Beyond DNA: Searching For Additional Flaws in Cancer’s Defenses
School: Los Alamos High
Area of Science: Medicine
Interim: Team Number: 71
School Name: Los Alamos High School
Area of Science: Medicine
Project Title: Beyond DNA: Searching For Additional Flaws in Cancer’s Defenses
Cancer has been a consistent cause of death in the world, and often when it strikes, it is near impossible to defeat. Cancer can be defined as a mutation in a cell’s DNA that causes the cell to multiply, without dying, at an exponential rate, which can lead to the formation of a tumor, and, in some cases, death. Many modern day treatments, such as chemotherapy, target Cancer by attacking the DNA of cancer cells, thereby preventing them from replicating further. This treatment, however, is not 100% effective, and often has several negative side effects, such as the destruction of digestive cell. This often causes the person receiving the therapy to vomit.
The key to defeating Cancer lies in the differences that distinguish cancer cells from normal healthy cells. By exploiting such differences, cancer cells can be attacked without harming other cells. This, however, has been a challenge since the main difference between cancerous and healthy cells lies in their DNA, where certain genes that normally cause the cell to undergo apoptosis (cell death) are turned off, and other genes that promote cell reproduction are stimulated so that the cells are constantly being replicated and never die. An alternative to targeting the DNA of cancer cells, however, would be to instead target the excretion of lactic acid from the cells.
This type of treatment would pertain exclusively to cancer cells since cancer cells shut down the mitochondria present in the cells that normally contribute greatly to apoptosis. In healthy cells, when glucose enters the cell, it undergoes a process known as glycolysis that converts glucose into pyruvate. From there, the pyruvate is usually converted into water, CO2, and energy that the cell can use through the CAC (Citric Acid Cycle) or Krebs Cycle and the ETC (Electron Transport Chain). In cancer cells though, the mitochondria are shut down. These cells therefore only undergo glycolysis, which, without the mitochondria, act as if the cell were producing energy anaerobically (without O2), as in intense exercise, and will undergo fermentation from glycolysis to produce energy for the cell, producing lactic acid in the process. The lactic acid is then secreted from the cell through a series of enzymes that excrete the lactic acid from the cell through facilitated diffusion. Facilitated diffusion is where certain membrane proteins help to move the lactic acid against the concentration gradient, so that it leaves the cell and enters the bloodstream. If the lactic acid is not excreted from the cell, the pH inside the cell (as well as other factors) will increase, causing the cell to die.
Therefore, the goal of this project is to design a computational program that could simulate the various enzyme and protein interactions used to excrete the lactic acid from the cell, and then to determine how affecting certain parts of that process would affect the excretion of lactic acid from the cell, and therefore determine which of those is most useful in hindering excretion of lactic acid from the cell, thereby destroying the cancer cells and the cancer itself.
The computational model shall be structured based on a differential system of equations. The rate at which the components of the glycolysis cycle are produced (the rate of enzymatic reactions) will be modeled by the equations:
v1=k1*S1 and v2=k2*S2 (which are based on the differential equation dS2/dt=v1-v2) where:
S2= Glucose 6-phosphate
k2= Enzyme 2
dS2=rate of change, in glycolysis, of Glucose 6-phosphate
v1=rate of conversion, in glycolysis, for Glucose
v=rate of conversion from Glucose to Fructose 6-phosphate
At each “tick” the computer will calculate how much of each product is produced based on these reactions and based on each step of the glycolysis cycle. The initial conditions will be set at:
Progress to Date:
So far, much information has been gathered both on the enzymatic pathways that help the cell excrete the lactic acid from the cell, as well as how the lactic acid is produced and how it affects the cell’s functions. Additional research has been gathered that can help with the modeling of the enzymatic pathways used to excrete the lactic acid from the cell, as well as the processes by which glucose is taken in by the cell and converted to lactic acid (glycolysis) so that the program can be built.
By affecting various constituents of the process that excretes lactic acid from cells, the program will reveal how these variations play a role in the excretion process and whether any of these variations will decrease the amount of lactic acid excreted from the cell.
Team members(s): Devon Conradson
Sponsoring Teacher: Lee Goodwin
1) Agus, David B., and Kristin Loberg. The End of Illness. N.p.: Thorndike, 2012. Print.
2) Alberts, Bruce. Molecular Biology of the Cell. New York: Garlan2d Science, 2008. Print. Fith.
3)Bellenir, Karen. Cancer Sourcebook. Detroit, MI: Omnigraphics, 2011. Print.
4) Biology Ap Edition. N.p.: Glencoe/McGraw-Hill Post Secondary, 2012. Print.
5) Holmes, Raquell M. Modeling Metabolic Pathways-Glycolysis: A Few Reactions. Rep. BioQUEST, Mar. 2005. Web. 9 Dec. 2013.
6) "Holy Cross Web Directory." College Server Home. N.p., n.d. Web. 10 Dec. 2013. http://college.holycross.edu/.Removal of Lactic Acid -- Oxidation and Gluconeogenesi
7) Lambeth, Melissa J., and Martin J. Kushmerick. "A Computational Model for Glycogenolysis in Skeletal Muscle." Annals of Biomedical Egineering 30 (2002): 808-27. JWS Online-Model Details. Web. 9 Dec. 2013. http://jjj.biochem.sun.ac.za/.
8) Natterson-Horowitz, Barbara, and Kathryn Bowers. Zoobiquity: What Animals Can Teach Us about Health and the Science of Healing. New York: A.A. Knopf, 2013. Print.
9) Pecorino, Lauren. Why Millions Survive Cancer: The Successes of Science. Oxford: Oxford UP, 2011. Print.
Sponsoring Teacher: Lee Goodwin
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