04 Kimmel, Marek

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  • 04 Kimmel, Marek

    1. 1. Marek Kimmel, PhD <ul><li>1980 PhD Silesian Tech, Gliwice. Poland </li></ul><ul><li>1982-1990 Memorial Sloan-Kettering Cancer Center (NYC) </li></ul><ul><li>1990-present Dept. Statistics, Rice Univ. </li></ul><ul><li>Interests: </li></ul><ul><ul><li>Stochastic processes (branching processes) </li></ul></ul><ul><ul><li>Population and statistical genetics (see dr. Plon’s talk) </li></ul></ul><ul><ul><li>Stochastic models in cell biology </li></ul></ul><ul><li>Taught classes; advised students, postdocs and junior faculty </li></ul>
    2. 2. Marek Kimmel, PhD <ul><li>Monographs </li></ul><ul><ul><li>Kimmel M and Axelrod DE (2002) Branching Processes in Biology . Springer, NY </li></ul></ul><ul><ul><li>Polanski A and Kimmel M (2007) Bioinformatics , Springer, Berlin. </li></ul></ul><ul><li>  Publications (150) </li></ul><ul><ul><li>PubMed (kimmel m) </li></ul></ul><ul><ul><li>MathSci Net (kimmel, m*) </li></ul></ul><ul><li>Research Support Past and Present: NIH, NSF, NATO, KBN </li></ul><ul><li>Editorial Boards: JTB, MBS, JNCI, BD </li></ul><ul><li>Collaborations: BCM, MDA, Silesian Tech, U Liverpool, MBI </li></ul>
    3. 3. Stochastic effects in cell proliferation
    4. 5. Colony of E. coli cells
    5. 6. Sectoring Phenotype 4 Red Sectors in Streak-out Section <ul><li>Set our original cut-off at >4 sectors per 1/8 plate streak </li></ul><ul><li>~150-180 single/distinguishable colonies in 1/8 plate streak </li></ul>
    6. 7. Cumulative distributions of colony sizes via branching processes
    7. 8. Telomere shortening
    8. 9. Incomplete DNA replication problem (1) <ul><li>Incomplete replication problem: DNA polymerase moves in one direction and 3’-ends are not copied. </li></ul><ul><li>In bacteria no problem, since chromosomes are circular. </li></ul>
    9. 10. Telomere lengths in cloned sheep Shiels et al (1999) Nature  Cloned  Control
    10. 11. Consequences of telomere shortening <ul><li>Most cells that lost their telomeres stop proliferating (Hayflick limit). </li></ul><ul><li>Some cells escape the Hayflick limit but as a consequence their chromosomes may mis-segregate at mitosis, leading to rearrangements. </li></ul><ul><li>Chromosomal rearrangements, including those caused by telomere shortening are considered one of the causes of cancer. </li></ul>
    11. 12. Why is stochastic signal transduction/regulation important? <ul><li>Stochasticity at the single cell level produces population variability </li></ul><ul><li>Variability makes the cell population respond to the stimuli in a more robust way </li></ul><ul><li>Stochasticity might be favored by evolution </li></ul>
    12. 13. Intrinsic sources of stochasticity <ul><li>In bacteria, single-cell level stochasticity is quite well-recognized, since the number of mRNA or even protein of given type, per cell, might be small (1 gene, several mRNA, protein ~10) </li></ul><ul><li>Eukaryotic cells are much larger (1-2 genes, mRNA ~100, protein ~100,000), so the source of stochasticity might be the regulation of gene activity. </li></ul>
    13. 14. Nuclear Receptor Regulation at the Promoter Other CoA’s RNA Polymerase General Transcription Factors PGCs TRAP/ DRIP ASC1/2 P/CAF TRIP230 WPBs ARA70 CARM1 UbcH7 CBP Itch SSA Rb Transcription E6-AP BRG1 SRA p160’s Variable Output ER ER HRE Reporter Gene TATA
    14. 16. White et al. experiments

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