Biology subjects

Cullum, R.

Publications and source records attributed to Cullum, R..

3 recordsLinked to original sources

bioRxiv2023

Bacterial Diversity and Chemical Ecology of Natural Product-Producing Bacteria from Great Salt Lake Sediment

Great Salt Lake (GSL), located northwest of Salt Lake City, UT, is the largest terminal lake in the United States. While the average salinity of seawater is [~]3.3%, the salinity in GSL ranges between 5-28%. In addition to being a hypersaline environment, GSL also contains toxic concentrations of heavy metals, such as arsenic, mercury, and lead. The extreme environment of GSL makes it an intriguing subject of study, both for its unique microbiome and its potential to harbor novel natural product-producing bacteria, which could be used as resources for the discovery of biologically active compounds. Though work has been done to survey and catalogue bacteria found in GSL, the Lakes microbiome is largely unexplored, and little-to-no work has been done to characterize the natural product potential of GSL microbes. Here, we investigate the bacterial diversity of two important regions within GSL, describe the first genomic characterization of Actinomycetota isolated from GSL sediment, including the identification of a new Saccharomonospora species, and provide the first survey of the natural product potential of GSL bacteria.

ecology↗

bioRxiv2022

Nanoscaled discovery of a shunt rifamycin from Salinispora arenicola using a three-colour GFP-tagged Staphylococcus aureus macrophage infection assay.

Antimicrobial resistance has emerged as an urgent global public health threat, and development of novel therapeutics for treating infections caused by multi-drug resistant bacteria is urgent. Staphylococcus aureus is a major human and animal pathogen, responsible for high levels of morbidity and mortality worldwide. The intracellular survival of S. aureus in macrophages contributes to immune evasion, dissemination, and resilience to antibiotic treatment. Here, we present a confocal fluorescence imaging assay for monitoring macrophage infection by GFP-tagged Staphylococcus aureus as a front-line tool to identify antibiotic leads. The assay was employed in combination with nanoscaled chemical analyses to facilitate the discovery of a novel, active rifamycin analogue. Our findings indicate a promising new approach to the identification of anti-microbial compounds with macrophage intracellular activity. The novel antibiotic identified here may represent a useful addition to our armoury in tackling the silent pandemic of antimicrobial resistance.

cell biology↗

bioRxiv2020

SOX9 is sufficient to drive endothelial cells towards a mesenchymal fate by altering the chromatin landscape.

The transcription factor SOX9 is expressed in multiple tissues during embryogenesis and directs developmental processes. SOX9 is activated upon endothelial-to-mesenchymal transition (EndMT) in the developing heart, but its role in regulating this process is less clear. Using human umbilical vein endothelial cells as an EndMT model, we show that SOX9 expression alone is sufficient to activate mesenchymal enhancers and steer endothelial cells towards a mesenchymal fate. By genome-wide mapping of the chromatin landscape, we show that SOX9 acts as a pioneer transcription factor, having the ability to open chromatin and lead to deposition of active histone marks at a specific subset of previously silent enhancers, guided by SOX motifs and H2A.Z enrichment. This leads to a switch in enhancer activity states resulting in activation of mesenchymal genes and concurrent suppression of endothelial genes to drive EndMT. Moreover, we show that SOX9 chromatin binding is dynamic, but induces stable changes in the chromatin landscape. Our data also show widespread SOX9 chromatin scanning in silent chromatin that is not associated with SOX motifs or H2A.Z enrichment. Our study highlights the crucial developmental role of SOX9 and provides new insight into key molecular functions of SOX9 in the chromatin landscape and mechanisms of EndMT. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=94 SRC="FIGDIR/small/293993v2_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@1248576org.highwire.dtl.DTLVardef@b6420forg.highwire.dtl.DTLVardef@1aaffc5org.highwire.dtl.DTLVardef@17de585_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗