Biology subjects

Banks, P.

Publications and source records attributed to Banks, P..

4 recordsLinked to original sources

bioRxiv2022

Mircubactin B rescues the lethal effect of cell wall biosynthesis mutations in Bacillus subtilis.

Growth of most rod-shaped bacteria is accompanied by the insertion of new peptidoglycan into the cylindrical cell wall. This insertion, which helps maintain and determine the shape of the cell, is guided by a complex protein machinery called the rod complex or elongasome. Although most of the proteins in this complex are essential under normal growth conditions, cell viability can be rescued, for reasons that are not understood, by the presence of a high (mM) Mg2+ concentration. We screened for natural product compounds that could rescue the growth of mutants affected in rod-complex function. By screening >2,000 extracts from a diverse collection of actinobacteria, we identified a new compound, mirubactin B, related to the known iron siderophore mirubactin A, which rescued growth in the low micromolar range, and this activity was confirmed by synthesising mirubactin B. The compound also displayed toxicity at higher concentrations, and this effect appears related to iron homeostasis. However, several lines of evidence suggest that the mirubactin B rescuing activity is not due simply to iron sequestration. The results demonstrate a novel antibacterial compound and add to growing evidence that bacterial siderophores have a range of activities beyond simple iron sequestration.

microbiology↗

bioRxiv2019

Parallel siRNA screens to identify kinase and phosphatase modulators of NF-κB activity following DNA damage

DNA damage, such as that experienced by people undergoing chemotherapy, can directly activate NF-{kappa}B signalling which in turn can lead to resistance to genotoxic stress. NF-{kappa}B signalling is highly regulated by phosphorylation, but the enzymes required for these processes remain largely unknown. Identifying those enzymes responsible for regulating NF-{kappa}B activity may yield attractive targets for new clinical therapies, as well as provide the basis for better understanding of signalling network crosstalk. Here we present datasets from two independent RNAi screens using a stable NF-{kappa}B reporter U2OS cell line with the aim of identifying enzymes that alter NF-{kappa}B activity in response to DNA damage following etoposide and ionising radiation treatments. Although we observed high internal validity and specificity to NF-{kappa}B modulation within the screens, there was a striking dissimilarity between the results of the two different screens. These data therefore provide a cautionary lesson regarding the use of RNAi screening but also provide new candidates for kinase and phosphatase regulation of NF-{kappa}B activity in response to genotoxic stress.

cell biology↗

bioRxiv2018

Discovery of volatile biomarkers of Parkinsons disease from sebum

Parkinsons disease (PD) is a progressive, neurodegenerative disease that presents with significant motor symptoms, for which there is no diagnostic test (1-3). We have serendipitously identified a hyperosmic individual, a Super Smeller that can detect PD by odor alone, and our early pilot studies have indicated that the odor was present in the sebum from the skin of PD subjects(4). Here, we have employed an unbiased approach to investigate the volatile metabolites of sebum samples obtained non-invasively from the upper back of 64 participants in total (21 controls and 43 PD subjects). Our results, validated by an independent cohort, identified a distinct volatiles-associated signature of PD, including altered levels of perillic aldehyde and eicosane, the smell of which was then described as being highly similar to the scent of PD by our Super Smeller.\n\n1 sentence summaryMetabolomics identifies volatile odorous compounds from patient sebum that associate with the smell of Parkinsons.

neuroscience↗

bioRxiv2018

Vps74 connects the Golgi apparatus and telomeres in Saccharomyces cerevisiae

In mammalian cell culture, the Golgi apparatus fragment upon DNA damage. GOLPH3, a Golgi component, is a phosphorylation target of DNA-PK after DNA damage and contributes to Golgi fragmentation. The function of the yeast (Saccharomyces cerevisiae) ortholog of GOLPH3, Vps74, in the DNA damage response has been little studied, although genome-wide screens suggested a role at telomeres. In this study we investigated the role of Vps74 at telomeres and in the DNA damage response. We show that Vps74 decreases the fitness of telomere defective cdc13-1 cells and contributes to the fitness of yku70{Delta} cells. Importantly, loss of Vps74 in yku70{Delta} cells exacerbates the temperature dependent growth defects of these cells in a Chk1 and Mec1-dependent manner. Furthermore, Exo1 reduces fitness of vps74{Delta} yku70{Delta} cells suggesting that ssDNA contributes to the fitness defects of vps74{Delta} yku70{Delta} cells. Systematic genetic interaction analysis of vps74{Delta}, yku70{Delta} and yku70{Delta} vps74{Delta} cells suggests that vps74{Delta} causes a milder but similar defect to that seen in yku70{Delta} cells. vps74{Delta} cells have slightly shorter telomeres and loss of VPS74 in yku70{Delta} or mre11{Delta} cells further shortens the telomeres of these cells. Interestingly, loss of Vps74 leads to increased levels of Stn1, a partner of Cdc13 in the CST telomere capping complex. Overexpression of Stn1 was previously shown to cause telomere shortening, suppression of cdc13-1 and enhancement of yku70{Delta} growth defects, suggesting that increased levels of Stn1 may be the route by which Vps74 affects telomere function. These results establish Vps74 as a novel regulator of telomere biology.

genetics↗