Mike Cashel's Section on Molecular Regulation, many years ago, discovered the natural guanine nucleotide analogs ppGpp, which are now well known to function as second messengers. In bacteria and plant kingdoms, (p)ppGpp regulates global gene expression, metabolic and physiological adjustments in response to nutritional and environmental sources of stress. In bacteria, (p)ppGpp is often required for expression of virulence genes in bacterial pathogens. The Section focuses on intersections between nutritional stress, metabolism, physiology and transcription regulation with approaches that center on microbial molecular genetics, biochemistry and bioinformatics. We currently are exploring the possibility that biological diversity of (p)ppGpp synthetases and hydrolases generate new (p)ppGpp-like nucleotide regulators.
- Vinella, D., Potrykus, K., Murphy, H. & Cashel M. Effects on growth by changes of the balance between GreA, GreB, and DksA suggest mutual competition and functional redundancy in E. coli. J Bacteriol. 2012 Jan;194(2):261-73. Epub 2011 Nov 4. PMID:22056927
- Edwards, A.N., Patterson-Fortin, L.M., Vakulskas, C.A., Mercante, J.W., Potrykus, K., Vinella, D., Camacho, M.I., Fields, J.A., Thompson, S.A, Georgellis, D., Cashel, M., Babitzke, P. & Romeo, T. Circuitry linking the Csr and stringent response global regulatory systems. Mol Microbiol. 2011 Jun;80(6):1561-80. doi: 10.1111/j.1365-2958.2011.07663.x. Epub 2011 May 5.
- Potrykus K, Murphy H, Philippe N, Cashel M. ppGpp is the major source of growth rate control in E. coli. Environ Microbiol. 2010 Oct 15. doi: 10.1111/j.1462-2920.2010.02357.x. PMID: 20946586
- James TD, Cashel M, Hinton DM. A mutation within the β subunit of Escherichia coli RNA polymerase impairs transcription from bacteriophage T4 middle promoters. J Bacteriol. 2010 Nov;192(21):5580-7. Epub 2010 Aug 20.PMID: 20729353
- Potrykus K, Murphy H, Chen X, Epstein JA, Cashel M. Imprecise transcription termination within Escherichia coli greA leader gives rise to an array of short transcripts, GraL. Nucleic Acids Res. 2010 Mar;38(5):1636-51. Epub 2009 Dec 14.PMID: 20008510
- Blankschien MD, Potrykus K, Grace E, Choudhary A, Vinella D, Cashel M, Herman C. TraR, a homolog of a RNAP secondary channel interactor, modulates transcription. PLoS Genet. 2009 Jan;5(1):e1000345. Epub 2009 Jan 16.PMID: 19148274
- Harinarayanan R, Murphy H, Cashel M. Synthetic growth phenotypes of Escherichia coli lacking ppGpp and transketolase A (tktA) are due to ppGpp-mediated transcriptional regulation of tktB. Mol Microbiol. 2008 Aug;69(4):882-94. Epub 2008 Jun 4.PMID: 18532980
- Potrykus K, Cashel M. (p)ppGpp: still magical? Annu Rev Microbiol. 2008;62:35-51. Review.PMID: 18454629