Click to edit Margo Corsetti Mentor: Dr. Natasa Miskov-Zivanov DiSCoBio Acadamy
Click to edit • Chemotherapy & radiation: o Nonspecific o Continuous delivery • Improvements: o Target disease sites only o Deliver treatment in an appropriate time frame • Possible solution o Bacteria with attached anti-cancer agents
Click to edit • Cancer cells form tumor Cells without plasmid • Inject bacteria Cells with Cells with plasmid o Chemotaxis plasmid • Bacteria deliver plasmid • Releases a signal (luciferase)
Click to edit Stock Equation Cells with plasmid Losing Population loss Population gain plasmid Cells without plasmid growth rate Substrate depletion Depletion constants Luciferase expression Luciferase decay
Click to edit Netlogo Matlab
Click to edit substrate Cells with plasmid Cells without plasmid Luciferase
Click to edit Cells without plasmid Cells with plasmid Time- Stable targeted Time (hrs) Time (hrs) Proportional to Continuous Luciferase Substrate cells with consummation of plasmid substrate Time (hrs) Time (hrs)
Click to edit 1) Choose 1 parameter to vary Depletion rate constant of cells without plasmid Varying A- Decreasing A- by
Click to edit Cells without plasmid Cells with plasmid 2) Plot Functions Shifts peak Shifts peak left left Decreases Decreasing A- by Decreases peak peak 0% 10% 20% Time (hrs) Time (hrs) 30% Substrate Shifts peak 40% Luciferase left Decreases Decreases time to peak reach 0 Time (hrs) Time (hrs)
Click to edit 2) Record Results Increases depletion of • substrate Decreases maximal amount Decreases time for of • Cells with plasmid • Cells with plasmid • Cells without plasmid • Cells without plasmid • Luciferase • Luciferase to reach maximal amount
Click to edit • variance of certain parameters alters 3 main elements: o 1. the maximal growth of cells with and without the plasmid and the maximal luciferase expression o 2. The speed with which cells with and without the plasmid and luciferase reach their maximal values o 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.
Click to edit • Listeria at with attached radionuclides, 188 Rhenium • Targets pancreatic cancer met and tumor cells Cells without • Similarities with S.Typhurmirium radionuclides Cells with Cells with radionuclides Cells without radionuclides Cells with plasmid plasmid Cells with plasmid
Click to edit Stock Equation Listeria at with 188 Rhenium Losing Population gain Population loss Rhenium Listeria at without 188 Rhenium Attached 188 Rhenium Free 188 Rhenium Population loss
Click to edit Netlogo Matlab Agent-Based
Click to edit Listeria at enters cells and infects When cells them (yellow) die, they release Listeria at Radiolabeled Listeria at travels toward tumor
Click to edit Time- targeted Continuous consummation of substrate Stable
Click to edit Decline due to half-life As attached Rhenium decreases free Rhenium increases
Click to edit • Further investigate the behavior of Listeria at , specifically with attached radionuclides, for more accurate and detailed modeling in Matlab and Netlogo
Click to edit 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”
Click to edit • Dr. Natasa Miskov-Zivanov, PhD • Dr. Michael Lotze and the UPCI Academy • Team DiSCoBio and my peers • Team iGEM
Click to edit Questions?
Recommend
More recommend
