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

2. 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. 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::Geminin is 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