Systems level studies of complex bacterial behavior

Our modern molecular understanding of life is the product of decades of focused research on a handful of domesticated species that by circumstance share the heavy burden of representing the entire diversity of life.  Fortunately, the core processes are highly conserved across phylogeny, providing us with a rather coherent, yet incomplete picture.  A serious challenge to this rule has confronted us for a few years now, when after more than a hundred complete bacterial genomes from a diversity of clades, the fraction of entirely novel ORFs (with no matches in the database) remains a surprisingly constant fraction of each genome.  Does this tip of the iceberg of novel proteins reflect a universe of unknown pathways?  From an ecological perspective, there seems no limit to the diversity of extreme environments in which bacteria thrive, accompanied by extreme metabolisms, and rather sophisticated behaviors.  As rich as our knowledge of E. coli biology has become, it nevertheless represents only a miniscule fraction of microbial life, and sequence homology can only take us so far.  We urgently need new approaches to systematically and rapidly elucidate the genetic basis of phenotypes in the large and growing population of bacteria of basic biological, environmental, and clinical importance.  To this end, we have developed a whole-genome quantitative fitness analysis method using microarray-based genetic footprinting, and are applying it to complex bacterial behaviors and phenotypes.  In addition to gaining insights into rapid adaptation to novel environments, we are exploring the genetic basis of surface behaviors such as swarming and biofilm formation.

Related publications:

Global protein occupancy landscape of a bacterial genome
Molecular Cell. 2009 Jul 31;35(2):247-53
Vora T., Hottes, AK., Tavazoie S.

Global discovery of adaptive mutations
Nature Methods. 2009 Aug; 6(8):581-3
Goodarzi H., Hottes, AK., Tavazoie S.

Genetic architecture of intrinsic antibiotic susceptibility.
PLoS ONE. 2009 May 20;4(5):e5629.
Girgis HS, Hottes AK, Tavazoie S.

Genetic dissection of an exogenously induced biofilm in laboratory and clinical isolates of E. coli.
PLoS Pathog. 2009 May;5(5):e1000432. Epub 2009 May 15.
Amini S, Goodarzi H, Tavazoie S.

Predictive behavior within microbial genetic networks
Science (2008) 320:1313-1317, Epub 2008 May 8
Tagkopoulos, I., Liu, Y. and Tavazoie, S.

A comprehensive genetic characterization of bacterial motility
PLoS Genetics (2007) 3 (9): e154
Girgis, H., Liu, Y., Ryu, W. and Tavazoie S.

Ab initio genotype-phenotype association reveals the intrinsic modularity of genetic networks.
Molecular Systems Biology 2006; 2:2006.0005. Epub 2006 Jan 31.
Slonim, N., Elemento, O. and Tavazoie, S.

A cross-genomic approach for systematic mapping of phenotypic traits to genes.
Genome Research 2004 Jan; 14(1):109-15.
Jim K., Parmar K., Singh M. and Tavazoie S.

Selection analyses of insertional mutants using subgenic-resolution arrays.
Nature Biotechnology 2001 19: 1060-1065.
Badarinarayana V., Estep P.W. 3rd, Shendure J., Edwards J., Tavazoie S., Lam F. and Church G.M.

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