Catalyst Award project spotlight: Dr Ruxandra Dafinca

Motor neurons are present in our brains and spinal cord, they allow us to move by sending signals from the brain to the muscles. Motor neurons do not physically touch each other, instead they are separated by small gaps called synapses.

It is at the synapse where messages are sent from one neuron to another through small packages. Similar to sending parcels in the post from one person to another, these messages are packaged in the first neuron at the “pre-synapse” and are then sent across the synapse to the next neuron. Once the next neuron receives the message packets, it responds by delivering the signal to the next neuron, until the signal reaches the muscle.

In MND, we know that this process at the synapse is impacted, which leads to messages not being sent between motor neurons and muscles, causing problems with movement and ultimately leading to motor neuron death. Through our 2024 Catalyst Award, Dr Ruxandra Dafinca will be aiming to understand more about why messages are not packaged properly at the pre-synapse in MND.

She will be looking at the pre-synapse of motor neurons using an advanced technique called “spatial proteomics”, a technology that allows scientists to identify different proteins, look at their quantity and also look at where exactly these proteins are located.

In all cells, including motor neurons, proteins are functional, which means they all have different jobs to do. The presence and location of different proteins in the pre-synapse is incredibly important to ensure the communication messages are packaged correctly, much like ensuring all of the people and different machines are present and working correctly during a production line.

If changes in the location of proteins at the pre-synapse can be identified in MND, this might reveal insights into why this packaging process is affected in MND.

Dr Dafinca told us: “Maintaining neuronal health relies on proteins being in the correct place in order to fulfill their function. We know that in motor neuron disease we have the mislocalisation of TDP-43 in 97% of cases, which highlights the importance of protein organisation and localisation within the cell, not just the amount that is present.”

The research carried out through this Catalyst Award will be the first to identify the location of all of the proteins at the pre-synapse in MND, this could help identify new targets for treatments. She explained: “We are lacking a clear comprehensive view on what other proteins are doing at the same time and where other proteins may be mislocalised that could then become key targets for developing new treatments”

You can check out Dr Dafinca’s project here.