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Literature reviews are valuable resources for the scientific community. With research accelerating at an unprecedented speed in recent years and more and more original papers being published, review articles have become increasingly important as a means to keep up to date with developments in a particular area of research. A good review article provides readers with an in-depth understanding of a field and highlights key gaps and challenges to address with future research. Writing a review article also helps to expand the writer's knowledge of their specialist area and to develop their analytical and communication skills, amongst other benefits. Thus, the importance of building review-writing into a scientific career cannot be overstated. In this instalment of The FEBS Journal's Words of Advice series, I provide detailed guidance on planning and writing an informative and engaging literature review.

Over the past few decades, epigenetic regulators have emerged as major players in cellular processes that drive cancer initiation and progression, and subsequently modulate the responsiveness of cancers to therapeutic agents. This Special Issue of The FEBS Journal, Cancer Epigenetics, features an exciting collection of review articles that focus on the functions of a broad spectrum of epigenetic modulators in cancer. The diverse topics explored herein range from the roles of transposable elements and chromatin architecture in cancer and the most recent research advances on cancer-associated histone variants (oncohistones), to the effects of altered epigenetics on transcription and advanced cancer cell phenotypes. Moreover, the prospective key function of cancer metabolism in linking epigenetics and transcriptional regulation, and the potential of epigenetics for targeted cancer therapeutics is discussed. We hope that this collection of articles will give readers an enlightening overview of the most recent advances in the fast-moving field of cancer epigenetics.

When the novel coronavirus was described in late 2019, it could not have been imagined that within a year, more than 100 vaccine candidates would be in preclinical development and several would be in clinical trials and even approved for use. The scale of the COVID‐19 outbreak pushed the scientific community, working in collaboration with pharmaceutical companies, public health bodies, policymakers, funders and governments, to develop vaccines against SARS‐CoV‐2 at record‐breaking speed. As well as driving major amendments to the usual timeframe for bringing a vaccine to fruition, the pandemic has accelerated the development of next‐generation technologies for vaccinology, giving rise to two frontrunner RNA vaccines. Although none of the critical safety and efficacy steps have been skipped within the compressed schedules, and the technologies underpinning the novel vaccines have been refined by scientists over many years, a significant proportion of the global population is sceptical of the benefits of COVID‐19 vaccines and wary of potential risks. In this interview‐based article, we give an overview of how the vaccines were developed and how they work to generate a robust immune response against COVID‐19, as well as addressing common questions relating to safety and efficacy., The COVID‐19 outbreak has had a huge global impact, prompting the scientific community to develop a range of vaccines against the disease at an accelerated pace. Public reactions to the unprecedentedly rapid development and delivery of COVID‐19 vaccines have been mixed, with a significant minority expressing concerns about vaccine safety and efficacy. In particular, vaccines utilising relatively new mRNA‐based technology have come under intense scrutiny. Here, renowned immunologists Daniel Altmann and Victoria Male aim to clarify the science and alleviate concern by addressing several key questions relating to the development, mechanisms and effects of the vaccines.

Christine J. Watson is Professor of Cell and Cancer Biology at the University of Cambridge. Christine obtained her Bachelor's (honors) degree in Biochemistry at the University of Glasgow in 1975 and, after a soujourn in Glauco Tocchini-Valentini's lab at the Institute of Cell Biology, Consiglio Nazionale delle Ricerche in Rome, she undertook a PhD in Molecular Genetics at Imperial College London. During her PhD, she looked at differences in gene expression between differentiated and undifferentiated embryonal carcinoma stem cells, inspiring an early interest in gene expression and cell fate determination. Between 1986 and 1992, Christine undertook three postdoctoral research positions that took her from London back to Scotland, where she was first introduced to mammary gland biology through her work with John Clark at the Roslin Institute in Edinburgh. During her time in the Clark lab, Christine identified a factor - later shown to be STAT5 - that binds to the promoter of the milk protein gene β-lactoglobulin. This prompted further work identifying the key role played by the STAT family of transcription factors in mammary gland development. Shortly afterwards, Christine became a group leader at the Roslin Institute and later relocated to the University of Edinburgh to collaborate with Andrew Wyllie. This led to her recruitment to the University of Cambridge in 1998, where she has remained to date. Over the last two decades, the Watson lab has focused on elucidating the mechanisms underlying lineage commitment of mammary stem and progenitor cells and the regulation of cell death in involuting mammary gland. In this interview, Christine discusses her research highlights and provides a glimpse into her personal interests, as she moves towards retirement.

Nigel Scrutton FRS is Professor of Molecular Enzymology and Biophysical Chemistry at the University of Manchester and former Director of the Manchester Institute of Biotechnology (MIB). He obtained a first‐class degree in Biochemistry from King’s College London and followed this with a PhD at the University of Cambridge. His doctoral research, undertaken in Richard Perham’s laboratory, yielded fundamental breakthroughs in enzyme redesign that have stood the test of time. Nigel was awarded a ScD degree by the University of Cambridge in 2003. After faculty positions at the University of Leicester, Nigel was appointed Professor at the University of Manchester in 2005. Over the last 15 years, he has cemented his reputation as a world leader in the fields of enzyme engineering and biocatalysis, synthetic biology, biophysics and biomanufacturing, notably by establishing and directing the Synthetic Biology Research Centre ‘SYNBIOCHEM’ and UK Future Biomanufacturing Research Hub. In recognition of his scientific contributions, he has received many academic awards and accolades, including being elected as Fellow of the Royal Society earlier this year. In this interview, he highlights how fundamental studies of enzymatic catalysis and mechanisms are driving key advances in biotechnology and biomanufacturing, and describes how the experiences and mentors of his formative years helped to shape his successful career at the interface between discovery and application‐focused science.

Professor Dame Janet Thornton is a pioneer in structural bioinformatics who has developed an extensive computational toolkit for the analysis of protein structure and inference of function and evolution. She began her career in science as a physicist, following an undergraduate degree in physics from the University of Nottingham with a Master's and PhD in biophysics in London. After undertaking a postdoctoral position in the group of Sir David Phillips at the University of Oxford, Janet returned to London where she eventually held professorial appointments at both University College London and Birkbeck College. During this period, she formed a number of long-standing and fruitful collaborations that, amongst other advances, led to the development of a software that revolutionised protein structure validation - PROCHECK - as well as a unique classification system for protein structures, CATH. Janet was Director of the European Bioinformatics Institute EMBL-EBI between 2001 until 2015 and played a pivotal role in launching ELIXIR, a pan-European infrastructure for biological data. She remains at EMBL-EBI as a senior scientist, and her group primarily focuses on understanding protein structure and function and how these contribute to our understanding of diseases and ageing. Her contributions to the life sciences have been distinguished through numerous awards and honours, and in 2012, she was appointed a Dame Commander of the Order of the British Empire for services to bioinformatics.

Type III Secretion Systems (T3SS) deliver subunits from the bacterial cytosol to nascent cell surface flagella. Early flagellar subunits that form the rod and hook substructures are unchaperoned and contain their own export signals. A gate recognition motif (GRM) docks them at the FlhBc component of the FlhAB-FliPQR export gate, but the gate must then be opened and subunits must be unfolded to pass through the flagellar channel. This induced us to seek further signals on the subunits. Here, we identify a second signal at the extreme N-terminus of flagellar rod and hook subunits and determine that key to the signal is its hydrophobicity. We show that the two export signal elements are recognised separately and sequentially, as the N-terminal signal is recognised by the flagellar export machinery only after subunits have docked at FlhBC via the GRM. The position of the N-terminal hydrophobic signal in the subunit sequence relative to the GRM appeared to be important, as a FlgD deletion variant (FlgDshort), in which the distance between the N-terminal signal and the GRM was shortened, 'stalled' at the export machinery and was not exported. The attenuation of motility caused by FlgDshort was suppressed by mutations that destabilised the closed conformation of the FlhAB-FliPQR export gate, suggesting that the hydrophobic N-terminal signal might trigger opening of the flagellar export gate., University of Cambridge John Lucas Walker studentship

The FEBS Journal announces the winners and runners-up of its COVID-19 Creative Communication Competition in which entrants were asked to depict 'post-lockdown lab life'.

Gerard Evan is Head of Department and Sir William Dunn Professor at the Department of Biochemistry, University of Cambridge, UK. Driven by his innate passion to understand how things work, Gerard has devoted much of his career to understanding the molecular basis of cancer, particularly the roles played by oncogenes such as Myc. His work has helped elucidate the complex role that this gene plays in cell proliferation and apoptosis, and paved new avenues for the treatment of aggressive cancers. In this interview, Gerard provides an overview of what is known about the role of Myc in normal and cancer cells and provides a persuasive argument for the application of 'impersonalised therapy' involving Myc inhibition as part of future chemotherapeutic drug regimes.

Sarah Teichmann is Head of Cellular Genetics at the Wellcome Sanger Institute and visiting research group leader at the European Bioinformatics Institute (EMBL-EBI). Sarah was appointed to the Sanger Institute and EMBL-EBI in 2013; prior to this she was a research group leader at the MRC Laboratory of Molecular Biology (LMB), where she first set up her group in 2001. The Teichmann lab is interested in global principles of protein interactions and gene expression, and in recent years has exploited cutting-edge single-cell genomics technologies to explore key questions relating to immune system function. In 2016, she co-founded the Human Cell Atlas initiative to map every cell type in the human body using single-cell transcriptomic technologies and spatial methods. Sarah has received many prestigious awards in recognition of her contributions to understanding protein complex assembly and gene regulatory networks. In this interview, she relays the story behind some of her research breakthroughs, discusses her career path and most influential mentors, and tells us why looking at biology at the level of a single cell can be so powerful and illuminating.

Peer review, the system by which manuscripts submitted for publication are evaluated by experts (peers) in a field, is the cornerstone of high-quality scholarly publishing. By commenting on the originality, significance and completeness of submitted manuscripts, peer reviewers improve the standard of published work and play a key part in preventing flawed research from being widely distributed. This Words of Advice article highlights the importance of developing the skill of reviewing papers from early on in a scientific career and provides tips on navigating all stages of the process, as well as flagging some common mistakes.

Type III Secretion Systems (T3SS) deliver subunits from the bacterial cytosol to nascent cell surface flagella. Early flagellar subunits that form the rod and hook substructures are unchaperoned and contain their own export signals. A gate recognition motif (GRM) docks them at the FlhBc component of the FlhAB-FliPQR export gate, but the gate must then be opened and subunits must be unfolded to pass through the flagellar channel. This induced us to seek further signals on the subunits. Here, we identify a second signal at the extreme N-terminus of flagellar rod and hook subunits and determine that key to the signal is its hydrophobicity. We show that the two export signal elements are recognised separately and sequentially, as the N-terminal signal is recognised by the flagellar export machinery only after subunits have docked at FlhBCvia the GRM. The position of the N-terminal hydrophobic signal in the subunit sequence relative to the GRM appeared to be important, as a FlgD deletion variant (FlgDshort), in which the distance between the N-terminal signal and the GRM was shortened, ‘stalled’ at the export machinery and was not exported. The attenuation of motility caused by FlgDshort was suppressed by mutations that destabilised the closed conformation of the FlhAB-FliPQR export gate, suggesting that the hydrophobic N-terminal signal might trigger opening of the flagellar export gate.

Sir Gregory Winter, Research Leader Emeritus at the MRC Laboratory of Molecular Biology (LMB) in Cambridge, UK is best known for his pioneering work on humanised and human therapeutic antibodies. Greg's research career has been entirely based in Cambridge. After studying Natural Sciences at Cambridge University, he undertook his PhD, focused on determining the amino acid sequence of bacterial tryptophanyl tRNA synthetase, at the LMB, where he remained for postdoctoral research and the ensuing establishment of his own research group. His long-standing interest in protein and nucleic acid sequencing led to the development of techniques to 'humanise' mouse monoclonal antibodies and to make human antibodies directly, resulting in promising antibody-based therapies for cancer and autoimmune diseases. Greg has founded three biotech companies, including Cambridge Antibody Technology and Bicycle Therapeutics. He has also received numerous awards and honours in recognition of his revolutionary work in the antibody engineering field, most notably the Nobel Prize in Chemistry in October 2018. One year on, he discusses the impact of this award on his life and future career outlook in an interview with The FEBS Journal.

Neurodegeneration is a feature of many debilitating, incurable diseases that are rapidly rising in prevalence, such as Parkinson's disease. There is an urgent need to develop new and more effective therapeutic strategies to combat these devastating diseases. Models – from cell-based systems, to unicellular organisms, to complex animals – have proven to be a useful tool to help the research community shed light on the mechanisms underlying neurodegenerative diseases, and these advances have now begun to provide promising therapeutic avenues. In this themed issue of Disease Models & Mechanisms, a special collection of articles focused on neurodegenerative diseases is introduced. The collection includes original research articles that provide new insights into the complex pathophysiology of such diseases, revealing candidate biomarkers or therapeutic targets. Some of the articles describe a new disease model that enables deeper exploration of key mechanisms. We also present a series of reviews that highlight some of the recent translational advances made in studies of neurodegenerative diseases. In this Editorial, we summarize the articles featured in this collection, emphasizing the impact that model-based studies have made in this exciting area of research., Summary: This Editorial introduces a new Special Collection, ‘Neurodegeneration: from models to mechanisms to therapies’, providing a summary of the research and review articles published in this launch issue, as well as highlighting some of DMM's most-read neurodegeneration-related articles from recent issues.

Gerald (Gerry) Rubin, pioneer in Drosophila genetics, is Founding Director of the HHMI-funded Janelia Research Campus. In this interview, Gerry recounts key events and collaborations that have shaped his unique approach to scientific exploration, decision-making, management and mentorship – an approach that forms the cornerstone of the model adopted at Janelia to tackle problems in interdisciplinary biomedical research. Gerry describes his remarkable journey from newcomer to internationally renowned leader in the fly field, highlighting his contributions to the tools and resources that have helped establish Drosophila as an important model in translational research. Describing himself as a ‘tool builder’, his current focus is on developing approaches for in-depth study of the fly nervous system, in order to understand key principles in neurobiology. Gerry was interviewed by Ross Cagan, Senior Editor of Disease Models & Mechanisms., Drosophila Collection: Ross Cagan spoke to Gerry Rubin about his career path and the story behind some of his key breakthroughs, as well as his unique and successful approach to management and mentorship.

Drosophila melanogaster has been adopted as one of the most-used model systems since it was first introduced by Thomas Morgan for the study of heredity in the early 20th century. Its experimental tractability and similarity of its biological pathways to those of humans have placed the model at the forefront of research into human development and disease. With the ongoing accumulation of genetic tools and assays, the fly community has at its fingertips the resources to generate diverse Drosophila disease models for the study of genes and pathways involved in a wide range of disorders. In recent years, the fly has also been used successfully for drug screening. In this Editorial, we introduce a Special Collection of reviews, interviews and original research articles that highlight some of the many ways that Drosophila has made, and continues to make, an impact on basic biological insights and translational science., Drosophila Collection: This Editorial introduces a new Special Collection, ‘Spotlight on Drosophila: Translational Impact’, providing a summary of its contents so far and highlighting the impact of Drosophila as a model for human diseases.

Experiments that use the mouse as a model for disease have recently come under scrutiny because of the repeated failure of data, particularly derived from preclinical studies, to be replicated or translated to humans. The usefulness of mouse models has been questioned because of irreproducibility and poor recapitulation of human conditions. Newer studies, however, point to bias in reporting results and improper data analysis as key factors that limit reproducibility and validity of preclinical mouse research. Inaccurate and incomplete descriptions of experimental conditions also contribute. Here, we provide guidance on best practice in mouse experimentation, focusing on appropriate selection and validation of the model, sources of variation and their influence on phenotypic outcomes, minimum requirements for control sets, and the importance of rigorous statistics. Our goal is to raise the standards in mouse disease modeling to enhance reproducibility, reliability and clinical translation of findings., Summary: Raising standards for carrying out and reporting mouse model studies will improve reproducibility and relevance to human disease research.

Owen Sansom, Deputy Director of the Cancer Research UK Beatson Institute, began his research career investigating the molecular mechanisms of apoptosis. Over the course of his work he has moved progressively into a more translational arena, and the current focus of his lab is to understand the signalling pathways underlying colorectal and pancreatic cancers. The Sansom lab uses mouse models to pinpoint how mutations that commonly occur in these frequently deadly cancers co-operate to promote tumorigenesis in vivo. This work has provided many important insights into the molecular changes associated with intestinal and pancreatic neoplasia and has revealed new targets for drug development. Here, Owen tells the stories behind some of his most exciting breakthroughs, describes the experiences and mentors that shaped his research interests and style of running a lab, and discusses the challenges of recapitulating the complexity of cancer as well as translating preclinical evidence to patient therapies.

The Bohmann lab, based at the University of Rochester Medical Center in New York, uses Drosophila to explore the cross-talk between stress and metabolic regulation, with the goal of understanding how the signaling pathways involved can drive aging, cancer and other degenerative pathologies. In this interview, Dirk Bohmann describes his motives for moving into the fly field, explains how the study of aging can give important insights into complex disease mechanisms, and advocates using a systems-biology approach to advance drug discovery.

Future prospects continue to be strong for research using the rat as a model organism. New technology has enabled the proliferation of many new transgenic and knockout rat strains, the genomes of more than 40 rat strains have been sequenced, publications using the rat as a model continue to be produced at a steady rate, and discoveries of disease-associated genes and mechanisms from rat experiments abound, frequently with conservation of function between rats and humans. However, advances in genome technology have led to increasing insights into human disease directly from human genetic studies, pulling more and more researchers into the human genetics arena and placing funding for model organisms and their databases under threat. This, therefore, is a pivotal time for rat-based biomedical research – a timely moment to review progress and prospects – providing the inspiration for a new Special Collection focused on the impact of the model on translational science, launched in this issue of Disease Models & Mechanisms. What disease areas are most appropriate for research using rats? Why should the rat be favoured over other model organisms, and should the present levels of funding be continued? Which approaches should we expect to yield biologically and medically useful insights in the coming years? These are key issues that are addressed in the original Research Articles and reviews published in this Special Collection, and in this introductory Editorial. These exemplar articles serve as a landmark for the present status quo after a decade of major advances using the rat model and could help to guide the direction of rat research in the coming decade., Summary: This Editorial introduces a new Special Collection, ‘Spotlight on Rat: Translational Impact’, providing a summary of the articles published in this launch issue and a flavour of what's to come, as well as highlighting the impact rat models have made and continue to make on understanding human disease.

The bacterial flagellum assembles in a strict order, with structural subunits delivered to the growing flagellum by a type III export pathway. Early rod-and-hook subunits are exported before completion of the hook, at which point a subunit-specificity switch allows export of late filament subunits. This implies that in bacteria with multiple flagella at different stages of assembly, each export pathway can discriminate and sort unchaperoned early and chaperoned late subunits. To establish whether subunit sorting is distinct from subunit transition from the cytosol to the membrane, in particular docking at the membrane-associated FliI ATPase, the pathway was manipulated in vivo. When ATP hydrolysis by the FliI ATPase was disabled and when the pathway was locked into an early export state, both unchaperoned early and chaperoned late subunits stalled and accumulated at the inner membrane. Furthermore, a chaperone that attenuates late subunit export by stalling when docked at the wild-type ATPase also stalled at the ATPase in an early-locked pathway and inhibited export of early subunits in both native and early-locked pathways. These data indicate that the pathways for early and late subunits converge at the FliI ATPase, independent of ATP hydrolysis, before a distinct, separable sorting step. To ascertain the likely signals for sorting, the export of recombinant subunits was assayed. Late filament subunits unable to bind their chaperones were still sorted accurately, but chaperoned late subunits were directed through an early-locked pathway when fused to early subunit N-terminal export signal regions. Furthermore, while an early subunit signal directed export of a heterologous type III export substrate through both native and early-locked pathways, a late subunit signal only directed export via native pathways. These data suggest that subunits are distinguished not by late chaperones but by N-terminal export signals of the subunits themselves.

In recent years, the zebrafish has emerged as an increasingly prominent model in biomedical research. To showcase the translational impact of the model across multiple disease areas, Disease Models & Mechanisms has compiled a Special Issue that includes thought-provoking reviews, original research reporting new and important insights into disease mechanisms, and novel resources that expand the zebrafish toolkit. This Editorial provides a summary of the issue’s contents, highlighting the diversity of zebrafish disease models and their clinical applications. Special Issue: Spotlight on Zebrafish One aim of a Disease Models & Mechanisms (DMM) ‘Special Issue’ is to highlight how emerging disease models can lead to exceptional growth in particular areas of translational research. This is especially true for this issue, Spotlight on Zebrafish: Translational Impact. The zebrafish has traditionally been used to study developmental biology. Its optical transparency for the first few weeks, high fecundity and ex vivo fertilization have meant that the fundamental processes and mechanisms of vertebrate embryo development from a single cell through to a swimming fish can be studied in exquisite detail. Over the past decade these same features have enabled the zebrafish to become a preeminent disease model and tool for studying disease mechanisms. Importantly, discoveries EDITORIAL

DNA replication and transcription are essential processes for cell growth and division. The polymerase complexes charged with these tasks share the same template and so there is a potential for conflict between the two. Studies both in vivo and in vitro indicate that RNA polymerase complexes can indeed arrest the progress of replication forks and that cell viability is endangered as a result. Stable ternary complexes formed at lesions in the template DNA or as a result of backtracking may be especially troublesome. Numerous processes have evolved to reduce conflict between replication and transcription and to rescue any replication forks that suffer damage when conflict does occur. In bacteria, these systems are so highly tuned and co-ordinated that cells normally suffer few problems even under conditions allowing rapid growth and therefore demanding both efficient chromosome duplication and high levels of gene expression. The threat to genome transmission and cell viability becomes apparent when this interplay is disrupted.