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Your search keyword '"Undheim EAB"' showing total 2 results
Start Over Author "Undheim EAB" Publisher natl acad sciences
2 results on '"Undheim EAB"'

1. Structural venomics reveals evolution of a complex venom by duplication and diversification of an ancient peptide-encoding gene

Author

Pineda SS, Chin YK-Y, Undheim EAB, Senff S, Mobli M, Dauly C, Escoubas P, Nicholson GM, Kaas Q, Guo S, Herzig V, Mattick JS, and King GF

Subjects
Proteomics, Protein Conformation, Diptera, Gene Expression Profiling, Australia, Spider Venoms, Spiders, complex mixtures, Mass Spectrometry, Arthropod Proteins, Evolution, Molecular, Animals, Female, Disulfides, Peptides, Phylogeny
Abstract

Spiders are one of the most successful venomous animals, with more than 48,000 described species. Most spider venoms are dominated by cysteine-rich peptides with a diverse range of pharmacological activities. Some spider venoms contain thousands of unique peptides, but little is known about the mechanisms used to generate such complex chemical arsenals. We used an integrated transcriptomic, proteomic, and structural biology approach to demonstrate that the lethal Australian funnel-web spider produces 33 superfamilies of venom peptides and proteins. Twenty-six of the 33 superfamilies are disulfide-rich peptides, and we show that 15 of these are knottins that contribute >90% of the venom proteome. NMR analyses revealed that most of these disulfide-rich peptides are structurally related and range in complexity from simple to highly elaborated knottin domains, as well as double-knot toxins, that likely evolved from a single ancestral toxin gene.

Published
2020

2. Selective NaV1.1 activation rescues Dravet syndrome mice from seizures and premature death

Author

Richards, KL, Milligan, CJ, Richardson, RJ, Jancovski, N, Grunnet, M, Jacobson, LH, Undheim, EAB, Mobli, M, Chow, CY, Herzig, V, Csoti, A, Panyi, G, Reid, CA, King, GF, Petrou, S, Richards, KL, Milligan, CJ, Richardson, RJ, Jancovski, N, Grunnet, M, Jacobson, LH, Undheim, EAB, Mobli, M, Chow, CY, Herzig, V, Csoti, A, Panyi, G, Reid, CA, King, GF, and Petrou, S

Abstract

Dravet syndrome is a catastrophic, pharmacoresistant epileptic encephalopathy. Disease onset occurs in the first year of life, followed by developmental delay with cognitive and behavioral dysfunction and substantially elevated risk of premature death. The majority of affected individuals harbor a loss-of-function mutation in one allele of SCN1A, which encodes the voltage-gated sodium channel NaV1.1. Brain NaV1.1 is primarily localized to fast-spiking inhibitory interneurons; thus the mechanism of epileptogenesis in Dravet syndrome is hypothesized to be reduced inhibitory neurotransmission leading to brain hyperexcitability. We show that selective activation of NaV1.1 by venom peptide Hm1a restores the function of inhibitory interneurons from Dravet syndrome mice without affecting the firing of excitatory neurons. Intracerebroventricular infusion of Hm1a rescues Dravet syndrome mice from seizures and premature death. This precision medicine approach, which specifically targets the molecular deficit in Dravet syndrome, presents an opportunity for treatment of this intractable epilepsy.

Published
2018

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