Funded Research Projects


Defining the role of the motor axon translatome in SMA pathogenesis

Principal investigator(s):
Professor Tom Gillingwater
University of Edinburgh
Grant Type:
Operating Grant
Start Year:
2 years
Call number:

Professor Tom Gillingwater

Professor Tom Gillingwater, from Edinburgh University, has been granted an SMA Europe award to investigate how SMN regulates the process of translation in vivo (the end-stage of the process whereby cells convert DNA into working proteins).

In Focus


SMA is caused by low levels of a single protein called SMN. What this SMN protein does is still not fully understood and therefore nor is it understood why low levels of it lead to specific clinical features of SMA, including the breakdown of motor neurons.

What are the researchers aiming to do and why?

This project will build on exciting preliminary work revealing that SMN plays a major role in regulating translation (the end-stage of the process whereby cells convert DNA into working proteins). By taking advantage of state-of-the-art genetic technologies, the team will explore how SMN regulates the process of translation in vivo. This project will therefore generate important new insights into how and why motor neurons break down in SMA.

How will this work benefit patients?

The current clinical trials in SMA which target SMN protein levels are showing great promise. Indeed, one such treatment has just been approved to treat all SMA patients in Europe and the US. Whilst this represents an important milestone for SMA research it is also clear that these strategies fall significantly short of representing a cure for SMA. Therapies that target other/additional cellular and molecular pathways will likely be required to treat the full range of phenotypes and pathology observed in SMA patients across the life-span.

A further understanding of the pathogenic basis of SMA is therefore necessary to identify new therapeutic targets with disease-modifying potential that can be used for such combinatorial therapy approaches. By unravelling the motor neuron process of protein translation in both SMA and control mice, the team will reveal the first detailed picture of molecular changes occurring in motor neurons underlying disease pathogenesis in SMA. These new insights will allow future therapies to be more finely tailored to the cellular and molecular processes that are most vital for motor neuron survival.