David C. Rubinsztein
Showed that rapamycin induces autophagy to clear the toxic protein of Huntington's disease, and that where lysosomes sit inside a cell helps set mTORC1 activity
Professor of Molecular Neurogenetics, Department of Medical Genetics, University of Cambridge · Deputy Director, Cambridge Institute for Medical Research · Group Leader, UK Dementia Research Institute at Cambridge
Portrait: UK Dementia Research Institute
David Rubinsztein leads a lab at Cambridge that has spent over two decades studying autophagy — the process cells use to break down and recycle their own worn-out parts — and how failures in that process contribute to neurodegenerative diseases like Huntington's and Parkinson's.
In this study, his team asked a question that sounds almost architectural: does it matter where inside the cell a lysosome is sitting? They found that it does. Lysosomes parked near the cell's outer edge sit close to the signals that activate mTORC1, so mTORC1 turns on there. When nutrients run low, lysosomes cluster near the nucleus instead, and mTORC1 activity drops while autophagy ramps up. Moving lysosomes around, it turns out, is itself a way the cell fine-tunes growth versus recycling.
Milestones in the Atlas
| Year | Evidence | Study |
|---|---|---|
| 2004 | A | Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease RAV2004 Induced autophagy cleared toxic clumped proteins and improved symptoms in fly (rapamycin) and mouse (the rapalog CCI-779) models of Huntington's disease. |
| 2011 | M | Lysosomal positioning coordinates cellular nutrient responses KOR2011 Senior author on the discovery that lysosome positioning — spread toward the cell edge versus clustered near the nucleus — helps set how strongly mTORC1 activates and how efficiently autophagy proceeds. |
Co-authors in the Atlas
People with a profile here who share at least one study with David C. Rubinsztein.
- Viktor I. Korolchuk Showed that where lysosomes sit inside the cell tunes mTORC1 activity to nutrient supply. His Newcastle lab found that senescent cells can no longer switch mTORC1 off when nutrients or growth factors are withdrawn, and studies how autophagy and mitophagy decline with age