Neuroscience and disease: Action, interaction and modulation of the AMPA receptor complex
AMPA receptors (part of the ionotropic glutamate receptor family) are essential for basic neurotransmission and underlie expression of synaptic plasticity. They have also been implicated in pathology of neurodegenerative diseases such as Alzheimer’s. Associated auxiliary proteins families (TARPs and cornichons) compliment the core subunits of the AMPA receptor (GluA1-A4), modulating both functional and trafficking properties of the core receptor and thus synaptic properties. Importantly, degree and type of modulation depend upon the precise combination of AMPA receptor subunits and auxiliary protein. The proposed project will have a number of interlinking and complimentary lines of research:
• To examine the role of chaperones, both small chemical and auxiliary proteins, to influence the recalcitrant trafficking of specific AMPA receptor combinations.
• To examine the proteins interacting with the auxiliary subunits which, in turn, will influence the AMPA receptor complex and its functional properties.
• To clarify if there is a specific and direct interaction between the larger AMPA receptor complex (AMPA receptor plus auxiliary proteins) and the amyloid precursor protein family (APP, ALPP-1 and -2).
The student will learn important laboratory technical methodologies such as cell culture and transfection, molecular biology, confocal microscopy, protein purification, immunochemical analysis and mass spectroscopy approaches. Further, the ability to correctly analyse and critically assess the limitations of such. They will be encouraged to join learned societies (e.g. The Biochemical Society and British Neuroscience Association), to participate in their scientific meetings and professional development workshops. Thus, gaining experience in presentation, communication and networking. The student will also be encouraged to prepare manuscripts for publication in the peer-reviewed literature. This will be aided by their participation in the University Graduate School and Faculty Doctoral Research Development Programme. Promoting the development of important skills for future career advancement both with academia and outside of such.
The Studentship consists of a fee waiver and a stipend of £16,000 per annum. Successful candidates will be expected to undertake some teaching duties.
Coleman SK, Hou Y, Willibald M, Semenov A, Möykkynen T and Keinänen, K (2015)
Aggregation limits surface expression of homomeric GluA3 receptors. J Biol Chem (under
Möykkynen T*, Coleman SK*, Semenov A, Keinänen K (2014) The N-terminal domain
modulates α- amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor
desensitization. J Biol Chem 289, 13197-13205.
Semenov A, Möykkynen T, Coleman SK, Korpi ER, Keinänen K (2012) Autoinactivation of
The stargazin-AMPA receptor complex: subunit-dependency and independence from
physical dissociation. PLoS One 7, e49282. doi: 10.1371/journal.pone.0049282.
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