Universiteit Leiden

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This Week’s Discoveries | 22 March 2016

Tuesday 22 March 2016
Gorlaeus Building
Einsteinweg 55
2333 CC Leiden
De Sitterzaal

First Lecture

Title Getting personal: how genetic variations alter G protein-coupled receptor signaling
Speaker Julia Hillger (LACDR)

Julia M. Hillger is a PhD student in the Division of Medicinal Chemistry of the LACDR (Leiden Academic Centre for Drug Research). Her research focusses on understanding how personal genetic differences affect drug function, in particular for G Protein-coupled Receptors (GPCRs), by using a combination of bioinformatics and cellular assays on personal cell lines. Abstract Genetic differences between individuals that affect drug action form a challenge in drug therapy. This also applies to GPCRs, as they are the target for many of today’s medicines. However, few studies have addressed how genetic influences alter receptor function. To move towards the real-life situation in a single individual, it is essential to investigate receptor function in a more ‘personal’ setting. In this talk, I will present how we studied GPCR signaling in lymphoblastoid cell lines (LCLs), a well-established type of such a personal cell line, using a non-invasive, impedance-based label-free cellular assay. For proof-of-principle, we performed a pharmacological characterization of several GPCRs, among which the Cannabinoid receptor 2 (CB2). By comparing responses to a small library of compounds between individuals with different genotypes for the CB2 receptor, we were able to identify both compounds prone to personal differences and compounds with more robust effects suited for ‘blockbuster’ use. All in all, this study provides evidence that LCLs are a suitable model system to study genetic influences on GPCR responses and thereby contribute to personalized medicine.

Second Lecture

Title Genome folding translates physico-chemical signals to switch genes “on” and “off”.
Speaker Remus Dame (LIC)

Remus Dame is an associate professor in the section Macromolecular Biochemistry at LIC. Remus investigates the coupling of genome organization and genome activity and the factors that fine-tune these processes in bacteria and archaea. He studies the proteins involved in vitro as well as in vivo using state-of-the-art biochemical and biophysical approaches. He was awarded a VICI grant from NWO last month.

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