Publications by authors named "Jeanine Gezelle"

Insertion sequences are compact and pervasive transposable elements found in bacteria, which encode only the genes necessary for their mobilization and maintenance. IS200- and IS605-family transposons undergo 'peel-and-paste' transposition catalysed by a TnpA transposase, but they also encode diverse, TnpB- and IscB-family proteins that are evolutionarily related to the CRISPR-associated effectors Cas12 and Cas9, respectively. Recent studies have demonstrated that TnpB and IscB function as RNA-guided DNA endonucleases, but the broader biological role of this activity has remained enigmatic.

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Insertion sequences (IS) are compact and pervasive transposable elements found in bacteria, which encode only the genes necessary for their mobilization and maintenance. IS /IS elements undergo 'peel-and-paste' transposition catalyzed by a TnpA transposase, but intriguingly, they also encode diverse, TnpB- and IscB-family proteins that are evolutionarily related to the CRISPR-associated effectors Cas12 and Cas9, respectively. Recent studies demonstrated that TnpB-family enzymes function as RNA-guided DNA endonucleases, but the broader biological role of this activity has remained enigmatic.

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Article Synopsis
  • Researchers have developed a promising antimalarial drug lead, MBX-4055, by modifying a previously identified inhibitor to improve its bioavailability and stability while maintaining potency against malaria parasites.
  • MBX-4055 effectively enhances the permeability of host erythrocytes by targeting a specific plasmodial surface anion channel, an essential player in the parasite's nutrient acquisition.
  • The novel pyridazinone compounds show excellent absorption and tolerance in living organisms and are less likely to lead to drug resistance, making them a significant advancement in antimalarial treatment options.
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Protozoan parasites acquire essential ions, nutrients, and other solutes from their insect and vertebrate hosts by transmembrane uptake. For intracellular stages, these solutes must cross additional membranous barriers. At each step, ion channels and transporters mediate not only this uptake but also the removal of waste products.

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Malaria parasites activate a broad-selectivity ion channel on their host erythrocyte membrane to obtain essential nutrients from the bloodstream. This conserved channel, known as the plasmodial surface anion channel (PSAC), has been linked to parasite clag3 genes in P. falciparum, but epigenetic switching between the two copies of this gene hinders clear understanding of how the encoded protein determines PSAC activity.

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