Publications by authors named "Gary Andrew Bradshaw"

Article Synopsis
  • Current treatments for advanced prostate cancer mainly focus on androgen receptor pathways, but issues like castration-resistant prostate cancer (CRPC) pose significant challenges.
  • The study introduces BSJ-5-63, a new triple degrader that targets specific cyclin-dependent kinases (CDK12, CDK7, CDK9) to reduce both DNA repair genes and androgen receptor signaling, enhancing treatment efficacy.
  • BSJ-5-63 creates a lasting "BRCAness" state, allowing for effective sequential therapy with PARP inhibitors while reducing drug-related side effects and resistance, potentially benefiting a wide range of CRPC patients.
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In bacteria, algae, fungi, and plant cells, the wall must expand in concert with cytoplasmic biomass production, otherwise cells would experience toxic molecular crowdingor lyse. But how cells achieve expansion of this complex biomaterial in coordination with biosynthesis of macromolecules in the cytoplasm remains unexplained, although recent works have revealed that these processes are indeed coupled. Here, we report a striking increase of turgor pressure with growth rate in , suggesting that the speed of cell wall expansion is controlled via turgor.

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Central carbon metabolism is highly conserved across microbial species, but can catalyze very different pathways depending on the organism and their ecological niche. Here, we study the dynamic reorganization of central metabolism after switches between the two major opposing pathway configurations of central carbon metabolism, glycolysis, and gluconeogenesis in Escherichia coli, Pseudomonas aeruginosa, and Pseudomonas putida. We combined growth dynamics and dynamic changes in intracellular metabolite levels with a coarse-grained model that integrates fluxes, regulation, protein synthesis, and growth and uncovered fundamental limitations of the regulatory network: After nutrient shifts, metabolite concentrations collapse to their equilibrium, rendering the cell unable to sense which direction the flux is supposed to flow through the metabolic network.

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