Volume 12 Issue 6, June 2016

Scientific convergence is a common theme of modern research, but undergraduate chemistry is commonly taught as an isolated discipline. Here we discuss curricular updates at three different institutions that are independently seeking to increase convergence in introductory chemistry courses.

A small molecule has been identified that can mitigate the progression of an inherited form of deafness in transgenic mice by stabilizing mutant clarin-1, an essential component of a multimolecular complex of the mechanotransduction apparatus of hair cells in the inner ear.

Phosphoglycerate dehydrogenase (PHGDH) is an enzyme of serine biosynthesis overexpressed in various types of cancer. A new series of PHGDH inhibitors selectively block proliferation of PHGDH-dependent cancer cells and reveal an unexpected role of serine biosynthesis in coordinating one-carbon metabolism.

Iron–sulfur metalloproteins are critical for electron transfer in bacterial metabolism, but most crystal structures are insufficient for their in-depth study. Now, acquisition of an iron–sulfur protein structure at ultra-high resolution enables detailed visualization of its electron distribution.

A synthetic biochemistry approach optimizes a glucose breakdown pathway to produce acetyl-CoA as a building block for polyhydroxybutyrate bioplastic production in the test tube.

Crotonylated lysine residues within histones are linked to transcriptional activation in a process involving histone mark ‘reader’ proteins. Crystallographic analysis of the YEATS domain of the Taf14 protein reveals a mode of crotonylated histone mark recognition via a π-sandwich motif.

The attachment of a nuclear export sequence to the blue light-sensitive LOV2 domain mediates rapid and reversible protein export of the ubiquitin ligase Bre1 with light exposure, resulting in changes in histone ubiquitylation and methylation.

Monitoring new fluorescent ganglioside analogs at a single-molecule level suggests that gangliosides associate dynamically with GPI-anchored protein monomers, transient homodimer rafts, and clustered signaling rafts in a cholesterol-dependent manner.

A chemical genetic approach to localize human Polo-like kinase 1 (Plk1) to distinct regions along the kinetochore–centromere axis combined with phosphoproteomic analysis reveals the presence of distinct Plk1 pools to mediate chromosomal segregation.

Analysis of orphan nonribosomal peptide synthetase–like gene clusters from Aspergillus fumigatus identified a gene cluster responsible for the biosynthesis of fumisoquin isoquinoline alkaloids by amino acid condensation and subsequent tailoring steps reminiscent of plant biosynthetic pathways.

Identification of minimal functional CRY2–CIB1 domains and mutations that increased CRY2 photocycle lifetimes combined with the development of an improved photoactivable Cre recombinase enables efficient gene editing.

An optogenetic approach using the CRY2−CIB1 heterodimerization system results in light-mediated cross-linking and aggregation of different Rab GTPases, disrupting membrane and endosomal trafficking in various cell types.

A fluorescent sensor combining a mutated form of the 2-Cys peroxiredoxin Tsa2 unable to undergo thioredoxin-mediated reduction with a redox-sensitive GFP protein allows real-time detection of baseline hydrogen peroxide levels in yeast cells.

A small molecule identified from high-throughput screening and optimization specifically stabilizes a disease-linked CLRN1 protein, delivering it to its site of action at the plasma membrane and preserving hearing in a new mouse model for Usher syndrome type III.

A quantitative high-throughput screen identified an inhibitor of phosphoglycerate dehydrogenase (PHGDH), a key enzyme for serine synthesis. This inhibitor limits one-carbon unit availability for nucleotide synthesis.

A new technique called click-EM uses singlet oxygen-generating fluorescent dyes and correlated light microscopy and EM to metabolically label and visualize nucleic acids and lipids at high resolution in cultured neurons and cells.