Master of Bioinformatics, Structural Biochemistry and Genomics Thibaud Freyd disputerer for ph.d.-graden i helsevitenskap og vil offentlig forsvare avhandlingen:
“Allosteric modulation of GABAergic and glutamatergic metabotropic receptors”
Kort sammendrag av avhandlingen:
The GABAB receptor (GABAB-R) and the metabotropic glutamate receptor 1 (mGlu1-R) are drug targets for the treatment of CNS disorders and belong to the family C of G protein-coupled receptors (GPCRs). The first part of the thesis presents a successful screening campaign to identify new allosteric modulators of the GABAB-R. Using theoretical 3D models of the GABAB-R and information from known compounds, 55 potential allosteric modulators were selected from a database of 8 million commercial compounds. The experimental testing confirmed that 7 of the compounds act as allosteric modulators of the GABAB-R. The last part of the thesis describes a molecular dynamics study of mGlu1-R bound to different allosteric modulators. An intracellular water channel within the receptor was identified, and linked to the activity of the compounds. These results can be utilized in future design and development of drugs targeting GABAB-R and mGlu1-R. (Avhandlingen er tilgjengelig for utlån hos Seksjon for forskningstjenester frem til disputasdato)
Veiledere
Hovedveileder professor Ingebrigt Sylte Biveileder førsteamanuensis Kurt Kristiansen
Biveileder førstelektor Mari Gabrielsen
Bedømmelseskomiteen
Forsker Henri Xhaard, Division of Pharmaceutical Biosciences and Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Finland – 1. Opponent
Professor Matthieu Montes, Laboratoire Génomique, Bioinformatique et Applications, Frankrike – 2. Opponent
Førsteamanuensis Gerd Berge, Institutt for medisinsk biologi, Det helsevitenskapelige fakultet, UiT Norges arktiske universitet – leder av komité
Disputasleder
Professor Arnfinn Sundsfjord, Institutt for medisinsk biologi, Det helsevitenskapelige fakultet, UiT Norges arktiske universitet
Prøveforelesning over oppgitt emne holdes kl. 10.15, samme sted: “Comparing computational compound profiling methods when applied to the discovery of chemical probes or to the discovery of lead compounds”