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Fairman, R.

Publications and source records attributed to Fairman, R..

3 recordsLinked to original sources

Genipin Alleviates Sleep Deficiencies Caused by α-Synuclein Toxicity in a Drosophila melanogaster Model of Parkinsons Disease

Parkinsons disease is predominantly characterized by dopaminergic neurodegeneration linked to toxic aggregation of -synuclein. Genipin, a bioactive iridoid, was previously shown to improve the motility and survival deficits caused by pan-neuronal expression of native -synuclein in a transgenic Drosophila melanogaster model system. We show that expression of -synuclein causes sleep deficits and that genipin treatment rescued these sleep deficits, increasing total sleep and consolidating nighttime sleep relative to untreated -synuclein-expressing fruit flies. Our findings extend genipins protective profile in Drosophila melanogaster and highlight sleep regulation as an additional phenotype responsive to -synuclein-targeted interventions.

neuroscience↗

A Phosphopantetheinyl Transferase from Dictyobacter vulcani sp. W12 Expands the Combinatorial Biosynthetic Toolkit

The value of microbial natural product pathways extends beyond the chemicals they produce, as the enzymes they encode can be harnessed as biocatalysts. Microbial type II polyketide synthases (PKSs) are particularly noteworthy, as these enzyme assemblies produce complex polyaromatic pharmacophores. Combinatorial biosynthesis with type II PKSs has been described as a promising route for accessing never-before-seen bioactive molecules, but this potential is stymied in part by the lack of functionally compatible non-cognate proteins across type II PKS systems. Acyl carrier proteins (ACPs) are central to this challenge, as they shuttle reactive intermediates and malonyl building blocks between the other type II PKS domains during biosynthesis. Activating ACPs to their holo state via the phosphopantetheinyl transferase (PPTase)-catalyzed installation of a coenzyme A (CoA)-derived phosphopantetheine (Ppant) arm is critical to effectively study and strategically engineer type II PKSs, but not all ACPs can be activated using conventional PPTases. Here, we report the discovery of a previously unexplored non-actinobacterial PPTase from Dictyobacter vulcani sp. nov. W12 (vulcPPT). We explored its compatibility with both native and non-native ACPs, observing that vulcPPT activated all ACPs tested in this study, including a non-cognate, non-actinobacterial ACP which cannot be activated by the prototypical broad substrate PPTases AcpS and Sfp. Strategic optimization of phosphopantetheinylation reaction conditions increased apo to holo conversion. In addition to identifying a promising new promiscuous PPTase, this work establishes a road map for further investigation of PPTase compatibility and increases access to functional synthase components for use in combinatorial biosynthesis.

biochemistry↗

Invasive species-driven trophic cascades: Are cane toads indirectly contributing to small mammal collapses across tropical Australia?

Apex predators are fundamentally important in regulating many ecosystems, and perturbations of their populations are frequently implicated in ecosystem declines or collapses. In considering small mammal declines in northern Australia, most attention has focused on interactions between a mammalian apex predator--the dingo Canis dingo--and a meso-predator, the feral cat--Felis catus. Little consideration has been given to the possible implications of changed reptilian predator assemblages resulting from invasion by a toxic anuran invader, the cane toad (Rhinella marina), on small mammals. We used reptile removal records from licenced reptile catchers in three widely spaced towns in the savannas of northern Australia to explore potential impacts of toads on apex and meso-predatory snakes and large lizards. In addition, simultaneous fauna survey data from one town with reptile removal records, coinciding with toad invasion, were used to identify cascading impacts through the savanna ecosystem. Intervention analyses revealed empirical linkages between toad invasion, apex predator declines, meso-predator increases and declines of small mammals and other prey groups. Based on the timing and strength of intervention we postulate a novel conceptual model linking recent mammal declines with trophic cascades following toad invasion, where the loss of large, anurophagous (toad-eating) reptilian apex predators allowed increases in mammal-eating meso-predatory snakes. The conceptual model is discussed in relation to prevailing hypotheses regarding northern Australias dramatic small mammal declines. Future studies will need to quantify these putative interactions and test their comparative importance so that appropriate management can be implemented to stem the ongoing losses of mammal fauna.

ecology↗