In Roche's Pharmaceutical Research and Early Development organisation (pRED), we make transformative medicines for patients in order to tackle some of the world's toughest unmet healthcare needs. At pRED, we are united by our mission to transform science into medicines. Together, we create a culture defined by curiosity, responsibility and humility, where our talented people are empowered and inspired to bring forward extraordinary life-changing innovation at speed.
This position is located in ADME, a chapter within the PS function, where the fate of new chemical entities and biologics is a primary focus. The ADME Chapter works throughout all stages of compound development, from lead optimization to candidate selection, all clinical development phases to filing of new drug applications. We closely collaborate with our therapeutic areas and functions to convert hypotheses into innovative therapeutics.
Project aims:
The fraction of a drug metabolised by specific cytochrome P450 (CYP) enzymes relative to total hepatic metabolism (fm,CYP) is one of the major factors determining the magnitude of drug interactions and the impact of polymorphisms on total clearance in clinics. In alignment with Drug-Drug Interaction (DDI) assessment guidelines issued by regulatory agencies, in vitro reaction phenotyping approaches to estimate fm, CYP mainly involves 1) evaluation of the inhibitory effects of P450 selective chemical inhibitors on the oxidative metabolism in pooled human liver microsomes (HLM) and/or 2) extrapolation of the metabolic turnover measured in recombinantly expressed CYP enzymes to that in HLM.
The primary objective of this project is to verify chemical inhibition CYP phenotyping and recombinant enzyme study results using a variety of probe substrates and control inhibitors for major CYP enzymes to obtain greater insight into the clinical translatability of the in vitro fm, CYP data.
Project goals:
You will learn about P450 reaction phenotyping approaches, and insights into the potential limitations being developed to circumvent these
You will gain hands-on experience in quantitative LC-mass spectrometry
You will understand the importance of victim DDI risk assessment in drug development
Who you are:
You are studying in an M.Sc. program in biochemistry, pharmacology and/or (molecular) biology. A strong interest in evaluations of enzyme targets and drug metabolism assays in vitro is an advantage.
You are familiar with common digital tools for experimental planning, execution, evaluation, data archiving and reporting.
You have strong communication skills and the ability to work in a team. Proactive and strategic thinking style to promote the project is preferred.
You are able to work independently with minimal supervision and have the ability to solve problems in an innovative way.
Proficiency in English is required, and ability to communicate in German or French is an asset.
Details of the Internship
Start date: as soon as possible
Duration: 12 months
To be considered, please send us your complete application merged into one PDF, including
Please have a look at our Q&A section for more information: https://careers.roche.com/global/en/faq
We look forward to receiving your application!
