A three-year PhD fellowship has become available within a project based upon positive allosteric modulation of kainate receptors (KARs). The employment as PhD fellow is full time and for 3 years. The PhD fellowship is financed by the Independent Research Fund Denmark – Health Sciences and headed by Professor Jette Sandholm Kastrup. The fellowship is available from 1 October 2020 or as soon as possible thereafter. The PhD project is performed in collaboration with University of Liege, Belgium and University of Bordeaux, France.
About the project
Project title: Positive allosteric modulation of kainate receptors - an unexplored therapeutic potential for treatment of CNS diseases
The PhD student will take part in an ambitious interdisciplinary project spanning pharmacological screening for positive allosteric modulators (PAMs) of KARs, two-electrode voltage clamp and patch-clamp electrophysiology, radiolabel-receptor binding and structure determination by X-ray crystallography.
The overall aim of the PhD project is to find the first high affinity, high efficacy and preferably selective PAM acting on the KARs and to examine the role of KAR PAMs at hippocampal neurons.
KARs are activated by the major excitatory neurotransmitter glutamate. They are localized both pre- and postsynaptically and thus, in addition to a direct excitatory effect, also play a role in modulating the activity of neuronal networks. KARs are involved in CNS diseases such as epilepsy, depression and schizophrenia, and therefore the understanding of the molecular function of these receptors is essential for unravelling their potential as targets for treatment of these pathologies.
We recently reported the first small molecule PAMs that bind to and strongly potentiate KARs (Larsen et al., Mol. Pharmacol., 2017). This now opens an entire new research area with a focus on optimizing the potency, affinity, efficacy and selectivity of the KAR PAMs.
The PhD fellow will manage and carry out the research project, participate in the education and guidance of undergraduate and graduate students, and write scientific publications.
• Qualifications corresponding to a master’s degree in pharmacy, pharmaceutical sciences or relevant area prior to the starting date
• A solid background in pharmacology
• A demonstrated ability to learn new methods and research areas
• Acceptance with harvesting brain tissue from mice
• An ability to work both independently and in teams
• Fluency in English and excellent communication skills
• Knowledge of ionotropic glutamate receptors
• Cell culturing
• Two-electrode voltage clamp or patch-clamp electrophysiology
• Radiolabel binding assays
• Microtitre plate-based fluorescence assays
• Expression of proteins in E. coli and purification
• Protein crystallography
• Analysis of molecular structures and interactions
For more information about this PhD studentship, including how to apply, see the University website.