Performance of basic research on microbial molecular genetics, cell biology and physiology.
6 CENTER DR Room 3B314, MSC 2785
Bethesda Md 20892-2785
For FedEx use:
Bethesda Md 20892
Michael Cashel was born in Worthington, MN (1937), BA in biology/chemistry at Amherst College working on radiological target size of Salmonella typhimurium phage 22 transduction, then M.D. in 1963 at CRU School of Medicine working with Dr. Frederick Robbins on tissue culture genetics followed by studies in USPHS of Bacillus subtilis sporulation and DNA crosslinking with Dr. Ernst Freese at NIH. Then on a USPHS training grant I went to the University of Washington and received a Ph.D. in Genetics with Dr. Jonathan Gallant in 1968. In the course of this work discovered a spot on thin layer chromatograms that appeared during the operation of E.coli stringent response to amino acid starvation. I returned to NIH in 1967 to work out the composition of material, which turned out to be nucleotide analogs of GDP and GTP with the ribosyl 3' hydroxyl derivatized with pyrophosphates [(p)ppGpp]. Subsequent studies led to understanding the molecular basis of their regulation of these nucleotides as generalized sensors of stress and subtle perturbations of carbon and amino acid biosynthesis metabolism which function to curtail cellular activities that are superfluous during times of stress including nutritional deficiency. These signals accomplish this through global effects on gene expression at the level of direct interactions with the RNA transcriptional apparatus rather than processes mediated by DNA recognition proteins, as is the case for classical nucleotide second messengers such as cAMP. The ability to respond to the stress of environmental changes is common to all cells in biology whereas the (p)ppGpp regulatory nucleotides are currently known to have similar regulatory functions in bacteria and plants. Currently there are hints that that this regulatory system may extend to animals in a modified form, which are currently being pursued.
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
Rhee HW, Lee CR, Cho SH, Song MR, Cashel M, Choy HE, Seok YJ, Hong JI. Selective fluorescent chemosensor for the bacterial alarmone (p)ppGpp. J Am Chem Soc. 2008 Jan 23;130(3):784-5. Epub 2008 Jan 1.PMID: 18166051
Potrykus K, Vinella D, Murphy H, Szalewska-Palasz A, D'Ari R, Cashel M. Antagonistic regulation of Escherichia coli ribosomal RNA rrnB P1 promoter activity by GreA and DksA. J Biol Chem. 2006 Jun 2;281(22):15238-48. Epub 2006 Apr 5.PMID: 16597620