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Why neurons die? The role of monoamine oxidases (MAOs) in selective vulnerability of brain cells S&T55

  • School: School of Science and Technology
  • Study mode(s): Full-time / Part-time
  • Starting: 2022
  • Funding: UK student / EU student (non-UK) / International student (non-EU) / Fully-funded


NTU's Fully-funded PhD Studentship Scheme 2022

Project ID: S&T55

Ageing and age-related diseases are complex and involve a multitude of contributing factors; however, alterations in mitochondrial function are considered as one of the main drivers. Mitochondria have key roles in metabolism, calcium buffering and redox/protein homeostasis, controlling overall cellular health. Build-up of oxidised proteins plays a major role in age-related diseases and mitochondria are considered as an important source of reactive oxygen species (ROS). MAOs are located on the outer mitochondrial membrane and catalyse the oxidative deamination of dietary amines and monoamine neurotransmitters (e.g. dopamine, serotonin). Through catalytic by-products, MAOs contribute to hydrogen peroxide (ROS) and aldehyde generation. There are two isoforms, MAO-A and MAO-B. In the human brain, MAO-A is located largely to neurons whereas MAO-B is localised in glial cells. MAOs are involved in multiple neurodegenerative diseases and MAO inhibitors are used for the treatment of neurological disorders (e.g. Parkinson’s disease)1. However, MAOs expression is not limited to the brain; MAOs are also present in peripheral tissues and implicated in other pathological conditions. Through ROS production MAOs can contribute to DNA damage and instability and cell transformation. Indeed, recent studies indicate a role for MAO-A in progression of variety of cancers (including prostate, breast) and lymphangioleiomyomatosis making MAO inhibitors attractive drug targets2.

Our recent work has demonstrated that sustained ROS production by MAO-A in neuronal cells initiates mitochondrial fragmentation, activates autophagy and promotes mitochondrial clearance via mitophagy to maintain cell viability3. The effects of increased MAO-A levels however depend on availability of amine substrates and when substrates are in excess, cell viability is reduced. A variety of cellular stressors are known to induce MAO levels/activity but cell-type specific effects of a sustained increase in MAO levels and MAO generated ROS/aldehydes have not been investigated.
Using neuronal and glial cell models, this project will provide insight into how MAO levels influence signalling molecules in different brain cells and whether MAO contributes to cell specific vulnerability under stress and modify signalling between cells. Project will use a variety of techniques including mammalian cell culture (including human induced pluripotent stem cells), biochemical, molecular biology, proteomics/bioinformatics techniques and also involve high content live cell imaging/analysis and analysis of extracellular vesicles.

For informal inquiries: Dr Aslihan Ugun-Klusek

School strategic research priority

The proposed project aligns with the Centre for Health, Ageing and Understanding Disease.

Entry qualifications

For the eligibility criteria, visit our studentship application page.

How to apply

For guidance and to make an application, please visit our studentship application page. The application deadline is Friday 14 January 2022.

Fees and funding

This is part of NTU's 2022 fully-funded PhD Studentship Scheme.

Guidance and support

Download our full applicant guidance notes for more information.

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