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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.

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.

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.

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.

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.

Highlighted Article: A reduction in CX3CR1 signaling provides protection for mice against pro-inflammatory responses and hepatic granuloma formation during acute schistosomiasis.

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.

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.

Summary: The administration of rIL-6 might contribute to the aggravation of fatty liver disease through increasing lipogenesis in HFD-induced obesity.

Summary: IKKα in the kidney recovery and regeneration via regulatory T cells secreting IL10.

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.

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.