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This doctoral candidate position is open within the context of the Doctoral Network (DN) project MC4DD (Macrocycles for Drug Discovery) within the framework of the Marie Skłodowska-Curie Actions (MSCA).

This PhD position is hosted at AbbVie Germany GmbH & Co. KG, in 67061 Ludwigshafen, Germany, with 2 secondments for 3 months each at University of Torino (Italy), and at Technical University Darmstadt (Germany).

Responsibilities:

• Define a set of macrocyclic model substrates spanning a range of key structural and physicochemical parameters;
• Generate in vitro data on permeability and efflux substrate properties using cellular models: Caco2, MDCK (+MDR1 & BCRP efflux transporters)
• for a selected subset of compounds, use mouse PK cassette studies to determine in vivo brain/plasma ratio, absolute brain and plasma compound levels, and determine free fraction in brain homogenate to calculate Kp,uu,brain.
• Determine the desired property space for brain penetrant macrocycles by analyzing relationships between endpoints determined above, e.g. SAR (relationship between structural or physicochemical properties and in vitro permeability / efflux or in vivo brain penetration), and in vitro – in vivo (relationship between in vitro permeability / efflux and and in vivo brain penetration)
• Measurement of chameleonicity of brain-permeable MCs (during 3-months secondment at University of Torino, Italy)
• Analysis of Structure-Activity-Relationships (SAR) of brain-permeable MCs (during 3-months secondment at Technical University Darmstadt, Germany)

• MSc or equivalent in Biology, Pharmaceutical or Life Sciences
• Research experience in biological, biochemical or related fields
• Scientific interest, dedication to research, and career goal to work in drug discovery
• Appreciation for interdisciplinarity and proactive drive to collaborate across fields
• Proficiency in English, good communication skill and social competence
• Hands-on experience with in vitro assays, ideally with cell culture systems
• Hands-on experience with animal experiments, ideally through participation in a FELASA course, and willingness to perform in vivo studies in mice and/or rats (e.g. dosing, and blood/ tissue sampling)
• Ability and willingnes to work independently in an industry environment

Eligibility criteria

• Supported researchers must be doctoral candidates, i.e. not already in possession of a doctoral degree at the date of the recruitment.

• Mobility Rule: researchers must not have resided or carried out their main activity (work, studies, etc.) in Germany >12 months in the 36 months preceding their recruitment date.

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