A year in the molecular life sciences: 2024 highlights.

The FEBS Journal editorial team reviews the articles we published in 2024 and reflects on the year's highlights. The articles summarised here broadly cluster in three themes-molecular and cell biology across species, immunology, and cutting-edge methods-whilst still showcasing the diversity of the scientific fields the journal covers. We look forward to many more excellent articles in 2025 and hope these highlights will inspire you to submit your next manuscript to The FEBS Journal.

In conversation with Alexander Wlodawer.

Alexander Wlodawer is a structural biologist who has made seminal contributions to our understanding of protein structure-function relationships. He obtained his PhD from the University of California, Los Angeles, and has spent the majority of his career at the National Cancer Institute in Frederick, Maryland, where he currently holds a Senior Investigator position at the NCI's Center for Structural Biology. He has been a member of the Editorial Board of The FEBS Journal since 2007.

Rewarding excellence: the 2024 FEBS Journal Richard Perham prize.

This editorial highlights and celebrates the winner of the 2024 Richard Perham prize. This was selected from shortlisted original articles that were published in The FEBS Journal in 2023 and received prize nominations from the Editorial Board. The winning paper, by Matteo Brindisi, Luca Frattaruolo, Federica Sotgia, Michael P Lisanti, Anna Rita Cappello and colleagues, shows how high cholesterol levels promote breast cancer aggressiveness.

Synergistic modelling of human disease.

Living model systems, ranging in complexity from bacterial culture to non-human primates, are a cornerstone in disease biology research. Despite their unquestionable usefulness, the disease modelling community remains acutely aware of the challenges and limitations of any individual model. To describe our collective predicament, we often (mis)use the quote by statistician George Box, ‘All models are wrong, but some are useful’.

The importance of figures in scientific 'show and tell'.

At Disease Models & Mechanisms, we are prioritising and investing in high-quality scientific figures to ensure that the communication of disease biology is accessible and engaging to all.

Supporting the translation of multiscale research in rare disease.

In anticipation of our upcoming Special Issue, ‘Translating Multiscale Research in Rare Disease’, we celebrate the strides taken in rare disease research that are improving patient diagnosis, prognosis and treatment.

From mechanisms of heart failure to clinical heart success.

This Editorial introduces DMM's new Special Issue on ‘Moving heart failure to heart success’. The Guest Editors reflect on how articles in the issue advance the cardiac research field.

Collaboration and knowledge integration for successful brain therapeutics - lessons learned from the pandemic.

Brain diseases are a major cause of death and disability worldwide and contribute significantly to years of potential life lost. Although there have been considerable advances in biological mechanisms associated with brain disorders as well as drug discovery paradigms in recent years, these have not been sufficiently translated into effective treatments. This Special Article expands on Keystone Symposia's pre- and post-pandemic panel discussions on translational neuroscience research.

Sharing resources to advance translational research.

The publication of Resource articles is essential for the dissemination of novel, or substantially enhanced, tools, techniques, disease models, datasets and resources. By sharing knowledge and resources in a globally accessible manner, we can support human disease research to accelerate the translation of fundamental discoveries to effective treatments or diagnostics for diverse patient populations. To promote and encourage excellence in Resource articles, Disease Models & Mechanisms (DMM) is launching a new 'Outstanding Resource Paper Prize'.

Genetic variance in human disease - modelling the future of genomic medicine.

DMM is launching a new Subject Focus on genetic variance in human disease. Here, we discuss this ongoing series of invited articles and reflect on advances in understanding the genotype–phenotype complexities in disease.

Disease Models & Mechanisms helps move heart failure to heart success.

Heart failure affects ∼64 million people worldwide, resulting in high morbidity, mortality and societal cost. Current treatment strategies are primarily geared at slowing the progression to an advanced disease state, but do not reverse or cure heart failure. A more comprehensive understanding of the underlying biology and development of preclinical models of this heterogeneous group of disorders will improve diagnosis and treatment.

Understanding and drugging RAS: 40 years to break the tip of the iceberg.

Several cancers and rare genetic diseases are caused by dysregulation in the RAS signaling pathway. RAS proteins serve as molecular switches that regulate pathways involved in cellular growth, differentiation and survival. These pathways have been an intense area of investigation for four decades, since the initial identification of somatic RAS mutations linked to human cancers.

Novel patient-derived models of desmoplastic small round cell tumor confirm a targetable dependency on ERBB signaling.

Desmoplastic small round cell tumor (DSRCT) is characterized by the t(11;22)(p13;q12) translocation, which fuses the transcriptional regulatory domain of EWSR1 with the DNA-binding domain of WT1, resulting in the oncogenic EWSR1-WT1 fusion protein. The paucity of DSRCT disease models has hampered preclinical therapeutic studies on this aggressive cancer. Here, we developed preclinical disease models and mined DSRCT expression profiles to identify genetic vulnerabilities that could be leveraged for new therapies.

Therapeutic Potential of NTRK3 Inhibition in Desmoplastic Small Round Cell Tumor.

Purpose: Desmoplastic small round cell tumor (DSRCT) is a highly lethal intra-abdominal sarcoma of adolescents and young adults. DSRCT harbors a t(11;22)(p13:q12) that generates the EWSR1-WT1 chimeric transcription factor, the key oncogenic driver of DSRCT. EWSR1-WT1 rewires global gene expression networks and activates aberrant expression of targets that together mediate oncogenesis.

Travel grants and how to use them (when there's no travel).

This Editorial discusses how DMM and its publisher, The Company of Biologists, have adapted the financial support they provide to the biological community in these unprecedented times.

Moving neuromuscular disorders research forward: from novel models to clinical studies.

Neuromuscular disorders (NMDs) encompass a diverse group of genetic diseases characterized by loss of muscle functionality. Despite extensive efforts to develop therapies, no curative treatment exists for any of the NMDs. For multiple disorders, however, therapeutic strategies are currently being tested in clinical settings, and the first successful treatments have now entered clinical practice (e.

From blood development to disease: a paradigm for clinical translation.

Translating basic research to the clinic is a primary aim of Disease Models & Mechanisms, and the recent successes in hematopoiesis research provide a blueprint of how fundamental biological research can provide solutions to important clinical problems. These advances were the main motivation for choosing hematopoiesis disorders as the focus of our inaugural meeting, 'Blood Disorders: Models, Mechanisms and Therapies', which was held in early October 2019. This Editorial discusses the reasons for and the challenges of interdisciplinary research in hematopoiesis, provides examples of how research in model systems is a key translational step towards effective treatments for blood disorders and summarizes what the community believes are the key exciting developments and challenges in this field.

From gene to treatment: supporting rare disease translational research through model systems.

Individual rare diseases may affect only a few people, making them difficult to recognize, diagnose or treat by studying humans alone. Instead, model organisms help to validate genetic associations, understand functional pathways and develop therapeutic interventions for rare diseases. In this Editorial, we point to the key parameters in face, construct, predictive and target validity for accurate disease modelling, with special emphasis on rare disease models.

Integrative Molecular Characterization of Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) is a highly lethal cancer of the lining of the chest cavity. To expand our understanding of MPM, we conducted a comprehensive integrated genomic study, including the most detailed analysis of alterations to date. We identified histology-independent molecular prognostic subsets, and defined a novel genomic subtype with and mutations and extensive loss of heterozygosity.

Current and Future Management of Malignant Mesothelioma: A Consensus Report from the National Cancer Institute Thoracic Malignancy Steering Committee, International Association for the Study of Lung Cancer, and Mesothelioma Applied Research Foundation.

On March 28- 29, 2017, the National Cancer Institute (NCI) Thoracic Malignacy Steering Committee, International Association for the Study of Lung Cancer, and Mesothelioma Applied Research Foundation convened the NCI-International Association for the Study of Lung Cancer- Mesothelioma Applied Research Foundation Mesothelioma Clinical Trials Planning Meeting in Bethesda, Maryland. The goal of the meeting was to bring together lead academicians, clinicians, scientists, and the U.S.

Generation of conditional oncogenic chromosomal translocations using CRISPR-Cas9 genomic editing and homology-directed repair.

Chromosomal rearrangements encoding oncogenic fusion proteins are found in a wide variety of malignancies. The use of programmable nucleases to generate specific double-strand breaks in endogenous loci, followed by non-homologous end joining DNA repair, has allowed several of these translocations to be generated as constitutively expressed fusion genes within a cell population. Here, we describe a novel approach that combines CRISPR-Cas9 technology with homology-directed repair to engineer, capture, and modulate the expression of chromosomal translocation products in a human cell line.

Quaternary Ti-20Nb-10Zr-5Ta alloy during immersion in simulated physiological solutions: formation of layers, dissolution and biocompatibility.

Samples of the quaternary Ti-20Nb-10Zr-5Ta alloy were immersed in Hanks' simulated physiological solution and in minimum essential medium (MEM) for 25 days. Samples of Ti metal served as controls. During immersion, the concentration of ions dissolved in MEM was measured by inductively coupled plasma mass spectrometry, while at the end of the experiment the composition of the surface layers was analyzed by X-ray photoelectron spectroscopy, and their morphology by scanning electron microscopy equipped for chemical analysis.

Hyaluronic acid stimulates the formation of calcium phosphate on CoCrMo alloy in simulated physiological solution.

The behaviour of CoCrMo alloy has been studied in two simulated physiological solutions-NaCl and Hanks' solutions-each containing the sodium salt of hyaluronic acid. Hyaluronic acid is a component of synovial joint fluid, so the behaviour of orthopaedic alloys in its presence needs to be assessed. Electrochemical methods, X-ray photoelectron spectroscopy and scanning electron microscopy have been used to analyse the composition, thickness and morphology of any layers formed on the alloy.