EMC-2024-1_Allodi: Investigating the role of Munc 13-1 in Amyotrophic lateral sclerosis


   Centre for Clinical Brain Sciences

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  Dr Ilary Allodi, Dr Cordelia Imig  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

THIS PROJECT WILL BE BASED AT THE UNIVERSITY OF ST ANDREWS

This project is on offer as part of the studentship scheme of the Euan MacDonald Centre for Motor Neuron Disease Research. The Euan MacDonald Centre is a multi-disciplinary network of MND researchers across Scotland. A choice of six projects is on offer now for a start date in Autumn 2024, at the University of Edinburgh, St Andrews or Dundee. For more information see www.euanmacdonaldcentre.org/phd-scheme. Euan MacDonald Centre students join our network of >200 MND researchers across Scotland and will have the opportunity to meet people living with MND, participate in academic and public engagement events led by the Centre. To view all the projects offered under this scheme please search for reference numbers EMC-2024-1 to EMC-2024-6. 

Alterations in synaptic connectivity can trigger diseases affecting the motor system, including Amyotrophic Lateral Sclerosis (ALS). Our previous work showed that synapses undergo modifications and depletion in presence of ALS-triggering genetic mutations. Munc 13-1 is a key protein present at synaptic level playing a pivotal role in the maintenance of connectivity between neurons. Munc 13-1 was found downregulated in presence of the TDP43 mutation, becoming an important target for diseases affecting the motor system. The present project aims to elucidate the role of Munc 13-1 in ALS. Here, downregulation of Munc 13-1 will be performed in inhibitory or excitatory neurons utilising a cre-lox strategy. A similar approach has been previously used to investigate the role of Munc 13-1 in dopaminergic neurons and the crossed mice resulted viable. The phenotype of the newly generated mice will be investigated by machine learning-based analysis of motor functions. Moreover, electrophysiological properties of inhibitory and excitatory neurons will be investigated in ex vivo preparation to further understand the impact of Munc 13-1 downregulation on the spinal motor circuits. Finally, anatomical analysis will be performed to assess potential synaptic changes and cell loss in the Munc 13-1 deficient mice. We anticipate that this project will unravel the role of the Munc 13-1 in ALS.

Suitable first degree subjects: Neuroscience, molecular biology, data science. For this project the desirable skills and experience are: -Background in neuroscience -Genuine interest in neurodegenerative diseases, behavioural analysis, and electrophysiology -Previous training in behavioural analysis, transgenic mice handling -Previous training in molecular biology techniques and microscopy -Basic knowledge of R/Python -Fluent in English (written and spoken) -Ability to perform experiments and to interpret results -Willingness to learn new techniques -Well-organized, self-motivated, result-oriented, and capable of working independently in a collaborative setting -Strong background in ALS or other neurodegenerative disorders will be considered a plus. 

Biological Sciences (4) Computer Science (8) Medicine (26)

Funding Notes

The studentship comprises 42 months (3.5 years) stipend payments at the standard UKRI rate, tuition fees and an allowance of £10K per year for three years for consumables and travel. The studentship is open to applicants worldwide. Students will register for the most appropriate degree programme at the University where the project is being offered. It is the applicants’ responsibility to ensure they meet the eligibility requirements for postgraduate study at their chosen University, in terms of academic achievements and English language proficiency.

References

Allodi I et al (2021) Nature Communications doi: https://doi.org/10.1038/s41467-021-23224-7
Banerjee A, Imig C et al (2022) Neuron doi: 10.1016/j.neuron.2021.10.028
Mora S et al (2022) bioRxiv doi: https://doi.org/10.21203/rs.3.rs-2613071/v1
Montañana-Rosell R et al (2023) bioRxiv doi: https://doi.org/10.1101/2023.09.17.558103
Mora S & Allodi I (2023) Frontiers in Neural Circuits https://doi.org/10.3389/fncir.2023.1208876

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