Projects

Ongoing projects

Investigating the causes of V1 interneuron dysregulation in early stages of ALS using spatial transcriptomics

The loss of synaptic inputs detected in pre-symptomatic ALS mice might be due to alterations occurring either in the inhibitory interneurons or in the motor neurons. To understand the temporal dynamics of this event, spatial transcriptomics is applied to investigate the role of motor neuron and interneurons during degeneration. This project is conducted at University of St Andrews in collaboration with the Department of Molecular Medicine (MOMA) at Aarhus University Hospital. It is funded by the MRC UKRI, the RS Macdonald Trust, the EMBO Young Investigator Program and the University of St Andrews.

Facing dementia: investigating early onset of Frontotemporal Dementia via Artificial Intelligence

Artificial intelligence (AI)-based methods are applied to identify emotions in a mouse model of FTD in response to positive or adverse stimuli delivered by a virtual reality (VR) interface. Correlations between early FTD symptoms and alterations in the activity of neural circuits found in the frontal and prefrontal lobes of the brain are investigated to find new targets for treatment. This project is conducted at University of St Andrews in collaboration with Dr Raghavendra Selvan at the Machine Learning Section, Department of Computer Science (University of Copenhagen). It is funded by the University of St Andrews, the St Leonard’s Postgraduate College, the Royal Society and the RS Macdonald Trust.

Amyotrophic Lateral Sclerosis, treating the circuit behind the disease

The overall purpose of this project is to develop a translational gene therapy. This project is conducted at University of St Andrews in collaboration with the Newcastle Brain Tissue Resource (UK). This project is funded by the MRC UKRI. More information about the project can be found here.

Modeling the temporal dynamics of neural circuit degeneration in ALS

This project uses a computational model to investigate findings from our lab indicating differential temporal dynamics in inhibitory and excitatory spinal circuit degeneration in ALS. The model aims to find a therapeutic window for intervention and rescue of the neural network controlling motor neurons. The project aims to refine the number of experimental animals used in research. The findings will be validated in ALS mice, leading to the understanding of when the use of synaptic stabilisers can affect disease progression. This project is conducted in collaboration with Dr Jessica Ausborn at Drexel University (USA). The project is funded by the Louis-Hansen Foundation, the Lundbeck Foundation seed grant and the University of St Andrews.

Identifying novel targets for the treatment of Alzheimer’s and Motor Neurone Disease

This project is conducted in collaboration with the Gunn-Moore group at University of St Andrews and explores the role of the Willin/FRMD6 gene as a new biochemical target involved in motor neuron disease (MND) pathogenesis. The Willin/FRMD6 encodes for a protein that the Gunn-Moore group initially discovered and was shown to be an upstream modulator of the “Hippo” biochemical pathway that has recently been shown to be involved in Alzheimer’s disease (AD) progression. Using spatial transcriptomics and animal models of MND, we uncovered that the Willin/FRMD6 gene is downregulated in motor neurons during early stages of disease. We are investigating this new biochemical pathway using bioinformatics and human postmortem tissue. The project is funded by the St Leonard’s Postgraduate College and the University of St Andrews. the St Leonard’s Postgraduate College

Completed projects

Treating ALS disease by rescuing interneuron-motor neuron synaptic connectivity

In ALS, spinal inhibitory interneurons lose their connections to motor neurons during early pre-symptomatic stages before motor neuron death. The loss of these synaptic inputs appears to be restricted to vulnerable motor neurons and triggers pathological events such as, increased intracellular Ca2+ levels, ER stress and cell death. This project aims to rescue the synaptic connections between interneurons and motor neurons in an ALS mouse model by gene therapy, to understand if this alone could reverse the symptoms. This project is conducted in collaboration with the Verhaagen laboratory at the Netherlands Institute for Neuroscience and funded by the Lundbeck foundation, the Danish Society for Neuroscience-Lundbeck scholarships, University of Copenhagen and University of St Andrews. The results are published in Nature Communications.

Dissecting the role of inhibitory and excitatory spinal interneurons in ALS pathology

This project aims to clarify the contribution of inhibitory and excitatory spinal interneurons to ALS pathophysiology. Here, multiplexing detection of transcripts is combined with machine learning-based cell segmentation and bioinformatic analysis to understand the degeneration of specific neural circuits within the spinal cord. This project is conducted at University of Copenhagen and University of St Andrews in collaboration with Prof. Ole Kiehn, Dr. Raghavendra Selvan and ACD Bio. It is funded by the Lundbeck foundation (IA), the Novo Nordisk foundation (OK), the Louis-Hansen Foundation (RM), ACD Bio and the Department of Neuroscience. The results are published in Science Advances and shared in a press release from the University of St Andrews.