Identification of odorant-receptor interactions by global mapping of the human odorome.
The human olfactory system recognizes a broad spectrum of odorants using approximately 400 different olfactory receptors (hORs). Although significant improvements of heterologous expression systems used to study interactions between ORs and odorant molecules have been made, screening the olfactory repertoire of hORs remains a tremendous challenge. We therefore developed a chemical systems level approach based on protein-protein association network to investigate novel hOR-odorant relationships. Using this new approach, we proposed and validated new bioactivities for odorant molecules and OR2W1, OR51E1 and OR5P3. As it remains largely unknown how human perception of odorants influence or prevent diseases, we also developed an odorant-protein matrix to explore global relationships between chemicals, biological targets and disease susceptibilities. We successfully experimentally demonstrated interactions between odorants and the cannabinoid receptor 1 (CB1) and the peroxisome proliferator-activated receptor gamma (PPARγ). Overall, these results illustrate the potential of integrative systems chemical biology to explore the impact of odorant molecules on human health, i.e. human odorome.
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
Karine
K
Audouze
Centre des Sciences du Goût et de l'Alimentation, UMR6265 CNRS, UMR1324 INRA, Bourgogne University, Dijon, France.
Anne
A
Tromelin
Centre des Sciences du Goût et de l'Alimentation, UMR6265 CNRS, UMR1324 INRA, Bourgogne University, Dijon, France.
Anne Marie
AM
Le Bon
Centre des Sciences du Goût et de l'Alimentation, UMR6265 CNRS, UMR1324 INRA, Bourgogne University, Dijon, France.
Christine
C
Belloir
Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Rasmus Koefoed
RK
Petersen
Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Karsten
K
Kristiansen
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
Søren
S
Brunak
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark; INSERM UMR-S973, Molecules Thérapeutiques In Silico, Paris Diderot University, Paris, France.
Olivier
O
Taboureau
D002874:Chromosome Mapping / Q000379:methods*; D015894:Genome, Human / Q000502:physiology*; D006801:Humans; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism; D018035:Receptors, Odorant / Q000235:genetics* / Q000378:metabolism
D047495:PPAR gamma; D043884:Receptor, Cannabinoid, CB1; D018035:Receptors, Odorant