Click to edit Margo Corsetti Mentor: Dr. Natasa Miskov-Zivanov - - PowerPoint PPT Presentation

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Margo Corsetti Mentor: Dr. Natasa Miskov-Zivanov DiSCoBio Acadamy

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• Chemotherapy & radiation:
• Nonspecific
• Continuous delivery
• Improvements:
• Target disease sites only
• Deliver treatment in an appropriate time frame
• Possible solution
• Bacteria with attached anti-cancer agents

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• Cancer cells form tumor
• Inject bacteria
• Chemotaxis
• Bacteria deliver plasmid
• Releases a signal (luciferase)

Cells with plasmid Cells with plasmid Cells without plasmid

Click to edit Stock Equation Cells with plasmid Cells without plasmid Substrate depletion Luciferase expression Population gain Population loss Losing plasmid Depletion constants Luciferase decay growth rate

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Matlab Netlogo

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Cells with plasmid substrate Cells without plasmid Luciferase

Click to edit Luciferase Cells with plasmid Time (hrs) Substrate Time (hrs) Time (hrs) Cells without plasmid Time (hrs) Time- targeted Stable Proportional to cells with plasmid Continuous consummation of substrate

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1) Choose 1 parameter to vary

Varying A- Depletion rate constant of cells without plasmid Decreasing A- by

Click to edit Cells without plasmid Time (hrs) Luciferase Substrate Time (hrs) Time (hrs) Cells with plasmid Time (hrs) Decreasing A- by 0% 10% 20% 30% 40%

2) Plot Functions

Decreases peak Shifts peak left Decreases peak Shifts peak left Decreases peak Shifts peak left Decreases time to reach 0

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2) Record Results

Decreases maximal amount

• f
• Cells with plasmid
• Cells without plasmid
• Luciferase

Decreases time for

• Cells with plasmid
• Cells without plasmid
• Luciferase

to reach maximal amount Increases depletion of

• substrate

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• variance of certain parameters alters 3 main

elements:

• 1. the maximal growth of cells with and without the plasmid and the

maximal luciferase expression

• 2. The speed with which cells with and without the plasmid and luciferase

reach their maximal values

• 3. The speed with which tumor substrate is depleted
• more concrete understanding of the roles each

parameter plays-we know which parameters to manipulate to gain the desired effect.

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• Listeriaat with attached radionuclides, 188Rhenium
• Targets pancreatic cancer met and tumor cells
• Similarities with S.Typhurmirium

Cells with plasmid Cells with plasmid Cells without plasmid Cells with radionuclides Cells without radionuclides Cells with radionuclides

Click to edit Stock Equation Listeriaat with 188Rhenium Listeriaat without 188Rhenium Attached 188Rhenium Free 188Rhenium Losing Rhenium Population gain Population loss Population loss

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Matlab Netlogo Agent-Based

Click to edit Radiolabeled Listeriaat travels toward tumor Listeriaat enters cells and infects them (yellow) When cells die, they release Listeriaat

Click to edit Time- targeted Stable Continuous consummation of substrate

Click to edit Decline due to half-life As attached Rhenium decreases free Rhenium increases

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• Further investigate the behavior of Listeriaat ,

specifically with attached radionuclides, for more accurate and detailed modeling in Matlab and Netlogo

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• 1. ACS Synthetic Biology 2012 “In Vivo Gene

Expression Dynamics of Tumor-Targeted Bacteria”

• 2. PNAS 2013 “Nontoxic radioactive Listeria at is a

highly effective therapy against metastatic pancreatic cancer”

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• Dr. Natasa Miskov-Zivanov, PhD
• Dr. Michael Lotze and the UPCI Academy
• Team DiSCoBio and my peers
• Team iGEM

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Questions?