Issues
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Cover image
Cover Image
Cover: The image shows neuronal cells differentiated from human induced pluripotent stem cells (iPSCs) as a model system for amyotrophic lateral sclerosis (ALS). ALS-associated mutations, such as the P525L shown here, cause cytoplasmic delocalisation of the nuclear protein FUS. Spinal cord derivatives, including motoneurons, were stressed by heat shock, which causes coalescence of delocalised FUS into stress granules. In this image, yellow speckles represent the overlay of FUS (red fluorescence) with the stress granule marker TIAR (green fluorescence). DAPI (blue fluorescence) is used as a nuclear counterstain. See article by Lenzi et al. on page 755.
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IN THIS ISSUE
A MODEL FOR LIFE
Unravelling proteinopathies: an interview with David Rubinsztein
David Rubinsztein is currently professor of Molecular Neurogenetics at the University of Cambridge, UK and Wellcome Trust Principal Research Fellow. He is based in the Cambridge Institute for Medical Research, where he is currently the Deputy Director. He started his studies in medicine in Cape Town, South Africa, and was initially interested in both clinical and research work. During his PhD, he discovered himself truly passionate about cell biology and genetics of disease and moved to Cambridge, where he specialised in Genetic Pathology, after which he received a 6-year Glaxo-Wellcome Fellowship to investigate mechanisms of protein misfolding and aggregation in Huntington's disease and other proteinopathies. Since then, he has been committed to lab research and has been a leading scientist in elucidating the roles of autophagy in neurodegeneration. In his lab, he combines cell biology tools with animal studies to elucidate the potential of autophagy manipulation as a strategy to eliminate toxic misfolded and aggregated proteins and treat neurodegenerative diseases. He has been recently appointed as academic lead PI for the Alzheimer's Research UK Drug Discovery Institute in Cambridge, whose goal is to develop disease-modifying treatments for neurodegenerative diseases. In this interview, David tells us how he developed his career as an independent scientist, sharing his experience and views about the scientific progress in our understanding of neurodegenerative diseases and in developing potential therapeutics.
REVIEW
Challenges in understanding psychiatric disorders and developing therapeutics: a role for zebrafish
Summary: In this review, we discuss strengths and limitations of prevalent laboratory models that are used for understanding psychiatric disorders and developing therapeutics, with emphasis on the zebrafish.
RESEARCH ARTICLES
Iron is a specific cofactor for distinct oxidation- and aggregation-dependent Aβ toxicity mechanisms in a Drosophila model
Highlighted Article: Iron plays a specific role in amyloid beta peptide (Aβ) toxicity in a Drosophila model system. Aβ and iron exhibit distinct toxicity mechanisms in oxidising and non-oxidising environments.
A Drosophila model to investigate the neurotoxic side effects of radiation exposure
Highlighted Article: To model delayed neurological deficits resulting from pediatric cranial radiation therapy, neurotoxic damage in adult Drosophila is assessed following larval irradiation with the goal of elucidating underlying pathological mechanisms.
Increased autophagy and apoptosis contribute to muscle atrophy in a myotonic dystrophy type 1 Drosophila model
Summary: Increased apoptosis and autophagy are processes that lead to muscle mass wasting in DM1, which is one of the most debilitating symptoms of the disease.
Cx3cr1 deficiency in mice attenuates hepatic granuloma formation during acute schistosomiasis by enhancing the M2-type polarization of macrophages
Highlighted Article: A reduction in CX3CR1 signaling provides protection for mice against pro-inflammatory responses and hepatic granuloma formation during acute schistosomiasis.
A mitochondrial therapeutic reverses visual decline in mouse models of diabetes
Summary: Visual decline in mouse models of diabetes is reversed, independently of treating other disease symptoms, by treatment with MTP-131, a water-soluble peptide that selectively targets cardiolipin and improves mitochondrial bioenergetics.
A new cellular model to follow Friedreich's ataxia development in a time-resolved way
Summary: This paper describes the development of a new cellular model to study the neurodegenerative Friedreich's ataxia based on the use and development of new CRISPR and TALEN platforms.
Chronic administration of recombinant IL-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in IL-6-deficient mice
Summary: The administration of rIL-6 might contribute to the aggravation of fatty liver disease through increasing lipogenesis in HFD-induced obesity.
IKKα is involved in kidney recovery and regeneration of acute ischemia/reperfusion injury in mice through IL10-producing regulatory T cells
Summary: IKKα in the kidney recovery and regeneration via regulatory T cells secreting IL10.
Molecular characterization of hepatocarcinogenesis using mouse models
Summary: We present initial data from systematic and longitudinal analyses of hepatocarcinogenesis using mouse models that reflect the human disease. This provides a rich resource for the analysis of biomarkers and sequential molecular alterations during disease progression.
RESOURCE ARTICLE
ALS mutant FUS proteins are recruited into stress granules in induced pluripotent stem cell-derived motoneurons
Summary: Mutated FUS protein is aberrantly delocalized and recruited into stress granules in iPSC-derived motoneurons, which provide a new model system for amyotrophic lateral sclerosis.
Call for papers: Moving Heart Failure to Heart Success

Disease Models & Mechanisms is pleased to welcome submissions for consideration for an upcoming special issue, Moving Heart Failure to Heart Success: Mechanisms, Regeneration & Therapy. The deadline for submitting articles to the special issue has been extended to 1 August 2022.
Modelling interactions at the blood–brain barrier

In their Review, Yvonne Adams and Anja Ramstedt Jensen review the available in vitro models to investigate the impact of adhesion of Plasmodium falciparum-infected red blood cells on the blood–brain barrier, a process associated with cerebral malaria.
Call for new preLighters

preLights is the preprint highlighting community supported by The Company of Biologists. At the heart of preLights are our preLighters: early-career researchers who select and write about interesting new preprints for the research community. We are currently looking for new preLighters to join our team. Find out more and apply here.
Focus on Genetic Variance in Human Disease

New technologies, computational methods and model systems are revealing how human genetic variance contributes to disease mechanisms. DMM’s new Subject Focus highlights this evolving area of research.
Apply for a DMM Conference Travel Grant

Aimed at early-career researchers wanting to attend in-person and virtual meetings, the next application deadline for a DMM Conference Travel Grant is 1 September 2022. Find out more and hear from past recipients about their experience of the grant.