A conserved role for ALG10/ALG10B and the -glycosylation pathway in the sleep-epilepsy axis.

Congenital disorders of glycosylation (CDG) comprise a class of inborn errors of metabolism resulting from pathogenic variants in genes coding for enzymes involved in the asparagine-linked glycosylation of proteins. Unexpectedly to date, no CDG has been described for , encoding the alpha-1,2-glucosyltransferase catalyzing the final step of lipid-linked oligosaccharide biosynthesis. Genome-wide association studies (GWAS) of human traits in the UK Biobank revealed significant SNP associations with short sleep duration, reduced napping frequency, later sleep timing and evening diurnal preference as well as cardiac traits at a genomic locus containing a pair of paralogous enzymes and .

Disrupted autophagy and neuronal dysfunction in C. elegans knockin models of FUS amyotrophic lateral sclerosis.

How mutations in FUS lead to neuronal dysfunction in amyotrophic lateral sclerosis (ALS) patients remains unclear. To examine mechanisms underlying ALS FUS dysfunction, we generate C. elegans knockin models using CRISPR-Cas9-mediated genome editing, creating R524S and P525L ALS FUS models.

Discriminating between sleep and exercise-induced fatigue using computer vision and behavioral genetics.

Following prolonged swimming, cycle between active swimming bouts and inactive quiescent bouts. Swimming is exercise for and here we suggest that inactive bouts are a recovery state akin to fatigue. It is known that cGMP-dependent kinase (PKG) activity plays a conserved role in sleep, rest, and arousal.

Single copy/knock-in models of ALS SOD1 in C. elegans suggest loss and gain of function have different contributions to cholinergic and glutamatergic neurodegeneration.

Mutations in Cu/Zn superoxide dismutase 1 (SOD1) lead to Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disease that disproportionately affects glutamatergic and cholinergic motor neurons. Previous work with SOD1 overexpression models supports a role for SOD1 toxic gain of function in ALS pathogenesis. However, the impact of SOD1 loss of function in ALS cannot be directly examined in overexpression models.