The historical reliance of biological research on the use of animal models has sometimes made it challenging to address questions that are specific to the understanding of human biology and disease. But with the advent of human organoids — which are stem cell-derived 3D culture systems — it is now possible to re-create the architecture and physiology of human organs in remarkable detail. Human organoids

Biomolecular condensation partitions cellular contents and has important roles in stress responses, maintaining homeostasis, development and disease. Many nuclear and cytoplasmic condensates are rich in RNA and RNA-binding proteins (RBPs), which undergo liquid–liquid phase separation (LLPS). Whereas the role of RBPs in condensates has been well studied, less attention has been paid to the contribution

Increased expression of the circular RNA generated by the sulfateless gene (circSfl), and of the protein it encodes, can extend the lifespan of flies.

Complete and accurate DNA replication requires the progression of replication forks through DNA damage, actively transcribed regions, structured DNA and compact chromatin. Recent studies have revealed a remarkable plasticity of the replication process in dealing with these obstacles, which includes modulation of replication origin firing, of the architecture of replication forks, and of the functional

The SARS coronavirus 2 (SARS-CoV-2) pandemic is a global challenge, which the scientific community has tackled by mounting extensive global collaborations, combining expertise in diverse areas and applying cutting-edge techniques, to dissect mechanisms underlying coronavirus disease-19 (COVID-19) pathology. The Human Cell Atlas consortium is emerging as an important contributor to furthering this progress

Young and colleagues show that anti-cancer compounds can undergo partitioning into biomolecular condensates, affecting their activity.

The proteins extracellular signal-regulated kinase 1 (ERK1) and ERK2 are the downstream components of a phosphorelay pathway that conveys growth and mitogenic signals largely channelled by the small RAS GTPases. By phosphorylating widely diverse substrates, ERK proteins govern a variety of evolutionarily conserved cellular processes in metazoans, the dysregulation of which contributes to the cause

Human ageing is associated with high susceptibility to disease. Some aspects of ageing can be studied directly in humans and have revealed that ageing is influenced by many factors, including genetics, lifestyle, sex and socio-economic status. But identifying the factors that cause and modulate the ageing process often requires experimental interventions and modelling that can only be performed in

Building a research group in China (when you have not mastered the language) means you face the same problems as elsewhere, with an extra bit of confusion. Running a research group in China with limited knowledge of Chinese is an interesting life experience, Luis Pedro Coelho tells us.

Starting a research group in a developing country can be economically, intellectually and personally challenging, but funding and other opportunities may be broader than they may seem from afar. Selene Fernandez-Valverde recounts her challenges in starting a research group in Mexico.

Mentorship is an important component of academic success. Here, I share my personal experience as a mentee and a mentor from the perspective of a junior principal investigator. Vaishnavi Ananthanarayanan, who is a junior PI at the Indian Institute of Science in Bangalore, India, shares her personal experience as a mentee and a mentor.

A non-catalytic function of PRC1 is required for chromatin interactions that can facilitate developmental gene activation.

Premalignant skin stem cells become dependent on extracellular serine for proliferation, and this metabolic reprogramming inhibits tumour-suppressing cell differentiation.

The coronavirus disease-19 (COVID-19) pandemic underscores the threat posed by newly emerging viruses. Understanding the biology of novel viruses rests in large part on in vitro models that allow viral replication. Human and animal organoids are now proving their value as an experimental virology platform. Hans Clevers discusses the value of organoids as an experimental platform for understanding the

RNA tailing, or the addition of non-templated nucleotides to the 3′ end of RNA, is the most frequent and conserved type of RNA modification. The addition of tails and their composition reflect RNA maturation stages and have important roles in determining the fate of the modified RNAs. Apart from canonical poly(A) polymerases, which add poly(A) tails to mRNAs in a transcription-coupled manner, a family

Cellular stress induced by the abnormal accumulation of unfolded or misfolded proteins at the endoplasmic reticulum (ER) is emerging as a possible driver of human diseases, including cancer, diabetes, obesity and neurodegeneration. ER proteostasis surveillance is mediated by the unfolded protein response (UPR), a signal transduction pathway that senses the fidelity of protein folding in the ER lumen

The term ‘extracellular vesicles’ refers to a heterogeneous population of vesicular bodies of cellular origin that derive either from the endosomal compartment (exosomes) or as a result of shedding from the plasma membrane (microvesicles, oncosomes and apoptotic bodies). Extracellular vesicles carry a variety of cargo, including RNAs, proteins, lipids and DNA, which can be taken up by other cells,

The cGAS-STING signalling axis, comprising the synthase for the second messenger cyclic GMP-AMP (cGAS) and the cyclic GMP-AMP receptor stimulator of interferon genes (STING), detects pathogenic DNA to trigger an innate immune reaction involving a strong type I interferon response against microbial infections. Notably however, besides sensing microbial DNA, the DNA sensor cGAS can also be activated

Bass and colleagues uncover a role for NAD+ in preventing age-related decline in circadian function in mice.

Autophagosomes are double-membrane vesicles newly formed during autophagy to engulf a wide range of intracellular material and transport this autophagic cargo to lysosomes (or vacuoles in yeasts and plants) for subsequent degradation. Autophagosome biogenesis responds to a plethora of signals and involves unique and dynamic membrane processes. Autophagy is an important cellular mechanism allowing the

A group of endogenous 22-nucleotide siRNAs, which is produced by Dicer-like 2 proteins, represses translation and contributes to plant adaptation to environmental stress.

Many protein-coding genes in higher eukaryotes can produce circular RNAs (circRNAs) through back-splicing of exons. CircRNAs differ from mRNAs in their production, structure and turnover and thereby have unique cellular functions and potential biomedical applications. In this Review, I discuss recent progress in our understanding of the biogenesis of circRNAs and the regulation of their abundance and

Ilya Levental outlines maturation of the concept of lipid rafts as an organizational principle of biomembranes.

Coronaviruses employ various nuclear signalling mechanisms for their propagation. Here we link replication of coronaviruses, including SARS-CoV-2, the coronavirus disease 2019 (COVID-19)-causing virus, with cytoskeleton-dependent signalling and 3D genome organization. This link could provide novel insights into the high coronavirus pathogenicity in certain cellular states, particularly those associated

Parkinson disease is a devastating neurodegenerative condition that is characterized by intraneuronal toxic assemblies of the α-synuclein protein. In this Comment, we discuss the emerging role of lipids in understanding biology as well as in the identification of new therapeutic targets in this disease. Avraham Ashkenazi draws attention to the role of lipids in the pathology of Parkinson disease.

Mutations cause phenotypic changes by perturbing the organization of molecular networks and the functions that emerge from these networks. A model of a cell based on molecular interactions will be required in order to understand the molecular mechanisms underlying complex traits. Mutations perturb molecular networks; thus, a model of molecular interactions will be required to fully understand complex

In this Journal Club, Audrey Williams and Sally Horne-Badovinac highlight the importance of studying the basal cell surface and its dynamics to understand epithelial cell behaviours and tissue rearrangements.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Lluís Ribas de Pouplana outlines the unanswered questions of mitochondrial transcription.

Identifying factors bound to specific genomic loci in an unbiased manner is the holy grail of chromatin research, because it would provide an ultimate description of locus function. In this Comment, we explain why purifying a single locus represents a major technical challenge and provide recommendations for achieving this goal. Michiel Vermeulen and Jérôme Déjardin recommend how best to characterize

Xavier Trepat highlights the first approach to measurement of forces exerted by cells