Publications by authors named "Luke Simpson"

Cell-fate decisions during mammalian gastrulation are poorly understood outside of rodent embryos. The embryonic disc of pig embryos mirrors humans, making them a useful proxy for studying gastrulation. Here we present a single-cell transcriptomic atlas of pig gastrulation, revealing cell-fate emergence dynamics, as well as conserved and divergent gene programs governing early porcine, primate, and murine development.

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Article Synopsis
  • Gastrulation is a crucial phase in development, where errors can lead to major anatomical issues or congenital defects, and differences across mammalian species pose challenges for study.
  • Research using single-cell atlases and multi-species in vitro models, like gastruloids, has revealed both commonalities and variances in cell differentiation and developmental processes among species.
  • New insights highlight how intrinsic cell biochemistry and extrinsic factors, such as culture conditions, can influence embryonic development, emphasizing the need for more studies to fully understand these complex interactions.
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Pluripotency defines the unlimited potential of individual cells of vertebrate embryos, from which all adult somatic cells and germ cells are derived. Understanding how the programming of pluripotency evolved has been obscured in part by a lack of data from lower vertebrates; in model systems such as frogs and zebrafish, the function of the pluripotency genes NANOG and POU5F1 have diverged. Here, we investigated how the axolotl ortholog of NANOG programs pluripotency during development.

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Article Synopsis
  • Reversible protein phosphorylation is a key process in regulating protein function and cell signaling, and disruptions in this system are linked to various diseases.
  • The challenge in controlling phosphorylation arises because multiple kinases can phosphorylate a single substrate, making it difficult to selectively inhibit them without affecting other protein functions.
  • The AdPhosphatase system utilizes specific antibodies to direct protein phosphatases to selectively dephosphorylate target proteins, potentially paving the way for innovative drug discovery methods.
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Proteolysis-targeting chimeras (PROTACs) bring a protein of interest (POI) into spatial proximity of an E3 ubiquitin ligase, promoting POI ubiquitylation and proteasomal degradation. PROTACs rely on endogenous cellular machinery to mediate POI degradation, therefore the subcellular location of the POI and access to the E3 ligase being recruited potentially impacts PROTAC efficacy. To interrogate whether the subcellular context of the POI influences PROTAC-mediated degradation, we expressed either Halo or FKBP12 (dTAG) constructs consisting of varying localization signals and tested the efficacy of their degradation by von Hippel-Lindau (VHL)- or cereblon (CRBN)-recruiting PROTACs targeting either Halo or dTAG.

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The affinity-directed protein missile (AdPROM) system utilizes specific polypeptide binders of intracellular proteins of interest (POIs) conjugated to an E3 ubiquitin ligase moiety to enable targeted proteolysis of the POI. However, a chemically tuneable AdPROM system is more desirable. Here, we use Halo-tag/VHL-recruiting proteolysis-targeting chimera (HaloPROTAC) technology to develop a ligand-inducible AdPROM (L-AdPROM) system.

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This session contained talks on the characterization of hydrogen-enhanced corrosion of steels and nickel-based alloys, emphasizing the different observations across length scales, from atomic-scale spectrographic to macro-scale fractographic examinations.This article is part of the themed issue 'The challenges of hydrogen and metals'.

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Hydrogen in steels: discussion.

Philos Trans A Math Phys Eng Sci

July 2017

This session contained talks concerning hydrogen in steels from the point of view of simulation, experiment and industry.This article is part of the themed issue 'The challenges of hydrogen and metals'.

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