In conversation with Lori Passmore.

Lori Passmore is a Group Leader at the MRC Laboratory of Molecular Biology (MRC-LMB). She studied Biochemistry at the University of British Columbia in Vancouver (Canada), before moving to the UK in 1999 for a PhD at the Institute of Cancer Research. After completing her PhD, Lori moved to Cambridge, where she became a Post-Doctoral Fellow at the MRC-LMB. In 2009, Lori started her own group at the MRC-LMB and was subsequently awarded an ERC Starting Grant (2011), an ERC Consolidator Grant (2017) and a Wellcome Discovery Award (2023). She was also elected into the EMBO Young Investigator Programme (2015) and EMBO Membership (2018). Lori's research focusses on the determination of the structures of protein complexes that regulate gene expression, using primarily cryo-electron microscopy and in vitro assays. Her work has contributed significantly to our understanding of the underlying molecular mechanisms of cellular processes, giving insights into human physiology and disease. In this interview, Lori provides an overview of her research and discusses current challenges in the field, recalls the key events and collaborations that have helped shape her successful research career and offers advice to early career scientists.

In conversation with Carol Robinson.

Dame Carol Robinson is a professor of chemistry and Director of the Kavli Institute for Nanoscience Discovery at the University of Oxford. Carol's career in science began at the age of 16 as a lab technician at Pfizer (based in Kent), during which time she studied part-time and took evening classes to obtain a degree in chemistry. This was followed by a master's degree at the University of Swansea and a PhD at the University of Cambridge. Carol's postdoctoral training was undertaken in Peter Bennett's lab at the Department of Pathology and Microbiology, University of Bristol. Subsequently, she took a career break of 8 years to spend time with her family but made a strong comeback, taking up a position at the University of Oxford, where she began to explore protein folding. It was here that she first demonstrated, using the GroEL chaperonin-substrate complex as a prototype, that protein secondary structure can be analysed in the gas phase. Carol later made history as the first female professor of chemistry at the University of Cambridge (2001) and again as the first female professor of chemistry at the University of Oxford (2009). In her research, she has also continuously pushed boundaries, pioneering the application of mass spectrometry for the elucidation of the 3D architecture of macromolecular complexes, including membrane-bound assemblies. She has received many awards and honours in recognition of her significant contributions to the field of gas-phase structural biology, including the Royal Society Fellowship, the Davy Medal, the Rosalind Franklin Award and the FEBS/EMBO Women in Science Award. In this interview, she discusses some of her career highlights and ongoing research aspirations and draws on her unique experiences to offer advice to early career scientists.

In Conversation with John Cryan.

John F. Cryan is Chair of the Department of Anatomy and Neuroscience, Principal Investigator in the APC Microbiome Ireland Institute and Vice President for Research and Innovation at University College of Cork, Ireland. He obtained his bachelor's and doctoral degrees (in Biochemistry and Pharmacology, respectively) from the University of Galway and undertook postdoctoral research experience in the USA, at the University of Pennsylvania and The Scripps Research Institute. He was also a visiting fellow at the Department of Psychiatry, University of Melbourne, for a couple of years post-PhD. In 2002, John took up a position in industry as a laboratory head at the Novartis Institutes for BioMedical Research in Basel, Switzerland. After a 4-year stint at Novartis, he returned to academia in late 2005 as a Lecturer and then Senior Lecturer in Pharmacology at University College Cork (UCC). The Cryan lab now focuses on determining the impact of the gut microbiota on the human brain and behaviour, with a particular interest in the brain-gut-microbiome axis in the context of depression. John has published more than 600 peer-reviewed papers and has received many honours and accolades in recognition of his contributions to neuropharmacology and microbiome research, including the Datta lecture award from FEBS in 2022. In this interview, he outlines how he became interested in the role of the microbiome in brain development and disease, provides advice to budding scientists and highlights the broader public health implications of his research.

How to write a good scientific review article.

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.

Recognition of discrete export signals in early flagellar subunits during bacterial type III secretion.

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.

Cancer epigenetics: promises and pitfalls for cancer therapy.

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.

In conversation with Christine Watson.

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 ß-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.

COVID-19 vaccines: what do we know so far?

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.

How to be a good peer reviewer of scientific manuscripts.

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.

In conversation with Nigel Scrutton.

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 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.

In conversation with Janet Thornton.

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.

COVID-19 breakthroughs: separating fact from fiction.

The newly recognised coronavirus SARS-CoV-2, causative agent of coronavirus disease (COVID-19), has caused a pandemic with huge ramifications for human interactions around the globe. As expected, research efforts to understand the virus and curtail the disease are moving at a frantic pace alongside the spread of rumours, speculations and falsehoods. In this article, we aim to clarify the current scientific view behind several claims or controversies related to COVID-19. Starting with the origin of the virus, we then discuss the effect of ibuprofen and nicotine on the severity of the disease. We highlight the knowledge on fomites and SARS-CoV-2 and discuss the evidence and explications for a disproportionately stronger impact of COVID-19 on ethnic minorities, including a potential protective role for vitamin D. We further review what is known about the effects of SARS-CoV-2 infection in children, including their role in transmission of the disease, and conclude with the science on different mortality rates between different countries and whether this hints at the existence of more pathogenic cohorts of SARS-CoV-2.

Announcing the winners of our COVID-19 Creative Communication Competition.

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'.

In conversation with Gerard Evan.

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.

In conversation with Greg Winter.

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.

In conversation with Sarah Teichmann.

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.

Neurodegenerative disease: models, mechanisms, and a new hope.

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.

A RATional choice for translational research?

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.

Building genetic tools in Drosophila research: an interview with Gerald Rubin.

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.

Fruit flies on the front line: the translational impact of Drosophila.

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.