Personal profile
Research interests
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.
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Collaborations and top research areas from the last five years
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Quantifying the intra- and inter-species community interactions in microbiomes by dynamic covariance mapping
Gencel, M., Cofino, G. M., Hui, C., Sahaf, Z., Gauthier, L., Matta, C., Gagné-Leroux, D., Tsang, D. K. L., Philpott, D. P., Ramathan, S., Menendez, A., Bershtein, S. & Serohijos, A. W. R., 1 Dec 2025, In: Nature Communications. 16, 1, 6314.Research output: Contribution to journal › Article › peer-review
Open Access3 Scopus citations -
The homeostasis of β-alanine is key for Arabidopsis reproductive growth and development
Wu, S., Zhang, Y., Luzarowska, U., Yang, L., Salem, M. A., Thirumalaikumar, V. P., Sade, N., Galperin, V. E., Fernie, A., Sampathkumar, A., Bershtein, S., Fusari, C. M. & Brotman, Y., 1 Apr 2025, In: Plant Journal. 122, 1, e70134.Research output: Contribution to journal › Article › peer-review
Open Access2 Scopus citations -
Correction to: Non-consecutive enzyme interactions within TCA cycle supramolecular assembly regulate carbon-nitrogen metabolism (Nature Communications, (2024), 15, 1, (5285), 10.1038/s41467-024-49646-7)
Jasinska, W., Dindo, M., Cordoba, S. M. C., Serohijos, A. W. R., Laurino, P., Brotman, Y. & Bershtein, S., 1 Dec 2024, In: Nature Communications. 15, 1, 6196.Research output: Contribution to journal › Comment/debate
Open Access -
Non-consecutive enzyme interactions within TCA cycle supramolecular assembly regulate carbon-nitrogen metabolism
Jasinska, W., Dindo, M., Cordoba, S. M. C., Serohijos, A. W. R., Laurino, P., Brotman, Y. & Bershtein, S., 1 Dec 2024, In: Nature Communications. 15, 1, 5285.Research output: Contribution to journal › Article › peer-review
Open Access13 Scopus citations -
The Fitness Effects of Codon Composition of the Horizontally Transferred Antibiotic Resistance Genes Intensify at Sub-lethal Antibiotic Levels
Shaferman, M., Gencel, M., Alon, N., Alasad, K., Rotblat, B., Serohijos, A. W. R., Alfonta, L. & Bershtein, S., 1 Jun 2023, In: Molecular Biology and Evolution. 40, 6, msad123.Research output: Contribution to journal › Article › peer-review
Open Access7 Scopus citations -
A High-Throughput Continuous Spectroscopic Assay to Measure the Activity of Natural Product Methyltransferases
Simon-Baram, H., Roth, S., Niedermayer, C., Huber, P., Speck, M., Diener, J., Richter, M. & Bershtein, S., 5 Sep 2022, In: ChemBioChem. 23, 17, e202200162.Research output: Contribution to journal › Article › peer-review
Open Access12 Scopus citations -
Evolution of homo-oligomerization of methionine S-adenosyltransferases is replete with structure–function constrains
Kleiner, D., Shapiro Tuchman, Z., Shmulevich, F., Shahar, A., Zarivach, R., Kosloff, M. & Bershtein, S., 1 Jul 2022, In: Protein Science. 31, 7, e4352.Research output: Contribution to journal › Article › peer-review
Open Access5 Scopus citations -
Metabolic response to point mutations reveals principles of modulation of in vivo enzyme activity and phenotype
Bhattacharyya, S., Bershtein, S., Adkar, B. V., Woodard, J. & Shakhnovich, E. I., 1 Jun 2021, In: Molecular Systems Biology. 17, 6, e10200.Research output: Contribution to journal › Article › peer-review
Open Access8 Scopus citations -
Predicting 3D protein structures in light of evolution
Bershtein, S., Kleiner, D. & Mishmar, D., 1 Sep 2021, In: Nature Ecology and Evolution. 5, 9, p. 1195-1198 4 p.Research output: Contribution to journal › Comment/debate
7 Scopus citations -
Samase of bacteriophage t3 inactivates escherichia coli’s methionine s-adenosyltransferase by forming heteropolymers
Simon-Baram, H., Kleiner, D., Shmulevich, F., Zarivach, R., Zalk, R., Tang, H., Ding, F. & Bershtein, S., 1 Aug 2021, In: mBio. 12, 4, e01242-21.Research output: Contribution to journal › Article › peer-review
Open Access9 Scopus citations
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NSF-BSF: Unraveling the molecular determinants of protein oligomerization
Bershtein, S. (PI) & Gaucher, E. (CoPI)
United States-Israel Binational Science Foundation (BSF)
1/01/20 → …
Project: Research
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Understanding the dynamics of protein evolution from a biophysical-organismal perspective
Bershtein, S. (CoPI), Kishony, R. (PI) & Shakhnovich, E. I. (CoPI)
Human Frontier Science Program
1/01/09 → …
Project: Research
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Bacterial adaptation by interface evolution of methionine S-adenosyltransferases (MATs)
Bershtein, S. (PI)
1/01/21 → 31/12/25
Project: Research
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The role of protein quality control in bacterial adaptive evolution driven by horizontal gene transfer
Bershtein, S. (PI)
1/01/15 → 31/12/18
Project: Research
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Understanding the dynamics of protein evolution from a biophysical-organismal perspective
Bershtein, S. (CoPI), Shakhnovich, E. I. (PI) & Kishony, R. (CoPI)
Human Frontier Science Program
1/01/09 → 31/12/11
Project: Research