Aminoglycoside antibiotics can damage the hair cells of the inner ear, leading to hearing loss and balance disorders. Improved treatment paradigms have reduced the risk of adverse effects associated with these antibiotics, but permanent inner ear damage is still common. Hair cells are susceptible to damage because of their tendency to take up and retain aminoglycosides, whereas less vulnerable cells do not accrue aminoglycosides after exposure. To better understand the mechanisms that contribute to aminoglycoside toxicity, David Raible’s lab at the University of Washington imaged fluorescently-labeled aminoglycosides in the hair cells of live zebrafish. They found that the degree of aminoglycoside-induced toxicity was linked to how rapidly the antibiotic was distributed into lysosomes, suggesting that monitoring the kinetics of lysosomal delivery may be an effective way to evaluate different aminoglycoside treatment paradigms.
In the accompanying video, a time-lapse of zebrafish hair cells (green) shows the transit of fluorescently-labeled aminoglycosides (red) from the intracellular space into lysosomes. At the beginning of the video, aminoglycosides are visible as a diffuse pool in the cytosol. Within 20 minutes, the diffuse signal decreases as aminoglycosides merge into puncta, indicating their uptake into lysosomes.
Though Bruce Alberts is well known for his work on the biochemistry of DNA replication and as the editor-in-chief of Science, he is also recognizable as the author of the seminal biology textbook Molecular Biology of the Cell. Alberts served as the president of the National Academy of Sciences for over a decade and is currently a professor at University of California, San Francisco. This year, his dedication to advancing science policy and education was recognized with the Lasker-Koshland Special Achievement Award. JCI’s editor-at-large Ushma Neill sat down with Alberts to talk about how his background in science shaped his later work as an educator and leader in science policy. They also discuss the challenges of improving science education through writing, editing, and policy making.
Retinitis pigmentosa (RP) is a heterogeneous genetic disorder that is characterized by a progressive loss of photoreceptors that results in deterioration of vision. While gene therapy has shown promise for some forms of RP, over 60 genes have been implicated in this disorder; therefore, non-gene-targeted therapies are of great interest. In this episode, Stephen Tsang and colleagues discuss their study, which shows that upregulation of glycolytic flux, via targeted downregulation of sirtuin 6, in rod photoreceptors improves photoreceptor survival and preserves vision in a mouse model of RP. As this strategy is not gene-specific, it may be beneficial for a range of neurodegenerative disorders.
Cancer cells have a different response to nutrient limitation than healthy cells; therefore, targeting nutrient acquisition pathways has potential as a therapeutic strategy for limiting cancer cell growth. In this episode, Aimee Edinger discusses a recent study from her group, which describes the effects of a sphingolipid-based compound, SH-BC-893, in multiple pre-clinical cancer models. SH-BC-893 simultaneously disrupts both glucose and amino acid transporters and was effective against both rapid- and slow-growing tumors without affecting normal tissues. The results of this study support further exploration of the therapeutic potential of this compound.