Line 327: | Line 327: | ||
<h4>Background</h4> | <h4>Background</h4> | ||
<div class="row"> | <div class="row"> | ||
− | <div class="col-sm-8 | + | <div class="col-sm-8"> |
<div class="col-sm-12" style="border:1px solid black"> | <div class="col-sm-12" style="border:1px solid black"> | ||
<p>There are four ways to measure cataract severity (how blurred the lens is): | <p>There are four ways to measure cataract severity (how blurred the lens is): | ||
− | <ol style="font:Lato 16px"> | + | <ol style="font:Lato 16px !important"> |
<li>Lens Optical Cataract Scale III (LOCS) - a scale from 0-6 used by physicians.</li> | <li>Lens Optical Cataract Scale III (LOCS) - a scale from 0-6 used by physicians.</li> | ||
<li>Opacity (%) - used to calculate the LOC scale</li> | <li>Opacity (%) - used to calculate the LOC scale</li> | ||
Line 345: | Line 345: | ||
<div class="col-sm-4" style="background-color:lightpink;margin:0px"> | <div class="col-sm-4" style="background-color:lightpink;margin:0px"> | ||
<div class="col-sm-12" style="border:1px solid black"> | <div class="col-sm-12" style="border:1px solid black"> | ||
− | <h3>LOCS Scale</h3><br> <br> <br><br> <br> <br> | + | <h3>LOCS Scale</h3><br> <br> <br><br> <br> <br> <br><br><br><br> |
</div> | </div> | ||
</div> | </div> | ||
Line 358: | Line 358: | ||
<h4>Assumptions</h4> | <h4>Assumptions</h4> | ||
<p> | <p> | ||
− | <ol style="font:Lato 16px"> | + | <ol style="font:Lato 16px !important"> |
<li>Definition of crystallin damage: Crystallin damage is proportional to the concentration of hydrogen peroxide, and the time of exposure. This is a valid assumption, supported by the fact that the reaction between cysteine (molecules on crystallin) and hydrogen peroxide is linear. </li> | <li>Definition of crystallin damage: Crystallin damage is proportional to the concentration of hydrogen peroxide, and the time of exposure. This is a valid assumption, supported by the fact that the reaction between cysteine (molecules on crystallin) and hydrogen peroxide is linear. </li> | ||
<li>We assume that the amount of crystallin is far greater than the amount oxidized. Our product is meant for long-term cataract prevention and minor treatment, and is not suggested for patients with extremely severe cataracts. </li> | <li>We assume that the amount of crystallin is far greater than the amount oxidized. Our product is meant for long-term cataract prevention and minor treatment, and is not suggested for patients with extremely severe cataracts. </li> |
Revision as of 12:43, 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