Team:NTU-Singapore/Project

pLaqUe Out!

The NTU iGEM '09 Team has identified atherosclerosis as the problem we would like to tackle.

Atherosclerosis is one of the major diseases affecting the world. In our research, we found the numbers were staggering, and growing. We also found that early diagnosis was rare, medications were not ideal and surgeries were a commonly used last resort.

We asked ourselves what if we could design a biological system to identify plaque sites and reduce the plaque volume in vivo?

How we did it

We set about solving the problem in a true engineering manner. This approach was systematic, and logical, because it allowed us to design a solution that catered specially to Atherosclerosis. The following are the steps we took.

• We identified the problem as plaque buildup in arteries.

• We then studied the problem site in the physiological context.
  • We listed down the disadvantages of conventional diagnosis & treatment.
  • Based on our research, we also identified key symptoms and bodily reactions to plaque buildup.

• We envisioned a solution that could identify plaque sites based on these symptoms, and specifically attack a major component of plaque, in vivo.
  • We also tried to incorporate a way to ease the diagnostic process.

• We re-cast the solution in the framework of a system, defining specific inputs & outputs to each device within the system.
  • This step allowed to objectify our goals, and visualize it in a logical algorithm-like flowchart.

• We modelled this system to see the simulated activity.
  • This allowed us to foresee bottlenecks.
  • It also identified the time scale and the rate of activity of our proposed system.

• We then identified E.Coli as a suitable organism for "building" a prototype system.
  • This step was a proof of concept.

• Logically, the next step would be to construct the actual system (in a macrophage).
  • However, due to the time constraint of the iGEM research period, we did not pursue this option.

• So, we did testing & characterization of our prototype system.
  • This step verified our constructs & validated their activity.

Atherosclerosis in physiology

Here's an informative video describing the nature of atherosclerotic buildup, and deadly consequences.

As you can see, LDL-cholesterol buildup, and subsequent foam cell formation is the root cause of plaque buildup. The condition becomes increasingly irreversible as calcification sets in. The problem then is that plaque buildup is not identified early enough for effective medication that actually reverses the condition, rather than alleviating the symptoms.

Our solution is target the early stages of plaque build-up. Our system needs to sense potential atherosclerotic sites, and immediately breakdown components of buildup as well as help in the early diagnosis.

Checklist of deliverables

Title is self-explanatory

In Context

Explain and re-iterate that this is a proof-of-concept.

References/Literature