<div class="gmail_quote"><span style="font-family: arial,sans-serif; font-size: 13px; border-collapse: collapse;"><div>El día martes 30 de marzo a las 11am, el Dr. Gustavo Stolovitzky (<a href="http://domino.watson.ibm.com/comm/research_people.nsf/pages/gustavo.index.html" target="_blank">http://domino.watson.ibm.com/comm/research_people.nsf/pages/gustavo.index.html</a>) dará una charla en el aula Federman, Pabellón 1.</div>
<div><br></div><div>Quedan todos invitados.</div><div><br></div><div>Título: Systems Biology of small and large scale gene regulatory networks</div><br>Resumen:
Technologies such as gene expression arrays and ChIP-on-chip/ChIP-seq
have emerged as powerful tools to dissect the complex network of gene
regulatory interactions between transcription factors and their
targets. I will present a newly developed algorithm with improved
sensitivity in detecting binding events from ChIP-on-chip data applied
to human T cells, followed by extensive biochemical validation. This
analysis reveals that 3 oncogenic transcription factors, NOTCH1, MYC,
and HES1, bind to several thousand target gene promoters, up to an
order of magnitude increase over conventional analysis methods. The
increased sensitivity reveals a combinatorial regulatory program in
which MYC co-binds to virtually all NOTCH1-bound promoters. This large
scale complexity in the topology of transcriptional regulatory
networks, which highlights the fundamental importance of genome-scale
analysis to represent transcriptional programs, gives however a limited
level of detailed quantitative information on the system. Therefore
these approaches need to be complemented with more detailed modeling of
the biological system if we want to understand the details of the
dynamics that arise when we zoom in smaller scale behavior. To
highlight the richness of the dynamics at the smaller scales, we
discuss the concentration oscillations in the p53 signaling pathway
when a cell's DNA is damaged. In our model, the presence of double
stranded DNA breaks is transduced by ATM, a kinase that acts as the
input to a downstream oscillator consisting of a p53-Mdm2
autoregulatory feedback loop. Our simulations results show that p53 and
Mdm2 exhibit a coordinated oscillatory dynamics upon IR stimulation,
with a stochastic number of oscillations whose mean increases with IR
dosage, in good agreement with the observed response of p53 to
DNA-damage in single-cell experiments. The proposed model allows for
specific predictions. In yet another decrease in scale, we will discuss
how a single nucleotide polymorphism in the mdm2 gene (SNP309), which
enhances mdm2 transcription levels, can make p53 oscillations
disappear. Indeed, oscillations of p53 and Mdm2 are observed in the
cells wild type for mdm2 SNP309 but not in cells homozygous for mdm2
SNP309. In summary, we will go from the large scale organization of
the cell's gene regulatory network, down to smaller scales and higher
levels of detail, to explore the dynamics of a cellular pathway that,
threading at finer scales can be disrupted by a single nucleotide
polymorphism. </span>
</div>
<br clear="all"><br clear="all"><br>-- <br> Dr. Ariel Chernomoretz<br> Departamento de Fisica, FCEyN, Universidad de Buenos Aires,<br> (1428) Ciudad Universitaria, Ciudad de Buenos Aires, Argentina.<br>
TE +54 11 4576 3390 ext 817<br> Fax +54 11 4576 3357<br> email: <a href="mailto:ariel@df.uba.ar">ariel@df.uba.ar</a> Webpage: <a href="http://www.df.uba.ar/users/ariel">http://www.df.uba.ar/users/ariel</a><br>