Dr G H Doherty
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
About the Project
A subset of ALS patients, as well as TDP-43 mice and SOD1 overexpressing mice (used to model ALS) are hypermetabolic, showing increased resting energy expenditure and decreased bodyweight. It has recently been shown that mice deficient in the anti-obesity hormone leptin show decreased motor symptoms when SOD1 is overexpressed, implying that leptin-deficiency-induced hypometabolism is protective against ALS-like symptoms1. However, leptin per se plays crucial beneficial roles in the development and maintenance of the CNS2,3. Therefore this project aims to determine the consequences of leptin-deficiency for motor neuron viability, electrophysiology and biochemistry using both in vitro and transgenic approaches. Specifically we seek to determine whether neurons that are genetically manipulated to lack the leptin receptor, or which are exposed to leptin superantagonists4, exhibit biochemical, electrophysiological or morphological aberrations which would suggest that leptin amelioration is not a suitable means of inducing hypometabolism. The successful applicant would be given full training and experience in cell culture, electrophysiology and biochemistry representing an excellent opportunity to gain experience in multiple empirical techniques applicable to a future career in biomedical research.
Prerequisites
B.Sc. or masters in Biochemistry, Neuroscience or related discipline. Previous experience of cell culture, electrophysiology or biochemistry
The project is a part of SPRINT-MND/MS, a new Scotland-wide PhD scheme for research into motor neurone disease and multiple sclerosis. Projects, encompassing a wide range of topics including laboratory, clinical, and social sciences, are available at Aberdeen, Dundee, Edinburgh, Glasgow and St Andrews Universities. This exciting initiative provides a great opportunity for budding researchers in any field related to MND or MS to join Scotland’s network of world-leading scientists and health professionals. Find more information here: http://www.edinburghneuroscience.ed.ac.uk/edneurophd/sprint-mndms-phd-programme
Funding Notes
Studentships are for three years and include a standard non-clinical stipend*, UK/EU fees* and an allowance for consumables and travel. The cohort of SPRINT students will also be offered opportunities to attend clinics and meet patients, undertake ‘taster’ placements in a different field, and participate in public engagement and researcher networking events.
*Clinical and/or non-UK/EU applicants are eligible to apply. However, because any shortfall in stipend or fees must be met by the supervisory team, written agreement from the supervisor must accompany the application.
References
1. Lim MA, Bence KK, Sandesara I, Andreux P, Auwerx J, Ishibashi J, Seale P, Kalb RG. Genetically altering organismal metabolism by leptin-deficiency benefits a mouse model of amyotrophic lateral sclerosis. Hum Mol Genet. 2014 Sep 5;23(18):4995-5008.
2. Doherty GH, Oldreive C, Harvey J. Neuroprotective actions of leptin on central and peripheral neurons in vitro. Neuroscience. 2008 Jul 17;154(4):1297-307.
3. Malekizadeh Y, Holiday A, Redfearn D, Ainge JA, Doherty G, Harvey J. A Leptin Fragment Mirrors the Cognitive Enhancing and Neuroprotective Actions of Leptin. Cereb Cortex. 2016 Sep 6. [Epub ahead of print]
4. Gertler A, Elinav E. Novel superactive leptin antagonists and their potential
therapeutic applications. Curr Pharm Des. 2014;20(4):659-65.
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