Team:ATOMS-Turkiye/asoMain

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  • Tissue hypoxia, or ischemia, is the condition that describes the poor conveyance of oxygen and other vital products to body tissues and organs which consequently results tissue death.
  • Up to now,the number one cause of death worldwide is caused by ischemia and related conditions such as heart attack or stroke. Additionally, due to the remarkable damage to tissues, these diseases end up with high morbidity rates. From pharmacology to biomedical industry, variety of prevention and treatment options have been suggested, many of them have still being applied. Nevertheless, we still have not reached the very end of cure and more novel approaches from different fields may play great role for this reason. One of these approaches is, of course, synthetic biology. The benefits of SynBio allow us to manipulate micro and nano scales of cell environment in order to involve in when the action starts and to interfere at the right time. Ischemic damage is related with two different phenomena. First, the vital blood supply that carry oxygen, energy gathering nutrition and other minerals is cut down by an external effect, mostly by a clot. Afterwards, cells become unable to produce enough energy and start wasting their deployed nutrition in a different reaction cascade that results with building up toxic chemicals in the media. If the clot barrier is removed, excessive oxygen presence in the media may enhance this toxic production because of high metabolic rate of the cells. These toxic products, also known as reactive oxygen species (ROS), may increase the cell damage further. Thus, it is needed to regard the big picture of the condition In order to solve the problem. In our project, our will is to build two different devices, which work synergistically, to fix these two distinct situations. To do this, we aim to design hypoxia inducible systems, which is the first step for constructing a sensitive and robust device. Hypoxia inducible promoters and their regulator proteins are responsible for this critical mission. Beside of this, we also want to prevent the damage caused by reperfusion of blood to the hypoxic environment, we also need an additional sensitive receptor construct. After our researches, we decided to use reactive oxygen species (ROS) sensitive promoter systems. These two receptors will hopefully regulate the release of clot dissolving factors synthesized by our engineered vessel cells. Moreover, we hope to maximize the reduction of ROS damage to the cells by producing antioxidant enzymes to degrade ROS within the cells. By re-providing vital oxygen support via bloodstream and enhancing the degradation of ROS in the tissue, this project intends to propose a new treatment approach for ischemia related diseases. In the future, following the advancements in gene therapy and cell therapy industries, we would like to implement our system in living models. Especially, tissue engineered heart vessel cells or manipulating the whole body by gene containing exosomes, this treatment option may also pose an alternative prevention method for ischemic heart attack or strokes. We hope to bring encouraging results in vitro to pave the way of this promising system into the lifesaving remedy method.

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