Professor Linda Greensmith founded the Graeme Watts Laboratory at UCL Queen Square Institute of Neurology (IoN) in London in 1999, supported by funds left to Brain Research UK by the family of Graeme Watts, who died of motor neuron disease (MND). Graeme’s family left a bequest in his name to fund research to improve the basic understanding of MND and to develop therapeutic strategies.
No-one at the IoN was strongly focused on MND at that time and Professor Greensmith was recruited to set up a lab to take forward research into this devastating disease.
Twenty-seven years on, she has had remarkable success. The Graeme Watts Laboratories are now at the forefront of research into MND; drug compounds that started life there are now undergoing clinical trials; and researchers trained there have gone on to successful careers inside and outside UCL. We continue to support research in the Graeme Watts Laboratories using funds from the endowment established in Graeme’s name, including programme grants on Targeting the heat shock response in ALS and Overcoming Paralysis using a Therapeutic Interface to Control muscles ALS (OPTICALS), and the post of Laboratory Manager.
MND describes a group of diseases affecting the nerves (motor neurons) in the brain and spinal cord that control the muscles. These are fatal, rapidly progressing conditions that rob patients of their ability to walk, talk and eventually to swallow and breathe.
There is no cure for these diseases. They kill a third of patients within a year and more than half within two years of diagnosis.
Read more: About motor neuron disease
The Graeme Watts Laboratory Manager post was established in 1999 at the start of the Graeme Watts Research Laboratory, and is central to the smooth running of the current Laboratories. The Watts research group is a multidisciplinary team composed of senior and junior postdocs as well as PhD students, clinical fellows and Masters and BSc students. This group come from a variety of backgrounds, and all require training in laboratory skills. Therefore, in addition to the key role of managing all aspects of the Laboratories, the Laboratory Manager is responsible for the induction and training of all new members of the group in core and specialised research techniques. The current post-holder also undertakes pilot research projects and specialised aspects of collaborative research projects.
In 1999, with funding from the Graeme Watts Endowment, Professor Greensmith took on the challenge of setting up a new laboratory for research into MND.
The resulting Laboratories have played a huge role in developing research capacity in MND, with Professor Greensmith herself having train 43 PhD students (34 as primary supervisor), 21 postdocs and many more Masters and BSc students.
Team members benefit from the close physical proximity to the National Hospital for Neurology and Neurosurgery, and enjoy good collaborative links with the clinicians there, which is unusual for a discovery science laboratory but enormously important in ensuring that the work has translational relevance.
One of the key pathological features of MND is the abnormal clumping of proteins within motor neurons. This clumping, called protein aggregation, is also a characteristic feature of most other neurodegenerative diseases, but it affects different types of neurons in different diseases.
In some of the early research undertaken in the Graeme Watts Laboratories, Professor Greensmith’s team demonstrated that strategies that target protein aggregation in ALS may be a possible therapeutic strategy for ALS. The team developed a drug that they showed could work in both cellular models of ALS, where neurons are grown in a dish (in vitro), and in their mouse models of ALS (in vivo).
Their results showed that treatment with a compound called Arimoclomol prevented protein aggregation in neurons and as a result improved the disease in ALS mice. More specifically, Arimoclomol was shown to act by boosting a mechanism present in all cells called the heat shock response, which normally protects cells under stress but is less effective than normal in ALS. However, Arimoclomol was not originally designed or optimised to target this protective mechanism or to act on motor neurons within the central nervous system. Professor Greensmith’s team therefore wanted to understand more about the heat shock response and how it is changed in ALS, with the overall aim of identifying compounds that might more effectively target the heat shock response in ALS or other types of MND, either alone or in combination with other promising therapies.
We therefore funded a programme grant to enable Linda and her team to investigate this, the results of which can be found here.
Separately, in a paper published in 2014, Professor Greensmth’s team reported the findings of a novel approach developed to restore function of paralysed respiratory muscles in MND patients. This approach used optogenetics, a technique that involves genetic modification of motor neurons so that they can be stimulated by light and then controlled via an optical pacemaker.
This has now led to a second programme grant to enable Linda and her team to investigate the potential for using optogenetics to overcome ALS, which is ongoing.
Out of the tragic death of Graeme Watts, and the incredible generosity and foresight of his family, has grown more than two decades of game-changing research into motor neuron disease. As set out above, this funding has had a tremendous impact on research capacity in MND – creating a new hub at UCL, with a major focus on training. This funding has also seeded many millions of pounds worth of grants from other sources.
Since 2013 the Lab has published 91 peer-reviewed papers and has been awarded a total of 52 research grants, with a total value of more than £17.5M. In addition, Linda is currently a Co-PI on several large collaborative grants including The UK MND Research Institute: Phase 2 (2026-2030) = £5M and NIHR: EXPERTS-ALS Project (2023-2027), a new clinical trial platform for ALS = £4.8M.
There’s not many groups that get things through from working in cells to working in mice and then getting them into the clinic. That translation, hitting each part of the translational pipeline, is really nice and is very rare.
- Professor Linda Greensmith
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