Computational Receptor Biology – Gloriam Group

David Gloriam’s group identifies mechanisms, structures and ligands of G protein-coupled receptors (GPCRs) – the main mediators of human signalling and drug responses – and develop the field’s main online database, GPCRdb (see video and GPCRdb.org).

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

GPCR activation mechanisms across classes and macro/microscales
Nature Structural & Molecular Biology. Accepted

GPCRdb in 2021: Integrating GPCR sequence, structure and function
Nucleic Acids Research. 2021

Discovery of Human Signaling Systems: Pairing Peptides to G Protein-Coupled Receptors.
Cell. 2019

An online resource for GPCR structure determination and analysis.
Nature Methods. 2019

Trends in GPCR drug discovery: new agents, targets and indications
Nature Reviews Drug Discovery. 2017 [Citations: 1,065]

From collaborations
Structural insights into the lipid and ligand regulation of serotonin receptors
Nature. 2021

Structure of the class D GPCR Ste2 dimer coupled to two G proteins.
Nature. 2020

Combinatorial expression of functionally distinct GPCR isoforms can diversify receptor signalling
Nature. 2020

Pharmacogenomics of GPCR drug targets
Cell. 2018 [Citations: 329]

Selectivity determinants of GPCR–G-protein binding
T Flock, AS Hauser, N Lund, DE Gloriam, S Balaji, MM Babu
Nature. 2017 [Citations: 217]

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Albert J. Kooistra receives the MGMS Frank Blaney Award

2021.11.27

portrait Albert Kooistra

David Gloriam receives big data prize from the Danish Royal Academy of Sciences and Letters

2021.10.08

portrait

Alexander S. Hauser receives Bachem Award for Peptide Science

2021.03.26

portrait of award winner Alexander Hauser

Alexander Hauser receives HC Ørsted research talent prize

2019.08.14

portrait Alexander Hauser

Professor inauguration

09.05.2019
Inauguration of David Gloriam as Professor. … »

David Gloriam at a reception

Crystal refinement bronze

15.11.2016
Bronze prize in crystal structure refinement.
Louise Nikolajsen got bronze prize (diploma and money) in a GPCR crystal refinement competition at the 4th Annual Shanghai iHuman Forum.

Portrait of Louise Nikolajsen holding her diploma

Wikipedia gold

11.07.2016
Gold prize in Wikipedia competition. 
The International Society for Computational Biology (ISCB) announces competitions to improve the coverage on Wikipedia of any aspect of computational biology. In the last WikiProject competition PhD student Alexander S. Hauser has been awarded 1st and 2nd prize awards with an in-depth update of the molecular docking Wikipedia page as well as Wikidata entry. 

Portrait of Alexander Hauser

Oral & poster awards

01.06.2016
2nd Central European Biomedical Congress. 
Stefan Mordalski and Gáspár Pándy-Szekeres received awards for their oral and poster presentations, respectively, at the 2nd Central European Biomedical Congress, in Krakow, Poland.

group portrait of Stefan Mordalski and Gáspár Pándy-Szekeres

GPCR modelling gold

01.08.2014
Best 5-HT1B model in global competition. 
1st and 3rd places in the GPCR  Dock competition for structure modeling of the serotonin 5-HT1B receptor and receptor-ligand complex, respectively. GPCR Dock is a highly competitive competition and involved 44 international groups, including leading GPCR modelers and software developers.

 

 

 

 

 

 

 

 

GPCRdb accelerates data-driven receptor research

2021 01 18
GPCRdb accelerates data-driven receptor research

Discovery of new hormone-receptor signalling systems

2019.10.31
Press release and video

Ultra-large virtual screening for drugs

2019.02.06
News & views article and podcast

Press release: GPCR structure determination resource

2019.01.23
Online tools to determine GPCR 3D structures.
The first web-based tool to determine GPCR 3D structures (Nature Methods) - Eng

Press release: 5-HT2C structure

2018.02.01
Shedding insight on GPCR-ligand polypharmacology.
Polypharmacology and 3D structure of the serotonin 5-HT2C receptor (Cell) - Eng 

Video on GPCR pharmacogenomics

2018.01.11
From the Cell article on pharmacogenomics of GPCR drug targets. … »

Press release: GPCR pharmacogenomics

2017.12.15
Genetic variation in GPCR drug targets.
Pharmacogenomics of GPCR drug targets (Cell) - Eng1Eng2 & Dan 

Press release: GPCR drug discovery

2017.10.31
Trends for drugs, clinical trials and indications.
Trends in GPCR drug discovery (Nat Rev Drug Discov) - Eng & Dan 

Press release: G protein selectivity

2017.05.11
Determinants of GPCR-G protein coupling.
Receptor signalling: GPCR - G protein selectivity (Nature) - Eng & Dan 

Intro to the GPCRdb database

2015.06.01
Popular scientific article about the GPCRdb database.  

Video on orphan receptor ligand identification

2015.01.01
Video made in relation to the award of the Lundbeck Foundation Fellowship to David Gloriam. English: … »

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Research

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

The individual phenotypic and molecular response to a given therapeutic treatment is a convoluted trail, shaped by inherited and environmental factors. The genetic variation across individuals leads to personal differences in the metabolism, therapeutic effects and adverse reactions of drugs. Pharmacogenomics aims to target treatments by considering each individual’s genetic makeup. The main goal of personalised medicine is to tailor drug prescriptions to individuals to achieve the most effective and least harmful treatment. This is important to quicker find the optimal of multiple drugs and to avoid unnecessarily high dosages.

Key to realising the potential of personalised medicine is integrating systems biology, statistics and bioinformatics to associate genotypes to phenotypes. Our work bridges the fields of genetics and genomics, structural biology, pharmacology, drug development and medicine, as a case study for GPCRs. This is very timely considering the novel big datasets which combined with high-throughput pharmacology and the unique Danish registries provide an innovative new approach to advance personalised medicine.

On this foundation, we have started a new project titled Advancing personalised medicine for psychiatric diseases through integrative GPCR Pharmacogenomics, funded by the Lundbeck Foundation (~10 million DKK). The project is headed by Hans Bräuner-Osborne and the computational data science analyses are driven by Alexander Hauser within the Gloriam group. The project is run in collaboration with iPSYCH collaborators Preben Bo Mortensen (National Centre for Register-based Research) and Thomas Werge (Institute of Biological Psychiatry).

The project spans four specific aims:
1. Predict GPCR mutations affecting CNS drug response (in silico)
2. Determine how psychiatric drug responses are affected by genetic variations (in vitro)
3. Delineate genetic variants associated with disease or a change of clinical therapy (in human)
4. Create a public platform to phenotype GPCR variants for personalised medicine (in field)

Our linking of missense variants to patient disease cohorts will be very valuable for: (i) more accurate patient sub-diagnoses for genotype-based personalised treatment, (ii) patient stratification upon entering clinical trials, and (iii) increased precision in delineation of changes in clinical therapy, (iv) personalise medicine prescriptions based on GPCR genotypes, (v) prioritise drugs for pharmacovigilance investigations, and (vi) design post-market follow-up studies e.g. drug repurposing.

 

 

 

 

 

 

 

 

 

 

 

 

 

Group leader

Group Leader

David Gloriam
 Professor

Phone +45 3533 6162
david.gloriam@sund.ku.dk

Group members

Name Title Image
Caroli, Jimmy Postdoc Billede af Caroli, Jimmy
Harpsøe, Kasper Research Consultant Billede af Harpsøe, Kasper
Hauser, Alexander Sebastian Associate Professor Billede af Hauser, Alexander Sebastian
Kastrup, Jette Sandholm Jensen Professor Billede af Kastrup, Jette Sandholm Jensen
Kooistra, Albert Jelke Associate Professor Billede af Kooistra, Albert Jelke
Kulkarni, Yashraj Postdoc Billede af Kulkarni, Yashraj
Pedersen, Eva-Marie Lucin Mokdasi A Laboratory Technician Billede af Pedersen, Eva-Marie Lucin Mokdasi A
Pándy-Szekeres, Gáspár Academic Research Staff Billede af Pándy-Szekeres, Gáspár
Schaller, Kay Postdoc Billede af Schaller, Kay
Simonyan, Arman Research Assistant Billede af Simonyan, Arman