Advanced linker platform for increased blood-csf barrier drug transport

Basic mentor

Mette Rosenkilde, professor, Dept Biomedicine, UCPH.

Clinical mentor

Gitte Moos Knudsen, professor, Dept neurology, Rigshospitalet.

Mentor 3

Katrine Qvortrup, associate professor, DTU. 

Framework

This project will be performed in a unique translational environment bridging basic and applied neuroimaging across two of Denmarks forefront neuropharmacology groups. Dr. Rosenkilde has vast experience in molecular and translational pharmacology within G protein-coupled receptors. Dr. Knudsen is a pioneer in PET imaging and the head of The Neurobiology Research Unit (NRU) at Copenhagen University Hospital. Dr. Qvortrup is experienced within advanced bioconjugation technologies for protein modification. This setting allows the selected candidate to collaborate with a broad range of experts in brain diseases, neuroimaging, modelling and development of new methods for increase drug availability in the brain. The successful candidate will also have direct interactions with chemistry and radiochemistry groups at SUND, KU and at DTU. The highly interactive working environment with input from scientists from multiple fields will contribute to the interdisciplinary development of the project.

Project synopsis

Brain inaccessibility of drug candidates for diagnostic radioligands or for pharmacological treatment of brain disorders is a major challenge. Multiple drugs for treatment of brain disorders, with high potency at the molecular level, have failed due to low penetrance across brain barriers. With this project, we will in a multidisciplinary setting develop and test novel linkers that enable the transfer of small or large molecules across the blood- cerebrospinal fluid. Test of drug affinity will be carried out in cell cultures. Proof-of-concept will be made in rodent or pig studies with well-known radioligands and neuroimaging that allows for determination of the pharmacokinetics of drugs targeting brain receptors or proteins. Next, we wish to test the approach with alpha-synuclein binding compounds in animal models of Parkinsons Disease. The goal is to identify novel ways of getting radioligands and pharmacological compounds into the brain for improved diagnostics and better therapies.

Fellow candidate

  • Neuroscience, pharmacology, biochemistry, or radiochemistry

  • PhD within a relevant research field, eg., neurobiology or pharmacology

  • International experience

  • Experience with animal studies and/or neuroimaging

  • Experience with tissue culturing

Contact

Basic mentor Mette Rosenkilde: rosenkilde@sund.ku.dk