Active Brain & Nervous System Cells, Biochemistry & Physiology

Understanding the role of organelle contact networks in neuronal health and disease

Funder Wellcome Charity-funded
Recipient organisation University of Cambridge
Funding £3.4M
Period Feb 2024 — Feb 2032

In plain English

AI plain-English summary

Every neuron in the brain runs its own internal logistics network, shuttling fats and other molecules between its organelles at specialised contact points, and this project will map how those exchanges keep neurons firing and what happens when they break down in disease. The problem is that while scientists know organelles touch each other to swap materials, they do not understand the molecular tethers that control where and when these contacts form, nor how the exchange of key biomolecules supports action potentials and synaptic vesicle release. Without this knowledge, neurodegeneration remains a black box—we see cells die but cannot trace the upstream failures. This is fundamental science. The lab will use custom imaging, proteomic, and lipidomic tools to identify the machinery that regulates contact sites in healthy neurons and then track how those processes are corrupted during neurodegeneration. If successful, the work will reveal the wiring diagram of the organelle communication network inside nerve cells. That deeper understanding could eventually point to new targets for therapies in diseases like Alzheimer’s or motor neuron disease, where organelle dysfunction is suspected but poorly understood. Past fundamental discoveries about organelle biology have already reshaped how we think about metabolic and neurological disorders.

View original technical description
Deciphering how neuronal transmission and circuit formation enable movement, thought, and behaviour, represents one of the central challenges of research today. Much of this work has focussed on characterising communication between neurons. However, within each individual neuron is an equally complex communication network – between subcellular organelles. Membrane contact sites between organelles are now recognised as key sites that enable the rapid transfer of biomolecules across the organelle interaction network and thereby facilitate successful action potential firing, synaptic vesicle release, and synaptic membrane organisation. However, the machinery and mechanisms that regulate contact sites to enable neuronal function remain unknown. My lab will deploy the unique imaging, proteomic and lipidomic tools that I have developed to explore the role that organelle contacts play in neuronal transmission and circuit formation, and discover how these processes are compromised during neurodegeneration. To achieve this we will investigate: - The role of molecular tethers in dictating where and when contact sites form between different organelles in healthy and diseased neurons - The mechanisms and machinery underpinning the exchange of key biomolecules at neuronal organelle contact sites, and how these processes are corrupted during neurodegeneration. - How these processes converge to enable neuronal transmission and circuit formation

View the original record at the funder ↗

Researchers

Jonathon Nixon-Abell (EPMC Awardee)

Related Research

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Original classification

Career Development Award

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