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A Dynamic Biochemical Network Analysis and Gene
Regulation Network Analysis for in vivo biological systems
By
Dr
Masa Tsuchiya, Ph.D.
Senior Scientist
Bioinformatics Institute Singapore (BII)
Venue:
SBS Classroom 2
Date: 26 April 2005, Tuesday
Time: 3.00 - 4.00 pm
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Abstract:
My
talk will address two parts: a dynamic biochemical network analysis
and gene regulation network analysis for in vivo biological systems.
It has been well known that there are fundamental experimental and
theoretical difficulties in determining biochemical kinetics including
kinetic parameters such as rate coefficients. Recently, Dr. Kumar
Selvarajoo and I have succeeded in developing a dynamical network
analysis for in vivo metabolic experiments. This dynamical approach
is to extract biochemical network connectivity based on perturbation
-response experiments. This technique can be applied to uncover
the metabolic pathway, genetic network and protein signaling pathway,
e.g. to capture potential bio-markers for drug target discovery.
As a proof of principle, we have applied the analysis to perturbation-response
experiment on in vivo glycolysis pathway in Saccharomyces cerevisiae
to predict the actual dynamical network behaviour and network connectivity
in metabolic dynamics.
In
the second part, I will address a novel cis-regulatory network analysis
for P53 auto regulatory feedback loop system. The tumor suppressor
p53 is one of the most important genes in maintaining genomic stability
and in ensuring the proper elimination of damaged or tumorigenic
cells. Some of the key cellular processes controlled by p53 activity
include apoptosis, cell cycle arrest, senescence and accelerated
DNA repair etc. Due to its critical role in guarding against cancer
development, p53 has been the subject of intense research for the
past decades. I will discuss sequential logic modeling to elucidate
transcriptional control of p53 gene expression and an auto-regulatory
feedback loop of p53 by MDM2 protein.
Biodata
of Speaker:
Dr.
Masa Tsuchiya (theoretical physicist) joined BII as a senior scientist
in October 2004. Prior to BII, he has been a senior staff scientist
at the Stanford Genome Technology Center and a research assistant
professor, Stanford Medical School. Through the years, he has worked
on particle physics, quantum chaos, chemical spectroscopy and kinetics,
and genomics. In 2002, he has developed novel systematic approaches
to understand complex biochemical reaction networks in collaboration
with a leading scientist of nonlinear chemistry, Prof. John Ross
(Chemistry, Stanford University). He will be an editor of new Journal,
“Journal of Systems and Synthetic Biology”, BioMed Central,
UK, 2005. His current interest is to understand the dynamics of
genetic diseases through the development, modeling and integration
of gene regulatory networks and biochemical networks.
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