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Biologist who found unexpected power in protein folding.

A Sup35 chimaera that traverses the transmission barrier between two yeast species possesses the critical sequence elements from both. This chimaera is used to show that the influence of environment and mutations on the formation of species-specific strains is driven by selective recognition of either sequence element. Thus, critical aspects of prion conversion are enciphered by subtle differences between small, highly specific recognition elements.

Previously thought to be rare laboratory artefacts or diseases of yeast, prions are actually found in one third of 700 wild strains; the prions give their hosts beneficial traits that can be transmitted epigenetically to the next generation, and then fixed in the genome.

Susan Lindquist and colleagues report a genetic interaction between α-synuclein and the ortholog of human ATP13A2 (PARK9) in yeast, two genes that when mutated cause Parkinson's disease. They further show that yeast PARK9 protects cells from manganese toxicity, a known environmental risk factor for Parkinson's disease.

The transcriptional activator SWI was recently shown to propagate as a prion in yeast. Cyc8, a co-repressor that regulates a similar set of genes as SWI, also propagates as a prion, suggesting a link between chromatin remodelling and cytoplasmic inheritance of prion traits.

How much transgenerational epigenetic inheritance takes place, and what impact does this have on organisms? We asked five leading researchers — working on key model organisms and on human disease — for their views.

Luminescent conjugated polymers (LCPs) bind to prion aggregates and emit different fluorescent spectra depending on their binding conformation. As such, they are promising tools for investigating the biophysical basis of prion strains.

Mitochondrial energy metabolism regulates proteotoxic stress tolerance, exposing a newly discovered sensitivity to the small molecule elesclomol, which induces FDX1-mediated, copper-dependent cell death.

A potent inhibitor of the conditionally essential mitochondrial phosphate carrier protein Mir1 in the fungi Candida albicans diminishes mitochondrial oxygen consumption and causes dramatic changes in concentrations of citrate and succinate.

Four recent studies on the molecular architecture of amyloid fibrils made from different prion protein segments suggest commonalities among these fibrils. These studies also shed light on the structural distinctions between prion strains and the mechanism of fiber formation.

Two main features make budding yeast a key model organism for eukaryotic biology: its amenability to analysis and its conserved genome and cellular biology. Here, the authors highlight the valuable mechanistic insights into the cell-autonomous mechanisms of neurodegeneration that are emerging from studies inSaccharomyces cerevisiae.

The sensitivity of chaperones to the stability of client proteins is used for kinome-wide profiling of kinase inhibitors.

The chaperone Hsp90 is a potential target for the development of drugs against fungal pathogens. Here the authors determine the structure of the Hsp90 nucleotide-binding ___domain from Candida albicans, which they use to design an inhibitor and demonstrate its selectivity for the fungal enzyme, both biochemically and in cells.

Despite the increasing prevalence of neurodegenerative diseases in our ageing population, disease-modifying therapies remain elusive. As the mechanisms underlying neurodegeneration are poorly understood, these diseases are not especially amenable to target-based drug screening strategies. Here, Khurana et al. present phenotypic screening as an alternative drug discovery approach, and discuss how insights from a simple eukaryote, baker's yeast, are driving research in patient-derived neurons.

Tumbarello, Buss and colleagues report that the motor protein myosin VI has an important role in autophagosome maturation. They show that myosin VI binds to autophagy adaptors to mediate delivery of endocytic cargo and endosomal membrane to autophagosomes, and promote autophagosome–lysosome fusion.

Amyloid fibrils feature in many human diseases and in epigenetic memory, but understanding their molecular structure has been difficult. Now, through a combination of optical trapping and fluorescent imaging to examine amyloid fibrils of the yeast prion protein Sup35, the unexpected unfolding of individual subdomains has been detected, suggesting strong noncovalent interactions maintain the fibril even if individual monomers unfold.

Ernest Fraenkel and colleagues present ResponseNet, a method used to integrate analysis of genetic and transcriptional datasets, and its application characterizing yeast cellular responses to alpha-synuclein toxicity.

The proteome of the malarial parasite Plasmodium falciparum has an overabundance of aggregation-prone asparagine repeat-containing proteins. Muralidharan et al. show that PlasmodiumHsp110 protein potently prevents aggregation of asparagine-rich proteins, thereby allowing the parasite to survive febrile episodes.

An amphotericin antifungal that is less toxic to human cells due to its increased capacity for binding the fungal ergosterol over the human cholesterol can still evade resistance mechanisms, challenging the resistance-toxicity yin-yang of antimicrobials.

Sequencing the nuclear genomes of Guillardia theta and Bigelowiella natans, transitional forms in the endosymbiotic acquisition of photosynthesis by engulfment of certain eukaryotic algae, reveals unprecedented alternative splicing for a single-celled organism (B. natans) and extensive genetic and biochemical mosaicism, shedding light on why nucleomorphs persist in these species but not other algae.

Changes to protein interactomes as a result of mutations to the bait protein or addition of a pharmacological inhibitor are robustly monitored with affinity purification coupled with data-independent acquisition–based mass spectrometry and an automated data analysis pipeline. Also in this issue, Collins et al. describe a similar method.

Thermostable enzymes are used for a range of industrial processes, including biofuel production. Berka et al. report the genome sequences of two thermophilic eukaryotic fungi with enzymes that operate at the elevated temperatures needed to digest biomass and prepare many biochemicals.

Gaglia et al. show, using single-cell imaging and analysis in human tumours, that phase transition of heat-shock factor 1 (HSF1) to form intranuclear stress bodies mediates cell-fate decisions underlying cell survival or death.

The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.

Much remains to be learned about the biology of mushrooms, which are an important source of food as well as secondary metabolites and enzymes of biotechnological importance. Ohm et al. report the sequence of the genetically tractable species Schizophyllum commune and identify genes involved in the formation of fruiting bodies and the degradation of lignocellulose.

A method based on the split-ubiquitin assay monitors interactions between membrane proteins within human cells.