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02 June 2023

£1.3 million MRC grant awarded to study neuronal signalling failure

The Medical Research Council (MRC) has awarded £1,310,130 to King's researchers for the project 'Structural and functional studies of the VAPB-PTPIP51 ER-mitochondria tethering proteins in neurodegenerative diseases'.

Chris Miller ER-mitochondria MRC Grant

The project 'Structural and functional studies of the VAPB-PTPIP51 ER-mitochondria tethering proteins in neurodegenerative diseases' will investigate a key protein-protein interaction that is responsible for the shared disease mechanisms of Alzheimer's and amyotrophic lateral sclerosis.

Alzheimer's disease and amyotrophic lateral sclerosis (ALS) are two major neurodegenerative diseases with no known cure. They have multiple pathological features contributing to complex disease pathogenesis. This complicates the effort into finding effective treatments. 

Signalling between the endoplasmic reticulum (ER) and mitochondria is essential for various vital physiological functions. Furthermore, the ER-mitochondria signalling is responsible for functions that are damaged in Alzheimer's disease and ALS. The signalling requires close physical contact between the two organelles, mediated by "tethering proteins" that recruit regions of the ER to the mitochondrial surface. One of the best-characterised tethers is the interaction between ER protein VAPB and mitochondrial protein PTPIP51. 

Research has observed that ER-mitochondria signalling, including the VAPB-PTPIP51 tethering, is disrupted in both diseases. This new project will focus on this important interaction, gaining information on the structure to facilitate drug designs to correct damaged tethers. Furthermore, researchers will look at factors that affect binding and study the cascade of events that leads to disease symptoms.

The funding has been awarded to Professor Chris Miller from the Department of Basic and Clinical Neuroscience (BCN) and his co-applicants — Dr Joe Atherton (Randall Centre for Cell & Molecular Biophysics at the Faculty of Life Sciences & Medicine), Dr Jackie Mitchell (BCN, IoPPN), Professor Wendy Noble (Visiting Professor, King's) and Dr Alessio Vagnoni (BCN, IoPPN). The grant starts on 1 October 2023 for a duration of 3 years.

I am grateful to MRC for the funding we have received to study a key mechanism that may explain two major neurodegenerative diseases, Alzheimer's disease and ALS. These two diseases are extremely complex, and finding a shared molecular mechanism has provided great hope that we will soon develop efficient treatments.

Professor Chris Miller, Professor of Molecular Neuroscience at King's College London

For more information, please contact Annora Thoeng (School of Neuroscience Senior Communications and Engagement Officer)

In this story

Christopher Miller

Professor of Molecular Neuroscience

Jackie Mitchell

Lecturer in In Vivo Modelling of Neurodegeneration