Publications by authors named "Monika A Sigg"

Article Synopsis
  • Phenylketonuria (PKU) arises from a deficiency in the enzyme phenylalanine hydroxylase (PAH), which impairs the conversion of phenylalanine (Phe) to tyrosine (Tyr), resulting in elevated Phe levels that can disrupt neurotransmitter function and lead to cognitive issues.
  • Research indicates that blood neurotransmitter metabolites (NTMs) can be used as indicators of brain neurotransmitter levels and show correlations between blood and brain NTMs in mice treated with PAH gene therapy.
  • In a study of participants treated with pegvaliase for PKU, blood NTMs showed significant changes: while certain metabolites decreased with treatment, levels of phenylacetylglutamine (
View Article and Find Full Text PDF

Diverse microbial ecosystems underpin life in the sea. Among these microbes are many unicellular eukaryotes that span the diversity of the eukaryotic tree of life. However, genetic tractability has been limited to a few species, which do not represent eukaryotic diversity or environmentally relevant taxa.

View Article and Find Full Text PDF

In a previous study we established forward genetics in the choanoflagellate and found that a C-type lectin gene is required for rosette development (Levin , 2014). Here we report on critical improvements to genetic screens in while also investigating the genetic basis for rosette defect mutants in which single cells fail to develop into orderly rosettes and instead aggregate promiscuously into amorphous clumps of cells. Two of the mutants, Jumble and Couscous, mapped to lesions in genes encoding two different predicted glycosyltransferases and displayed aberrant glycosylation patterns in the basal extracellular matrix (ECM).

View Article and Find Full Text PDF

Primary cilia are required for Smoothened to transduce vertebrate Hedgehog signals, but how Smoothened accumulates in cilia and is activated is incompletely understood. Here, we identify cilia-associated oxysterols that promote Smoothened accumulation in cilia and activate the Hedgehog pathway. Our data reveal that cilia-associated oxysterols bind to two distinct Smoothened domains to modulate Smoothened accumulation in cilia and tune the intensity of Hedgehog pathway activation.

View Article and Find Full Text PDF

Cilia are organelles specialized for movement and signaling. To infer when during evolution signaling pathways became associated with cilia, we characterized the proteomes of cilia from sea urchins, sea anemones, and choanoflagellates. We identified 437 high-confidence ciliary candidate proteins conserved in mammals and discovered that Hedgehog and G-protein-coupled receptor pathways were linked to cilia before the origin of bilateria and transient receptor potential (TRP) channels before the origin of animals.

View Article and Find Full Text PDF