Associate Professor Jonathan Dworkin Phone: 212-342-3731 Lab Phone: 212-305-0316 Fax: 212-305-1468 Email: jed2113@columbia.edu

Associate Professor Jonathan Dworkin
Phone: 212-342-3731
Lab Phone: 212-305-0316
Fax: 212-305-1468
Email: jed2113@columbia.edu

Jonathan Dworkin, Ph.D.

Professor of Microbiology & Immunology
Ph.D., Rockefeller University

Research
My laboratory is interested in the mechanisms used by quiescent cells to survive stressful conditions, such as nutrient limitation with particular attention on how these strategies affect antibiotic sensitivity including the emergence of tolerance (“persisters”). We focus on the down-regulation of protein synthesis, with most recent work examining the nucleotide ppGpp and the protein Hibernation Promoting Factor which induces ribosome dimerization. Our work employs a range of techniques, ranging from genetics and physiology to in vitro biochemistry and single molecule biophysical studies.

 

Selected Publications

  1. Nygaard, R., Graham, C.L.B., Dufrisne, M., Colburn, J.D., Pepe, J., Hydorn, M.,  Kloss, B., Clarke, O.B., Columbus, L.*, Dworkin, J.*, Stansfeld, P.J.*, Roper, D.* and Mancia, F.* (2023) Structural basis of peptidoglycan synthesis by E. coli RodA-PBP2 complex. Nature Commun. 14: 5151. https://doi.org/10.1038/s41467-023-40483-8 (*Co-corresponding authors)

  2. Feaga, H.A., Hong, H.R., Prince, C.R., Rankin, A., Buskirk, A.R. and Dworkin, J. (2023) Elongation factor P is important for sporulation initiation. J. Bacteriol. 205: e0037022. https://doi.org/10.1128/jb.00370-22

  3. Huemer, M., Mairpady Shambat, S., Hertegonne, S., Bergada-Pijuan, J., Chang, C. C., Pereira, S., Gómez-Mejia, A., Van Gestel, L., Bär, J., Vulin, C., Pfammatter, S., Stinear, T.P., Monk, I.R., Dworkin, J. and Zinkernagel, A.S. (2023). Serine-threonine phosphoregulation by PknB and Stp contributes to quiescence and antibiotic tolerance in Staphylococcus aureus. Science Signaling 16: eabj8194. https://doi.org/10.1126/scisignal.abj8194

  4. Dworkin, J. and Harwood, C.S. (2022) Metabolic reprogramming and longevity in quiescence. Annual Review of Microbiology 76: 91–111. https://doi.org/10.1146/annurev-micro-041320-111014

  5. Diez, S., Hydorn, M., Whalen, A. and Dworkin, J. (2022) Crosstalk between guanosine nucleotides regulates cellular heterogeneity in protein synthesis during nutrient limitation. PLoS Genetics 18: e1009957. https://doi.org/10.1371/journal.pgen.1009957

  6. Feaga, H.A. and Dworkin, J. (2021) Transcription regulates ribosome hibernation. Mol. Microbiol. 116: 663–673. https://doi.org/10.1111/mmi.14762

  7. Feaga, H.A., Kopylov, M., Kim, J.K., Jovanovic, M. and Dworkin, J. (2020) Ribosome dimerization protects the small subunit. J. Bacteriol. 202: e00009-20. https://doi.org/10.1128/JB.00009-20

  8. Diez, S., Ryu, J., Gonzalez Jr., R.L. and Dworkin, J. (2020) The alarmones (p)ppGpp directly regulate translation initiation during entry into quiescence. Proc. Natl. Acad. Sci. U.S.A. 117: 15565-15572.

  9. Atwal, S., Giengkam, S., Jaiyen, Y., Feaga, H.A., Dworkin, J. and Salje, J. (2020) Clickable methionine as a universal probe for labelling intracellular bacteria. Journal of Microbiological Methods 169: 105812.

  10. Libby, E.A, Reuveni, S. and Dworkin, J. (2019) Multisite phosphorylation drives phenotypic variation in (p)ppGpp synthetase-dependent antibiotic tolerance. Nature Communications 10: 5133.

  11. Feaga, H. and Dworkin, J. (2019) A wolf in sheep’s clothing: chromosomal pathogenicity islands co-opt phage capsids to facilitate horizontal spread. Molecular Cell 70: 1-2.

  12. Dworkin, J. (2018) Detection of fungal and bacterial carbohydrates: Do the similar structures of chitin and peptidoglycan play a role in immune dysfunction? PLoS Pathog. 14: e1007271.

  13. Rajagopalan, K. and Dworkin, J. (2018) Identification and biochemical characterization of a novel PP2C-like Ser/Thr phosphatase in E. coli. J. Bacteriol. 200: e00225-18.

  14. Libby, E.A. and Dworkin, J. (2017) Habits of highly effective biofilms: Ion signaling. Molecular Cell 66: 1.

  15. Sarkar, S., Libby, E.A., Pidgeon, S.E., Dworkin, J. and Pires, M.M. (2016) In vivo probe of Lipid II-interacting proteins. Angewandte Chemie doi: 10.1002/anie.201603441.

  16. Sturm, A. and Dworkin, J. (2015) Phenotypic diversity as a mechanism to exit dormancy. Current Biology 25: 1-6. (Cited in Dispatch, Current Biology 25: 45-47.)

  17. Libby, E. A., L.A. Goss and Dworkin, J. (2015) The eukaryotic-like Ser/Thr kinase PrkC regulates the essential WalRK two-component system in Bacillus subtilis. PLoS Genetics 11: e1005275.

  18. Pereira, S.P.P., Gonzalez, R. and Dworkin, J. (2015) Protein synthesis during cellular quiescence is inhibited by phosphorylation of a translational elongation factor. Proc. Natl. Acad. Sci. U.S.A. 112: e3274-3281.

  19. Dworkin, J. (2015) Ser/Thr phosphorylation as a regulatory mechanism in bacteria. Curr. Opin. Microbiol. 24C: 47-52.

  20. Dworkin, J. (2014) The medium is the message: interspecies and interkingdom signaling by peptidoglycan and related bacterial glycans. Annu. Rev. Microbiol. 68: 137-154.

  21. Dworkin, J. (2014) Protein targeting during sporulation. In The Bacterial Spore: From Molecules to Systems, Driks, A. and Eichenberger, P., Eds. ASM Press.

  22. Squeglia, F., Marchetti, R., Ruggiero, A., Lanzetta, R., Marasco, D., Dworkin, J., Pethoukov, M., Molinaro, A., Berisio, R. and Silipo, A. (2012) Chemical basis of peptidoglycan discrimination by PrkC, a key kinase Involved in bacterial resuscitation from dormancy. J. Amer. Chem. Soc.133: 20676-20679.

  23. Higgins D, Dworkin J. (2012) Recent progress in Bacillus subtilis sporulation. FEMS Microbiol Rev. 36: 131-148.

  24. Laaberki, M-H., Pfeffer, J., Clarke, A. and Dworkin J. (2011) O-acetylation of peptidoglycan is required for proper cell separation and S-layer anchoring in Bacillus anthracis. J. Biol Chem286: 5278-5288. [Download PDF]

  25. Pereira, S., Goss, L., and Dworkin, J. (2011) Eukaryote-like Ser/Thr kinases and phosphatases in bacteria. Microbiology and Molecular Biology Reviews 75: 1-21. [Download PDF]

  26. Dworkin, J. and Shah, I. (2010) Exit from dormancy in microbial organisms. Nature Reviews Microbiology 8: 890-896. [Download PDF]

  27. Dworkin, J. (2010) Form equals function? Bacterial shape and its consequences for pathogenesis. Mol. Microbiol. 78: 792-795. [Download PDF]

  28. Fay, A., Meyer, P. and Dworkin, J. (2010) Interactions between late-acting proteins required for peptidoglycan synthesis in sporulation. J. Mol. Biol. 399: 547-561. [Download PDF]

  29. Meyer, P., Gutierez, J., Pogliano, K. and Dworkin, J. (2010) Cell wall synthesis is necessary for membrane dynamics during sporulation of Bacillus subtilis. Mol. Microbiol. 76: 956-970. [Download PDF]

  30. Shah, I.M. and Dworkin, J. (2010) Induction and regulation of a secreted peptidoglycan hydrolase by a membrane Ser/Thr kinase that detects muropeptides. Mol. Microbiol. 75: 1232-1243. [Download PDF]

  31. Fay, A. and Dworkin, J. (2009) B. subtilis homologs of the putative Lipid II flippase E. coli MurJ (MviN) are not essential. J. Bacteriol. 191: 6020-6028. (Cited by Faculty of 1000) [Download PDF]

  32. Eldar, A., Chary, V., Xenopoulos, P., Fontes, M.E., Loson, O.C., Dworkin, J., Piggot, P. and Elowitz, M. (2009) Partial penetrance facilitates developmental evolution in bacteria. Nature460: 510-515. [Download PDF]

  33. Dworkin, J. (2009) Cellular polarity in prokaryotic organisms. Cold Spring Harb. Perspect. Biol.1: a003368. [Download PDF]

  34. Shah, I., and Dworkin J. (2009) Dispatch: Bacteria talk to (some) of their neighbors. Current Biology 19: R689-691. [Download PDF]

  35. Shah, I.M., Laaberki, M-H, Popham, D.L. Dworkin, J. (2008) A eukaryotic-like Ser/Thr kinase signals bacteria to exit dormancy in response to peptidoglycan fragments. Cell 135: 486-497. [Download PDF]

  36. Laaberki, M-H. and Dworkin, J. (2008) The role of spore coat proteins in the resistance of B. subtilis spores to C. elegans predation. J. Bacteriol. 190: 6197-6204. [Download PDF]

  37. Laaberki, M-H. and Dworkin, J. (2008) Death and survival of spore-forming bacteria in the Caenorhabditis elegans intestine. Symbiosis 46: 195-200. [Download PDF]

  38. Real, G., Fay, A., Eldar, A., Pinto, S.M., Henriques, A.O. and Dworkin, J. (2008) Determinants for the subcellular localization and function of a non-essential SEDS protein. J. Bacteriol. 190: 363-376.

  39. Suel, G., Kulkarni, R.P., Dworkin, J., Garcia-Ojalvo, J. and Elowitz, M. (2007) Tunability and noise dependence in differentiation dynamics. Science 315: 316-9. [Download PDF]

  40. Meyer, P. and Dworkin, J. (2007) Applications of fluorescence microscopy to single bacterial cells. Res. Microbio. 158: 187-194. [Download PDF]

  41. Dworkin, J. and Losick, R. (2005) Developmental committment in a bacterium. Cell 121: 401-409. [Download PDF]

  42. Dworkin J. (2003) Transient genetic asymmetry and cell fate in a bacterium. Trends in Genetics 19: 107-112. [Download PDF]

  43. Dworkin J. and Losick R. (2002) Does RNA polymerase help drive chromosome segregation in bacteria? Proc. Natl. Acad. Sci. U.S.A. 99: 14089-14094. [Download PDF]

  44. Dworkin J. and Losick R. (2001) Differential gene expression governed by chromosomal spatial asymmetry. Cell 107: 339-346. [Download PDF]

  45. Dworkin J. and Losick R. (2001) Linking nutritional status to gene activation and development. Genes Dev. 15: 1051-1055.