Difference between revisions of "Team:Tongji Shanghai/Model"

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       <h3 class="classic-title" style="margin-top:0px"><span>Favorite Parts</span></h3>
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       <h3 class="classic-title" style="margin-top:0px"><span>Drug Concentration Forecasting in Body Tissue</span></h3>
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          <h4>Overview<span class="head-line"></span></h4><br>
 
    
 
    
 
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             <ul style="margin-left:0px; font-size:16px;">Team Fudan need tet-on or tet-of promoter to get tetO element and miniCMV as the promoter to drive their genes of interest. Vice professor Wenwen Jia in our school works on apparent heredity field, happens to have tet-on kit for his work. We made contact with Pro. Wenwen Jia and gained 3μl. <br><br>
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             <ul style="margin-left:0px; font-size:16px;">In pharmaceutical research and development,it is certainly worth making predictions of trends and variation of the drug concentration in the body tissue.
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            We also asked him for the associating kit that responses to panmycin and send the signal to promoter. Team Fudan used these two kits to PCR and continued their experiments. At the same time, Team Fudan had provided great help either. They built their kit ahead of us, and they generously provided almost all of the materials that we gonna need for kit submitting.(15 ml of chloromycetin powder,8 chloramphenicol resistance plates,80ml chloramphenicol resistance LB,Enzyme of XbaI and SpeI each 3μl) </ul>
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            We use a classical pharmacokinetic model to build a drug concentration forecasting function to describe the drug time-dependent concentration change trend, which could be a reference for pharmaceutical research.</ul>
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          <h4>Model Building<span class="head-line"></span></h4><br>
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          <ul style="margin-left:0px; font-size:16px;">I.After taking drug, the change rate of drug concentration in body can be expressed as the dynamics equations:</ul>
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          <img src="https://static.igem.org/mediawiki/2016/1/10/T--Tongji_Shanghai--form1.png">
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          <ul style="margin-left:0px; font-size:16px;">where x(t) is the drug concentration in body fluids, </ul>
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          <ul style="margin-left:0px; font-size:16px;">r01(t) is the drug absorption rate,</ul>
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          <ul style="margin-left:0px; font-size:16px;">r10(t) is the elimination rate.</ul>
 
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          <ul style="margin-left:0px; font-size:16px;">As r10(t) is proportional to the x(t), there is another formula:</ul>
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          <ul style="margin-left:0px; font-size:16px;">where k10 is the constant of elimination rate </ul>
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      <h3 class="classic-title" style="margin-top:20px"><span>Basic Parts</span></h3>
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          <h4>BBa_K1922001<span class="head-line"></span></h4><br>
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          <ul style="margin-left:0px; font-size:16px;">Approximately 80% of cancers are immortalized by constitutive activa-tion of telomerase to maintain telomeres throughout rapid cellular prolif-eration. HTert promoter is the promoter we cloned from human cell, which can drive the transcription of telomerase in human. We hoped that it can promote the transcription of the certain gene following it in tumor cells specifically, instead of in normal cells. </ul>
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           <ul style="margin-left:0px; font-size:16px;">II. According to knowledge of pharmacology, absorption rate of drug in proportion to the amount of drug that are not absorbed;the elimination rate in proportion to the drug concentration in body fluids, there is another formula:
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          <img src="https://static.igem.org/mediawiki/2016/1/14/T--Tongji_Shanghai--form3.png">
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          <ul style="margin-left:0px; font-size:16px;">F is defined as the total amount of drug.</ul>
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          <ul style="margin-left:0px; font-size:16px;">T is the total time that patients take the drug.</ul>
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          <ul style="margin-left:0px; font-size:16px;">In most cases, drug is taken at moment, T = 0</ul>
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          <ul style="margin-left:0px; font-size:16px;">After several mathematical derivation, we get the model function to describe concentration in body tissue.</ul>
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          <img src="https://static.igem.org/mediawiki/2016/e/e8/T--Tongji_Shanghai--form4.png">
 
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           <h4>BBa_K1922003<span class="head-line"></span></h4><br>
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           <h4>Experiments Verification<span class="head-line"></span></h4><br>
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          <ul style="margin-left:0px; font-size:16px;">The cells of all tissues react to various stresses through the quick synthesization of HSPs.As the most important HSPs family. HSP70 has the highest temperature sensitivity and conservation. Having synthesized human hsp70 promoter, we hope it can drive the transcription of selected gene after heat shock at certain tem-perature. From the literature we finally set the preform condition as 42C for 1h </ul>        
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          <ul style="margin-left:0px; font-size:16px;">We used a set of experiment data to conduct verification of our model. </ul>
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          <ul style="margin-left:0px; font-size:16px;">We measured the drug concentration, after patients take 3g drug sample. And we get the drug concentration change trend in a few hours.</ul>
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          <img src="https://static.igem.org/mediawiki/2016/e/ee/T--Tongji_Shanghai--form5.png">
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          <img src="https://static.igem.org/mediawiki/2016/1/18/T--Tongji_Shanghai--form7.png">
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          <ul style="margin-left:0px; font-size:16px;">Based the experiment data, we use a classical non-linear model to build a differential equation and solve it, estimating the return model parameter from the experimental data by ordinary least squares method. </ul>
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          <img src="https://static.igem.org/mediawiki/2016/9/97/T--Tongji_Shanghai--form6.png">
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          <ul style="margin-left:0px; font-size:16px;">Comparing experiment data and model fitted data, we find the model are in good agreement with experiments results.</ul>
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          <h4>Discussion<span class="head-line"></span></h4><br>
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          <ul style="margin-left:0px; font-size:16px;">It's necessary to monitorl the variation of drug concentration in Body Tissue</ul>
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          <ul style="margin-left:0px; font-size:16px;">Based on medical dynamics theory, we build a mathematical model to describe the drug time-dependent concentration change trend. Using this model, we can determine the drug concentration in blood from mathematical theory for various kinds of drug and different conditions. We use our experiments results to verify our model accuracy, and we find the model forecasting results are in good agreement with experiments results. </ul>
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          <ul style="margin-left:0px; font-size:16px;">We believe our mathematic model, which gives a description of drug concentration change in body tissue, is able to be biological universal and reasonable for many cases. Due to the universal advantage of our model, this model can be regarded as one analysis reference for the drug metabolism research, moreover, medicinal development and clinical applications.</ul>
 
            
 
            
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Revision as of 15:32, 19 October 2016

Tongji_Shanghai-2016.igem.org Tongji Shanghai

Achievment

Why we deserve a medal.

Drug Concentration Forecasting in Body Tissue

Overview


    In pharmaceutical research and development,it is certainly worth making predictions of trends and variation of the drug concentration in the body tissue. We use a classical pharmacokinetic model to build a drug concentration forecasting function to describe the drug time-dependent concentration change trend, which could be a reference for pharmaceutical research.

Model Building


    I.After taking drug, the change rate of drug concentration in body can be expressed as the dynamics equations:

    where x(t) is the drug concentration in body fluids,
    r01(t) is the drug absorption rate,
    r10(t) is the elimination rate.

    As r10(t) is proportional to the x(t), there is another formula:
    where k10 is the constant of elimination rate

    II. According to knowledge of pharmacology, absorption rate of drug in proportion to the amount of drug that are not absorbed;the elimination rate in proportion to the drug concentration in body fluids, there is another formula:
    F is defined as the total amount of drug.
    T is the total time that patients take the drug.
    In most cases, drug is taken at moment, T = 0
    After several mathematical derivation, we get the model function to describe concentration in body tissue.

Experiments Verification


    We used a set of experiment data to conduct verification of our model.
    We measured the drug concentration, after patients take 3g drug sample. And we get the drug concentration change trend in a few hours.
    Based the experiment data, we use a classical non-linear model to build a differential equation and solve it, estimating the return model parameter from the experimental data by ordinary least squares method.
    Comparing experiment data and model fitted data, we find the model are in good agreement with experiments results.

Discussion


    It's necessary to monitorl the variation of drug concentration in Body Tissue
    Based on medical dynamics theory, we build a mathematical model to describe the drug time-dependent concentration change trend. Using this model, we can determine the drug concentration in blood from mathematical theory for various kinds of drug and different conditions. We use our experiments results to verify our model accuracy, and we find the model forecasting results are in good agreement with experiments results.
    We believe our mathematic model, which gives a description of drug concentration change in body tissue, is able to be biological universal and reasonable for many cases. Due to the universal advantage of our model, this model can be regarded as one analysis reference for the drug metabolism research, moreover, medicinal development and clinical applications.

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