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From 2011.igem.org

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We're engineering a genetic circuit in yeast to accelerate human wound-healing with the goal of preventing dangerous infection which is often exacerbated in chronic or slow-healing wounds. We hope to accomplish this by locally expressing a set of growth factors associated with accelerated healing in a time-dependent fashion by microorganisms at the wound site.

Wound contamination is a double-edged sword. Virtually all wounds (~98%) are contaminated by aerobic organisms such as yeast and bacteria. The vast majority of these are benign, and many species actually aid the wound-healing process. On the other hand, the longer a wound remains unhealed, the greater the probability of dangerous infection by harmful pathogens. These dangerous infections can cause serious illness and even be life-threatening. In other words, microorganisms living at a wound-site are not necessarily bad, and often do good insofar as they accelerate the healing process or prevent serious infection.

The wound-healing process itself is a very complicated set of interdependent processes, but one bottleneck that can be alleviated is angiogenesis, the re-growth of vasculature. This can be accelerated by sequentially expressing vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) in a time-dependent fashion in response to hypoxia-inducible factor (HIF-1). When expressed locally at appropriate levels, this has the potential to appreciably accelerate rates of wound-healing with few side-effects. The challenge is to design a genetic circuit that achieves optimal rates of HIF-linked growth factor expression without over-shooting target expression because over-expression of VEGF can have very serious side-effects.

Of the possible host organisms (yeast and bacteria), yeast are better suited to this application because they possess the complicated biomolecular machinery required to assemble the complex mammalian growth factors in question. Further, yeast have a much more manageable doubling time than bacteria, significantly reducing the risk of out-of-control proliferation in a clinical setting.

We are in currently in the process of assembling our constructs from overlapping single-stranded oligos synthesized off-site and expressing them in yeast using a standard vector plasmid.