatment (i.e. metabolic or autoimmune disorders) and to the introduction of mammalian cells chassis as tools to develop new technologies.
In 2009, team of Tsinghua University came up with a system of chimeric vectors, which would have the structure of lambda phage, but would display also some adenovirus proteins; these vectors would carry therapeutic DNA to human cells.
Team Freiburg-Bioware 2009 adapted some of the components of the human adeno-associated virus and created a BioBrick kit with them to facilitate assembly of these kind of vectors.
Finally, in 2011 team of University College London conceived a vector system based on super-coiled DNA: overexpressing a DNA gyrase enzyme in an E. coli chassis, the production of super-coiled DNA -which would contain therapeutic genes- would be increased, creating a highly-efficient production system.
Atherosclerosis is a disorder whose treatment has been approached by teams NTU Singapore 2009 and Queens 2009. Team Singapore came up with a system based in a chassis of T-cells that could sensate damaged areas in the circulatory system, degrade cholesterol and expand blood vessels, besides of generating a fluorescent signal useful to sense the evolution of the system.
On the other hand, the canadian team conceived a system based in an E. coli chassis that would synthesize and express in its surface a fragment of VLA-4 receptor, which recognizes damaged endothelium; when cells gathered in damaged areas, they would produce a quorum sensing signal and generate biological effectors; finally, a self-destruction mechanism would eliminate bacteria before they caused any troubles to the host.
Team SJTU-BioX-Shanghai 2010 focused in treatment for osteoarthritis. The team designed two systems -an eukaryotic one and a prokaryotic one- that, in a few words, detected hypertrophic chondrocytes -typical of arthritic articulations- and helped decrease the amount of hypertrophic chondrocytes through inducing its dedifferentiation.
Team Stockholm 2010} came up with a bacterial chassis capable of producing membrane penetrating peptides with possible applications on vitiligo.
Finally, team Stanford 2009 conceived a system to treat intestinal inflammatory disease in a probiotic E. coli chassis that would regulate differentiation of T CD4 cells through the synthesis of retinoic acid or interleukin-6.
The usefulness of mammalian cells as experimental models has attracted some teams to focus their efforts in the development of these kind of chassis.
Team Purdue 2009 came up with a chassis of microglial cells, which work as a seek and destroy mechanism, with possible applications to remove CD133+ cells (from glioblastome) and, in principle, to other kinds of cells.
Finally, team University of California at San Francisco 2010 designed a series of systems to improve performance of immune killer cells (Cytotoxic T-cells and Natural Killer cells): 1) increasing its precision with a genetic circuit that works as a logic gate ANDN, 2) increase the power of the signal cascade induced by the contact with an antigen when including a synthetic GPCR, and 3) use of peptide tags to target toxic proteins to killer cells’ granules.