PhD Ghrelin-based therapies for ALS – understanding mechanisms of action

Vacancy Reference Number

2019-SPRINT-02

Closing Date

7 Jan 2019

Address

University of St Andrews

Ghrelin is an endogenous growth hormone secretagogue and neuropeptide that enhances food intake and appetite, and which signals via the GHSR1 receptor. Patients with ALS have markedly reduced circulating levels of ghrelin, despite having a lower body mass index than age-matched controls1. This suggests that impaired ghrelin signalling may contribute to disease progression.

In models of neurodegeneration ghrelin protects against mitochondrial dysfunction and degeneration2, reduces neuroinflammation3, and crucially for this study, protects against motor neuron cell death in vitro4. As cytotoxicity, neuroinflammation and impaired redox balance are all implicated in ALS, a thorough evaluation of the effects of GHSR1 agonists is now essential.

This project aims to investigate the effects of GHSR1 agonists on motor neurons. Specific objectives are:

1. To identify whether ghrelin modulates the production of reactive oxygen species in motor neurons and whether they modulate expression and activity of antioxidant defences

2. To define the effects of ghrelin on motor neuron mitochondrial dynamics and function

3. To understand whether ghrelin can modulate the physiological properties of motor neurons

This project will be jointly hosted at the Universities of St Andrews (cell and molecular biology) and Dundee (electrophysiology).

The student will enter into established research teams who have published together on other neurodegenerative conditions5. However, the student will be exploring a novel area of collaboration between the two labs.

For more information and to apply, click here