PhD Fellowship in Organic Chemistry / Radiopharmaceutical Chemistry in Denmark, 2018

Department of Drug Design and Pharmacology at the University of Copenhagen in Denmark is offering 3 three-year PhD fellowships in organic chemistry/radiopharmaceutical chemistry.

The PhD fellowships are financed by the EU via a MC-ITN-ETN action. As such, the PhD fellowships are a part of a training programme PET-AlphaSy consisting in total 15 PhD students located in 5 European countries (Denmark, Sweden, Netherlands, Germany, Belgium). The PhD fellowships will attend common training sessions, e.g. within radiopharmaceutical chemistry or imaging and have secondments at the corresponding partner universities. The fellowships are available from 1 December 2018 or as soon as possible thereafter.

The positions are conditional on receiving the grant from the EU. Currently, the University of Copenhagen is within the negotiation phase with the EU.

Nanomedicines have been proven to be beneficial in diagnosis and therapy. In vivo imaging studies with the help of labeled structures are crucial to develop new nanomedicinal based drugs. In this project, we will develop a new imaging method based on bioorthogonal chemistry. The tetrazine ligation will be used to establish a so called pretargeted imaging approach that will be applied to blood-brain-barrier (BBB) permeable antibodies. A set of tetrazines will be synthesized and evaluated in respect to reaction kinetics, ADME properties, BBB permeability and metabolism. Most promising compounds will be radiolabeled with fluorine-18 and subsequently evaluated in an in vivo system that will be developed within our MC-ITN-ETN network. The project is mainly organic chemistry focused and spiced up with radioactive work. BBB permeable antibodies will be provided from a small-medium sized enterprise, BioArctic, Sweden. In vivo evaluation studies will mainly be carried out at the Werner Siemens Imaging Center, Tuebingen, Germany. A 3 month stay abroad at both partners is requested.

Principal supervisor is Associate Professor, Matthias Herth, Department of Drug Design and Pharmacology, E-mail:  [email protected], Direct Phone: +45 93565414.

Pretargeted imaging displays a novel possibility to image targets with monoclonal antibodies (mAb) with improved imaging contrast and lower radiation dose. The tetrazine ligation is one of the most promising bioorthogonal reaction for pretargeted strategies. In this project, a blood-brain-barrier (BBB) permeable antibody will be functionalized selectively with trans-cyclooctene (TCO) functional groups. These TCO groups will enable the selective binding of radiolabeled tetrazines to the mAb in vivo via pretargeted chemistry. Tetrazines will be developed by PhD fellows within our MC-ITN-ETN network and blood-brain-barrier (BBB) permeable antibodies will be provided by H. Lundbeck A/S, Denmark. In particular, this project is focused on novel strategic ideas to increase the amount of TCOs per mAb without disturbing the biological integrity of the mAb. Organic chemistry, ADME studies and biopharmaceutical chemistry techniques are the basis of this project. In vivo evaluation studies will mainly be carried out at the Uppsala University, Sweden and mAb conjugation chemistry at H. Lundbeck A/S, Denmark. Minimum 3 month stay at both partners is requested.

Principal supervisor is Associate Professor, Matthias Herth, Department of Drug Design and Pharmacology, E-mail:  [email protected] , Direct Phone: +45 93565414.

Affinity determination, biodistribution and metabolism studies are crucial factors while developing new drugs. This project is embedded in the development of novel Positron-Emission-Tomography (PET) tracers and aims to 3H-label and evaluate prime candidates that will be developed within our MC-ITN-ETN network. These new entities will be used to study ADME and binding characteristics before PET studies are initiated. Small molecules as well as biomolecules will be target molecules and as such a broad set of labeling techniques and precursor and reference compounds syntheses will be the major task of this project. This project is a central part of our MC-ITN-ETN network and connects the work between 6 PhD studies mainly developing new drugs and 3 PhD students working to evaluate these structures. Industrial expert knowledge in respect to 3H-labeling will be provide by Novo Nordisk, Denmark. Evaluation studies will mainly be conducted at Stichting VUMC, The Netherlands. A 3 month stay abroad at both partners is requested.

Principal supervisor is Associate Professor, Matthias Herth, Department of Drug Design and Pharmacology, E-mail:  [email protected], Direct Phone: +45 93565414.

• The position as a PhD fellow is available for a 3-year period.
• Terms of appointment and payment accord to the agreement between the Ministry of Finance and The Danish Confederation of Professional Associations on Academics in the State and according to the rules and regulations laid down by European Union’s Horizon 2020 Marie Curie Initial Training Networks. The position is covered by the Job Structure for Academic Staff at Universities (2013).

As an applicant you must have:

The application, in English, must be submitted electronically by clicking APPLY NOW above for each project of interest.

Your application must include:

Deadline: applications close 30 September 2018