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BIOGRAPHY:
Dr. Gelfand received his Ph.D. in mathematics in 1993 from the Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, in Pushchino, and his D.Sc. in biology in 1998 from the Research Institute for the Genetics and Selection of Industrial Microorganisms in Moscow, where he currently holds the position of Leading Scientist. His HHMI-funded project is entitled "Comparative Genomics, Metabolic Reconstruction, and Analysis of Regulation in Bacterial Genomes."
RESEARCH ABSTRACT SUMMARY:
Comparative Genomics, Metabolic Reconstruction, and Analysis of
Regulation in Bacterial Genomes
Comparative genomics techniques were applied to the analysis of
several metabolic pathways and functional systems in bacteria (e.g.,
vitamins: cobalamin, thiamine; amino acids: lysine, methionine,
histidine, threonine, branched-chain, aromatic; sugars and
polysaccharides; stress response: heat shock, general stress, heavy
metal resistance). This work resulted in metabolic reconstructions of
these pathways, identification of numerous new enzymes and
transporters, and prediction of new regulatory systems.
In particular, we continued to study riboswitches, a new class of
regulatory RNA elements. We identified numerous new instances of
riboswitches, described in detail their mode of action (repression or
activation, attenuation of transcription or translation), and studied
their evolution and interaction with other regulatory systems. In
gram-positive bacteria, the riboswitch appears to be the primary
regulator of the methionine pathway, whereas in lactococci this role is
assumed by T-boxes and in streptococci by the MtaR transcriptional
repressor. A new mechanism of riboswitch regulation in actinobacteria
involves direct sequestering of the ribosome-binding site.
Lysine-dependent riboswitches may activate genes for the lysine
catabolism pathway in several genomes.
Analysis of zinc regulons enabled us to identify a family of
proteins likely involved in pathogenesis caused by streptococci.
Repression by zinc was predicted for genes encoding paralogues of
ribosomal proteins containing the zinc-ribbon motif. We identified new
regulatory signals for the zinc repressor AdcR, the methionine
repressor MtaR, two regulators of aromatic amino acid biosynthetic
operons, and numerous transcription factors from the LacI family. New
enzymes were identified in the pathways of cobalamin, thiamine (ThiN),
lysine (branch of acetylated intermediates in Bacillus
subtilis), and methionine (recycling and reverse synthesis of
cysteine from methionine branches).
Several of our predictions were
confirmed through experiments conducted by collaborators and in
independent studies.
Photo: Kent Kallberg, Kallberg Studios
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