Evolutionary plasticity of cell-cycle regulation

112
Evolutionary plasticity of cell- cycle regulation Lars Juhl Jensen

Transcript of Evolutionary plasticity of cell-cycle regulation

Evolutionary plasticity of cell-cycle regulation

Lars Juhl Jensen

sequence analysis

Jensen & Knudsen, Bioinformatics, 2000

Jensen, Gupta et al., Journal of Molecular Biology, 2002

data integration

Szklarczyk, Franceschini et al., Nucleic Acids Research, 2011

Jensen & Bork, Science, 2008

Campillos, Kuhn et al., Science, 2008

signaling networks

Miller, Jensen et al., Science Signaling, 2008

Linding, Jensen, Ostheimer et al., Cell, 2007

text mining

Pafilis, O’Donoghue, Jensen et al., Nature Biotechnology, 2009

the cell cycle

complex process

one cell

two cells

regulation

gene expression

protein complexes

phosphorylation

targeted degradation

gene expression

cell cultures

S. cerevisiae

synchronization

microarrays

time courses

Gauthier et al., Nucleic Acids Research, 2007

cycling genes

renormalization

reanalysis

new scoring scheme

benchmarking

Gauthier et al., Nucleic Acids Research, 2007

protein complexes

interaction data

temporal network

de Lichtenberg, Jensen et al., Science, 2005

de Lichtenberg, Jensen et al., Science, 2005

hypothesis

just-in-time assembly

de Lichtenberg, Jensen et al., Cell Cycle, 2007

how can we test it?

evolutionary flexibility

reanalysis

microarray time courses

S. pombe

H. sapiens

A. thaliana

cycling genes

orthologous genes

Jensen, Jensen, de Lichtenberg et al., Nature, 2006

protein complexes

Jensen, Jensen, de Lichtenberg et al., Nature, 2006

phosphorylation

CDK substrate

low-throughput data

high-throughput data

NetPhosK

correlation

Jensen, Jensen, de Lichtenberg et al., Nature, 2006

Jensen, Jensen, de Lichtenberg et al., Nature, 2006

correlated changes

Jensen, Jensen, de Lichtenberg et al., Nature, 2006

Jensen, Jensen, de Lichtenberg et al., Nature, 2006

co-evolution

transcriptional regulation

posttranslational regulation

phosphoproteomics

SILAC study of HeLa cells

multi-block strategy

Olsen, Vermeulen et al., Science Signaling, 2010

cycling proteins

Olsen, Vermeulen et al., Science Signaling, 2010

regulation of kinases

Olsen, Vermeulen et al., Science Signaling, 2010

regulation by kinases

Olsen, Vermeulen et al., Science Signaling, 2010

evolution of cycles

other periodic processes

microarray time courses

ultradian cycle

S. cerevisiae

Trachana, Jensen & Bork, EMBO Reports, 2010

diurnal cycle

A. thaliana

Trachana, Jensen & Bork, EMBO Reports, 2010

mammals

Trachana, Jensen & Bork, EMBO Reports, 2010

paralogous genes

same cellular functions

different periodic processes

three independent lineages

summary

reanalysis

integration

high-throughput data

biological discoveries

Acknowledgments

Just-in-time assemblyUlrik de Lichtenberg

Thomas Skøt Jensen

Søren Brunak

Peer Bork

Comparison with othercycling processesKalliopi Trachana

Peer Bork

ProteomicsJesper V. Olsen

Michiel Vermeulen

Anna Santamaria

Chanchal Kumar

Martin Lee Miller

Florian Gnad

Jürgen Cox

Thomas Skøt Jensen

Erich A. Nigg

Søren Brunak

Matthias Mann

larsjuhljensen