From: Koonin, Eugene (NIH/NLM/NCBI)
Sent: Monday, August 22, 2005 8:21 PM
To: NLM/NCBI List ncbi-seminar
Cc: 'Cheol-Min Ghim'
Subject: Seminar September 1

Thursday, September 1, 11 AM

Bldg. 38A, B2 conference room


Cheol-Min Ghim 

Center for Theoretical Biological Physics University of California, 
San Diego

Lethality and synthetic lethality in the genome-wide metabolic network of
Escherichia coli
****************************************************************************
Recent genomic analyses on the cellular metabolic network show that reaction
flux across enzymes are diverse and exhibit power-law behavior in its
distribution. While intuition might suggest that the reactions with larger
fluxes are more likely to be lethal under the blockade of its catalysing
gene products or gene knockouts, we find, by in silico flux analysis, that
the lethality rarely has correlations with the flux level owing to the
widespread backup pathways innate in the genome-wide metabolism of
Escherichia coli. Lethal reactions, of which the deletion generates
cascading failure of following reactions up to the biomass reaction, are
identified in terms of the Boolean network scheme as well as the flux
balance analysis. The avalanche size of a reaction, defined as the number of
subsequently blocked reactions after its removal, turns out to be a useful
measure of lethality. As a means to elucidate phenotypic robustness to a
single deletion, we investigate synthetic lethality in reaction level, where
simultaneous deletion of a pair of nonlethal reactions leads to the failure
of the biomass reaction. Synthetic lethals identified via flux balance and
Boolean scheme are consistently shown to act in parallel pathways, working
in such a way that the backup machinery is compromised.

Eugene V. Koonin, PhD, Senior Investigator
National Center for Biotechnology Information
National Library of Medicine
National Institutes of Health
Bethesda, MD 20894
Telephone 301-435-5913
Fax 301-435-7794