Difference between revisions of "Team:TP-CC San Diego/Model"

 
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<h3 class = "day"> CRISPR/Cas9 System </h3>
 
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Cancer is a type of genetic disease which results in an uncontrollable growth of cells; while some cancers are benign, a large number of them are malignant and can lead to death. A large proportion of human cancer is caused by the acquisition of somatic mutations across an individual's lifetime, while germline mutations inherited from parental germ cells contribute to another a small, but significant part. Though contemporary treatment methods, including radiation therapy and cytotoxic chemotherapy, have achieved substantially, they often cause severe side effects. These include fatigue, infection, numbness, nausea, and pain, due to their lack of specificity.
 
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Over the past decade, comprehensive sequencing studies have revealed the genomic landscapes and identified important oncogenic drivers of human cancer. These efforts led to the development of cancer-specific targeted therapy, a way to improve therapeutic efficiency and overcome unsatisfying side effects. Imatinib, a chemotherapy medication which specifically targets BCR-ABL protein, is one of the successful examples for chronic myeloid leukemia treatment. In fact, patients who received imatinib have an overall survival rate of 85%. However, for certain types of cancer, targeted therapy has not shown promising results, with a response rate lower than 10%. Development of novel therapeutic strategy is still urgently needed. <br/> <br/>
 
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Oncogene amplification is one of the most common events in cancer genome and is a frequent driving force behind cancer cell behavior. Before scientists confirmed that human somatic cells carry 46 chromosomes, abnormal chromosome numbers in cancer cell was noticed, termed aneuploidy. With the increase in the expression of certain chromosome, genes that stimulate cell growth might be amplified, eventually leading to uncontrolled cell cycle and malignant transformation.
 
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       The CRISPR/Cas9 system can be used for gene editing purposed including inserting genes, deleting genes, and creating breaks in the DNA.
 
       The CRISPR/Cas9 system can be used for gene editing purposed including inserting genes, deleting genes, and creating breaks in the DNA.
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<h3 class = "day"> Predicted CRISPR/Cas9 System </h3>
 
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<h3 class = "day"> Predicted & Modeled Transfection Results </h3>
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Based on previous CRISPR/Cas9 knock out procedures, ecDNA cell count is predicted to considerably reduce(10-20%) after transfection procedures. The broad estimations of the reductions of cell growths and cell growth rate lead to the hypothesis that the modification of ecDNA could result in exponential reductions of rates compared to control along a short time frame. After the  transfection procedure on ecDNA cells, experimental groups are expected to react to a different degree based on the individual guide RNA. This should result in distinctive, yet statistically significant experimental group cell count reduction over time.
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Latest revision as of 01:53, 2 November 2017

Modeling

CRISPR/Cas9 System

The CRISPR/Cas9 system can be used for gene editing purposed including inserting genes, deleting genes, and creating breaks in the DNA.

Predicted CRISPR/Cas9 System

In our first three test groups, we will only be using one guide RNA for each cell culture. The CRISPR/Cas9 will create a double strand break at the target sequence, leaving the ecDNA in two pieces. breaks in the DNA.

In our 4th test group, we will be using 3 guide RNAs for each cell culture. This will create double strand breaks at 3 target sequences, leaving the ecDNA in 6 pieces. We would like to test this because the more breaks we create in the ecDNA, the harder it is for the ecDNA to ligate back together.

Predicted & Modeled Transfection Results

Based on previous CRISPR/Cas9 knock out procedures, ecDNA cell count is predicted to considerably reduce(10-20%) after transfection procedures. The broad estimations of the reductions of cell growths and cell growth rate lead to the hypothesis that the modification of ecDNA could result in exponential reductions of rates compared to control along a short time frame. After the transfection procedure on ecDNA cells, experimental groups are expected to react to a different degree based on the individual guide RNA. This should result in distinctive, yet statistically significant experimental group cell count reduction over time.