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Systems biology of responses of human cells (Maestro project)

Systems biology of responses of human cells (Maestro project). October 9, 2012. Brief Summary of Aims. Aim 1 Construct a new stochastic model of dynamics of transcription, translation and signal transduction, intertwined with growth regulation, unequal division and death of cells .

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Systems biology of responses of human cells (Maestro project)

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  1. Systems biology of responses of human cells(Maestro project) October 9, 2012

  2. Brief Summary of Aims Aim 1Construct a new stochastic model of dynamics of transcription, translation and signal transduction, intertwined with growth regulation, unequal division and death of cells. Aim 2 Derive a new stochastic model of evolution of early cancer, which includes cell selection and communication and validate it using existing biological and medical data Aim 3 Carry out analysis of regulatory sequences in the promoter and un-translated regions of genes involved in early carcinogenesis

  3. Aim 1 Construct a new stochastic model of dynamics of transcription, translation and signal transduction, intertwined with growth regulation, unequal division and death of cells. • Mathematical modeling work • Resurrect cell regulation and unequal division models (homeostasis and perturbations, sensitivity, etc.) • Collaboration with Zbigniew Darzynkiewicz and Dena Jackson on S-phase progression • (Kimmel, Smieja, Swierniak) • Data • FUCCI Marker Kinetics (courtesy of Franck Delauney, C5SYS project, U. Niece) • Yeast data on cell cycle (courtesy of Eric Siggia, Rockefeller U.) • Original experimentation (Biofarma)?

  4. Fucci Markers and Lineage Tracker Our FUCCI system expresses 2 cell cycle markers fused with fluorescent proteins as follows: mKO2::hCdt1 is a red fluorescent protein expressed only during the G1 phase. E2-Crimson::Gemininis a far-red fluorescent protein expressed during the S-G2-M phases. As a consequence, we usually consider that the G1 phase goes from the time of cell division to the peak of red (mKO2) fluorescence. When mKO2 fluorescence decreases, cells enter S phase. Then it is not possible to decipher between S/G2 and M phases.

  5. Aim 2 Derive a new stochastic model of evolution of early cancer, which includes cell selection and communication and validate it using existing biological and medical data • Mathematical modeling work • Spatial communication models (Fujarewicz?) • Recent work on leukemias (Kimmel, collaboration with Seth Corey and Cristian Tomasetti) • Data • Original experimentation (do we have laboratory systems at our disposal)? • Cell communication (?) (Prof. Rzeszowska)

  6. Aim 3 Carry out analysis of regulatory sequences in the promoter and un-translated regions of genes involved in early carcinogenesis • Bioinformatics and physical modeling of transcription regulation • Methodological work on models (Iwanaszko, Pacholczyk) • Analysis of expression of NF-kB and p53 with other associated pathways • Data • Original experimentation: ChipSeq analysis (Widlak, Szoltysek, Janus, Skonieczna) • Collaboration with Neil Perkins (Newcastle U.)

  7. Agenda • Discussion of feasibility of experimental work (Widlak, Rzeszowska) • Pizza • Short presentations • General discussion

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