Gisela Storz | |
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Gisela Storz is a microbiologist at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at the National Institutes of Health (NIH). She is a member of the National Academy of Sciences.
Gisela "Gigi" Storz received a B.A. in biochemistry in 1984 from University of Colorado Boulder. She completed her Ph.D. in biochemistry from University of California, Berkeley in the laboratory of Bruce Ames in 1988, where she discovered that OxyR senses hydrogen peroxide stress in Escherichia coli oxidation response. She trained briefly as a postdoctoral fellow at the National Cancer Institute with Sankar Adhya in 1989 and at Harvard Medical School with Frederick M. Ausubel from 1989 to 1991. [1] She joined the National Institute of Child Health and Human Development at NIH in 1991 and is currently head of the Section on Environmental Gene Regulation.
Storz's research interests include the characterization of small non-coding RNA and small proteins of 50 amino acids or less. [2] [3] An early focus of her research was the study of redox-sensitive transcription factors and the bacterial and yeast responses to oxidative stress. She discovered that the activity of the Escherichia coli transcription factor OxyR, now a paradigm for other redox-sensitive proteins, is regulated by reversible disulfide bond formation and elucidated how disulfide bond formation controls the nuclear localization of the Saccharomyces cerevisiae transcription factor Yap1. As a result of her group's serendipitous detection of the OxyS RNA, one of the first small regulatory RNAs to be discovered, attention shifted to the genome-wide identification and characterization of small regulatory RNAs in the model organism Escherichia coli . Work on small RNAs in Dr. Storz's lab revealed that the RNA chaperone Hfq stimulates the pairing of the majority of the small RNAs with mRNA targets and that small RNAs are integral to most regulatory circuits in bacteria. While identifying these small RNAs, her lab discovered that some of these small RNAs encode small proteins that had previously been overlooked because they are not detected in many traditional biochemical assays and the corresponding genes are poorly annotated. Her research group demonstrated that one such small protein, AcrZ, binds to the multidrug efflux pump protein AcrB to affect its ability to export certain classes of antibiotics. The Storz lab currently seeks to identify and to characterize the function of other small proteins from Escherichia coli .
The gene rpoS encodes the sigma factor sigma-38, a 37.8 kD protein in Escherichia coli. Sigma factors are proteins that regulate transcription in bacteria. Sigma factors can be activated in response to different environmental conditions. rpoS is transcribed in late exponential phase, and RpoS is the primary regulator of stationary phase genes. RpoS is a central regulator of the general stress response and operates in both a retroactive and a proactive manner: it not only allows the cell to survive environmental challenges, but it also prepares the cell for subsequent stresses (cross-protection). The transcriptional regulator CsgD is central to biofilm formation, controlling the expression of the curli structural and export proteins, and the diguanylate cyclase, adrA, which indirectly activates cellulose production. The rpoS gene most likely originated in the gammaproteobacteria.
GadY RNA is a non-coding RNA. The GadY gene is located on between and on the opposite strand to the GadX and GadW genes. GadY can form base pairs with the 3' UTR of its target mRNA gadX, this pairing is thought to confer increased stability to the transcript, allowing accumulation of gadX and therefore increased expression of downstream acid resistance genes. The GadY gene produces three overlapping transcripts that differ in length. The long form is 105 nucleotides in length and two processed versions are 59 and 90 nucleotides in length. It has been shown that all three forms of GadY bind to the Hfq protein.
The OmrA-B RNA gene family is a pair of homologous OmpR-regulated small non-coding RNA that was discovered in E. coli during two large-scale screens. OmrA-B is highly abundant in stationary phase, but low levels could be detected in exponentially growing cells as well. RygB is adjacent to RygA a closely related RNA. These RNAs bind to the Hfq protein and regulate gene expression by antisense binding. They negatively regulate the expression of several genes encoding outer membrane proteins, including cirA, CsgD, fecA, fepA and ompT by binding in the vicinity of the Shine-Dalgarno sequence, suggesting the control of these targets is dependent on Hfq protein and RNase E. Taken together, these data suggest that OmrA-B participates in the regulation of outer membrane composition, responding to environmental conditions.
The MicC non-coding RNA is located between the ompN and ydbK genes in E. coli. This Hfq-associated RNA is thought to be a regulator of the expression level of the OmpC porin protein, with a 5′ region of 22 nucleotides potentially forming an antisense interaction with the ompC mRNA. Along with MicF RNA this family may act in conjunction with EnvZ-OmpR two-component system to control the OmpF/OmpC protein ratio in response to a variety of environmental stimuli. The expression of micC was shown to be increased in the presence of beta-lactam antibiotics.
OxyS RNA is a small non-coding RNA which is induced in response to oxidative stress in Escherichia coli. This RNA acts as a global regulator to activate or repress the expression of as many as 40 genes, by an antisense mechanism, including the fhlA-encoded transcriptional activator and the rpoS-encoded sigma(s) subunit of RNA polymerase. OxyS is bound by the Hfq protein, that increases the OxyS RNA interaction with its target messages. Binding to Hfq alters the conformation of OxyS. The 109 nucleotide RNA is thought to be composed of three stem-loops.
The RprA RNA gene encodes a 106 nucleotide regulatory non-coding RNA. Translational regulation of the stationary phase sigma factor RpoS is mediated by the formation of a double-stranded RNA stem-loop structure in the upstream region of the rpoS messenger RNA, occluding the translation initiation site.
RybB is a small non-coding RNA was identified in a large scale screen of Escherichia coli. The function of this short RNA has been studied using a transcriptomic approach and kinetic analyses of target mRNA decay in vivo. RybB was identified as a factor that selectively accelerates the decay of multiple major omp mRNAs upon induction of the envelope stress response. This RNA has been shown to bind to the Hfq protein.
The SdsR/RyeB RNA is a non-coding RNA that was identified in a large scale screen of E. coli. The exact 5′ and 3′ ends of this RNA are uncertain. This RNA overlaps the SraC/RyeA RNA on the opposite strand suggesting that the two may act in a concerted manner. It is transcribed by general stress factor σs and is most highly expressed in stationary phase. SdsR/RyeB RNA interacts with Hfq.
The CyaR RNA non-coding RNA was identified in a large scale screen of Escherichia coli and was called candidate 14. The exact 5′ and 3′ ends of this RNA are uncertain. This gene lies between yegQ and orgK in E. coli. This small RNA was shown to be bound by the Hfq protein. This RNA has been renamed as CyaR for. It has been shown that the CyaR RNA acts as a repressor of the porin OmpX. It has also been shown that cyaR expression is tightly controlled by the cyclic AMP receptor protein, CRP.
RyhB RNA is a 90 nucleotide RNA that down-regulates a set of iron-storage and iron-using proteins when iron is limiting; it is itself negatively regulated by the ferric uptake repressor protein, Fur.
Spot 42 (spf) RNA is a regulatory non-coding bacterial small RNA encoded by the spf gene. Spf is found in gammaproteobacteria and the majority of experimental work on Spot42 has been performed in Escherichia coli and recently in Aliivibrio salmonicida. In the cell Spot42 plays essential roles as a regulator in carbohydrate metabolism and uptake, and its expression is activated by glucose, and inhibited by the cAMP-CRP complex.
The MicA RNA is a small non-coding RNA that was discovered in E. coli during a large scale screen. Expression of SraD is highly abundant in stationary phase, but low levels could be detected in exponentially growing cells as well.
In molecular biology the ArcZ RNA is a small non-coding RNA (ncRNA). It is the functional product of a gene which is not translated into protein. ArcZ is an Hfq binding RNA that functions as an antisense regulator of a number of protein coding genes.
The sroB RNA is a non-coding RNA gene of 90 nucleotides in length. sroB is found in several Enterobacterial species but its function is unknown. SroB is found in the intergenic region on the opposite strand to the ybaK and ybaP genes. SroB is expressed in stationary phase. Experiments have shown that SroB is a Hfq binding sRNA.
The Hfq protein encoded by the hfq gene was discovered in 1968 as an Escherichia coli host factor that was essential for replication of the bacteriophage Qβ. It is now clear that Hfq is an abundant bacterial RNA binding protein which has many important physiological roles that are usually mediated by interacting with Hfq binding sRNA.
An Hfq binding sRNA is an sRNA that binds the bacterial RNA binding protein called Hfq. A number of bacterial small RNAs which have been shown to bind to Hfq have been characterised . Many of these RNAs share a similar structure composed of three stem-loops. Several studies have expanded this list, and experimentally validated a total of 64 Hfq binding sRNA in Salmonella Typhimurium. A transcriptome wide study on Hfq binding sites in Salmonella mapped 126 Hfq binding sites within sRNAs. Genomic SELEX has been used to show that Hfq binding RNAs are enriched in the sequence motif 5′-AAYAAYAA-3′. Genome-wide study identified 40 candidate Hfq-dependent sRNAs in plant pathogen Erwinia amylovora. 12 of them were confirmed by Northern blot.
Bacterial small RNAs (bsRNA) are small RNAs produced by bacteria; they are 50- to 500-nucleotide non-coding RNA molecules, highly structured and containing several stem-loops. Numerous sRNAs have been identified using both computational analysis and laboratory-based techniques such as Northern blotting, microarrays and RNA-Seq in a number of bacterial species including Escherichia coli, the model pathogen Salmonella, the nitrogen-fixing alphaproteobacterium Sinorhizobium meliloti, marine cyanobacteria, Francisella tularensis, Streptococcus pyogenes, the pathogen Staphylococcus aureus, and the plant pathogen Xanthomonas oryzae pathovar oryzae. Bacterial sRNAs affect how genes are expressed within bacterial cells via interaction with mRNA or protein, and thus can affect a variety of bacterial functions like metabolism, virulence, environmental stress response, and structure.
FnrS RNA is a family of Hfq-binding small RNA whose expression is upregulated in response to anaerobic conditions. It is named FnrS because its expression is strongly dependent on fumarate and nitrate reductase regulator (FNR), a direct oxygen availability sensor.
Escherichia coli contains a number of small RNAs located in intergenic regions of its genome. The presence of at least 55 of these has been verified experimentally. 275 potential sRNA-encoding loci were identified computationally using the QRNA program. These loci will include false positives, so the number of sRNA genes in E. coli is likely to be less than 275. A computational screen based on promoter sequences recognised by the sigma factor sigma 70 and on Rho-independent terminators predicted 24 putative sRNA genes, 14 of these were verified experimentally by northern blotting. The experimentally verified sRNAs included the well characterised sRNAs RprA and RyhB. Many of the sRNAs identified in this screen, including RprA, RyhB, SraB and SraL, are only expressed in the stationary phase of bacterial cell growth. A screen for sRNA genes based on homology to Salmonella and Klebsiella identified 59 candidate sRNA genes. From this set of candidate genes, microarray analysis and northern blotting confirmed the existence of 17 previously undescribed sRNAs, many of which bind to the chaperone protein Hfq and regulate the translation of RpoS. UptR sRNA transcribed from the uptR gene is implicated in suppressing extracytoplasmic toxicity by reducing the amount of membrane-bound toxic hybrid protein.
Oxidation response is stimulated by a disturbance in the balance between the production of reactive oxygen species and antioxidant responses, known as oxidative stress. Active species of oxygen naturally occur in aerobic cells and have both intracellular and extracellular sources. These species, if not controlled, damage all components of the cell, including proteins, lipids and DNA. Hence cells need to maintain a strong defense against the damage. The following table gives an idea of the antioxidant defense system in bacterial system.
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