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+ | <li>In the first part, we find how the absorbance measurements in the lab are related to the severity of the cataracts. Through literature data, we can relate LOCS to the opacity of the lens. Then, via physical calculations, we can relate the opacity of the lens to the absorbance of the lens at 400 nm.</li> | ||
+ | <li>Then, we use our team’s experimental data in the cataract model. For each trial, the concentration of H2O2 and the length of exposure are given, so we can calculate the theoretical crystallin damage using the definition above and the assumptions we made. In each trial we also measured the absorbance, so we have a relation between crystallin damage and absorbance. </li> | ||
+ | <li>However, we need to make a minor adjustment, because absorbance is affected by dilution. When the fish lens was isolated, they were placed in Tris buffer and diluted. We calculate the ratio of volumes from diluted volume to the Tris buffer, and multiply each absorbance measurement by this value.</li> | ||
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+ | <h3>LOCS Scale</h3><br> <br> <br><br> <br> <br> <br><br><br><br> | ||
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Revision as of 15:27, 17 September 2016
Modeling
Overall Modeling Abstract
Abstract
Our goal is simple: produce GSR/25HC, package it into nanoparticles, and transport into the lens. GSR/25HC is released over time, which decreases H2O2 concentration, reduces crystallin damage, and prevents cataracts. Our models approach these steps in reverse order, starting with our desired goal, and working backwards to understand the entire process.
Achievements
- Bridged the gap between the medical, biological, and chemical measurement of crystallin damage.
- Predicted impact of adding GSR and 25HC on the amount of crystallin damage in the lens.
- Created Nanoparticle Customizer for user to find a full treatment plan.
- Generalized Customizer to allow other iGEM teams to predict any nanoparticle drug delivery
- Analyzed sensitivity of prototype, and suggested insights into optimal manufacturing of prototype.
- Experimental data used to develop Models 1 and 3.
Outline
Introduction
Why Model?
In the lab, biologists are often unable to test everything experimentally. For example, in our cataracts project, cataract prevention occurs in the long-term, from 20-50 years. Obviously, although short experiments can provide us an idea of what prevention may look like, the power of computational biology allows us to model into the future. As a result, our modeling has been crucial in developing a prototype.
Focus
Most iGEM teams perform modeling on gene expression, which we accomplish in model 5. However, as our construct is not directly placed into the eyes, how our synthesized protein impacts the eyes after it is seperately transported is much more interesting. As a result, we spent the majority of our models on understanding the impacts on the eye.
Guiding Questions
- How much GSR do we want inside the lens?
- How do we use nanoparticles to control the amount of GSR in the lens?
- How do we synthesize GSR, package into NP, and send it into the eye?
Model 1: Crystallin Damage
Abstract
In our experiments, absorbance measurements are meaningless without understanding how severe a cataract that absorbance measurement means. We use literature research to relate LOCS, the physician's scale of cataract severity) to absorbance, which is how we quantified crystallin damage in experiments. We use experimental data to understand how crystallin damage can be quantified by measuring absorbance. With this model, we can calculate how much crystallin damage we have to limit to reduce LOCS to an acceptable level.
Purpose
How much do we need to limit crystallin damage so surgery is not needed?
Conclusion
To make sure LOCS rating remains under 2.5, which has equivalent absorbance value of 0.108 a.u, we must add enough GSR to decrease crystallin damage until it is below 1.941 M-h.
To make sure LOCS rating remains under 1.0, which has equivalent absorbance value of 0.0299 a.u., we must add enough GSR to decrease crystallin damage until it is below 1.220 M-h.
Model 2: GSR/H2O2
Abstract
Abstract
Purpose
Purpose
Conclusion
Conclusion
Model 3: Nanoparticles
Abstract
Abstract
Purpose
Purpose
Conclusion
Conclusion
Model 4: Eyedrops
Abstract
Abstract
Purpose
Purpose
Conclusion
Conclusion
Conclusion
Yay