There is a growing appreciation that horizontal gene transfer (HGT) is a major force in bacterial evolution. HGT produces extremely dynamic bacterial genomes in which substantial amounts of DNA from distantly related organisms flow into and from the chromosome, thus effectively shaping the ecological and pathogenic character of bacterial species. Whilst the genetic mechanisms responsible for the horizontal acquisition of foreign genes are well characterized, the molecular constraints to accommodation of the new genes within the cellular environment and networks of the recipient organisms remain largely unknown. Our lab strives to unearth the molecular mechanisms that control the functional integration of the horizontally transferred proteins into the host organism, and the adaptive evolution the follows HGT.

The research in our lab is undertaking two major directions:
1. Elucidating the molecular and systems-level mechanisms that control the accommodation of the horizontally transferred proteins, including the interaction with protein homeostasis machinery and the integration within transcriptional, metabolic and protein-protein interaction networks.
2. Understanding how these mechanisms modulate the fitness cost and adaptive potential of HGT.
We are particularly interested in the horizontal transfer of genes involved in folate transport and metabolism, and the HGT-driven adaptive evolution towards folate utilization and antifolate resistance. We generate and study collections of strains carrying the horizontally transferred genes using bioinformatics, microbial genetics, in vitro biophysical and biochemical molecular characterization, systems-level analysis, and high-throughput experimental evolution. We believe that the research in our lab will advance the understanding of the molecular mechanisms that drive microbial evolution and provide important insights into the genotype-phenotype relation.

Bershtein S, Serohijos, AWR, Bhattacharyya S, Manhart M, Choi J-M, Mu W, Zhou J, Shakhnovich EI. (2015) Protein homeostasis imposes a barrier on functional integration of horizontally transferred genes in bacteria. PloS Genet. 11(10):e1005612

Palmer AC., Toprak E, Baym M, Kim S, Veres A, Bershtein S, Kishony R. (2015) Delayed commitment to evolutionary fate in antibiotic resistance fitness landscapes. Nat Commun. 6: 7385-7392.

Bershtein S, Choi J-M, Bhattacharyya S, Budnik B, Shakhnovich IE. (2015) Systems-level response to point mutations in a core metabolic enzyme modulates genotype-phenotype relationship. Cell Rep. 11: 645-56.

Bershtein, S., Mu, W., Serohijos, A.W., Zhou, J., & Shakhnovich, I.E. (2013) Protein quality control acts on folding intermediates to shape the effects of mutations on organismal fitness. Mol Cell. 49: 133-44.

Weizmann Institute of Science, 2007