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Dr.Rosie Dawaliby - Development of conformational and environmental sensitive therapeutics and diagnostic tools using pathology-like in vitro stabilized membrane proteins (MP) targets

 

Rosie Dawaliby

G CLIPS BIOTECH, Toulouse

Development of conformational and environmental sensitive therapeutics and diagnostic tools using pathology-like in vitro stabilized membrane proteins (MP) targets

A major bottle neck in drug discovery targeting transmembrane proteins (MP), is to reproduce their native conformation and microenvironment in vitro. G.CLIPS enabling  technology is a game changer aimed at controlling the lipidic environment and conformation of MP drug targets. Indeed, G.CLIPS is specialized in the stabilization of isolated MP in specific conformations and/or lipid environments. Our aim is to further develop this innovative technology in the discovery of novel conformational and environmental sensitive vaccines, antibodies or small molecule drugs targeting MP. In this work, we focus on a model G protein coupled receptor (GPCR) and we show that our technology allows:

1) structural and conformational stabilization of purified model G protein coupled receptor (GPCR),

2) embedding of the GPCR in tissue-like nanodiscs and monitoring its effect on the receptor activation state,

3) differential pharmacological profiling of benchmark ligands on the receptor stabilized in different conformation/environments.

 

Selected references

  • Dawaliby R, Trubbia C, Delporte C et al. Allosteric regulation of GPCR activity by phospholipids. Nat Chem Biol 2016 12(1):35–39​​​​​​
  • Martens C, Stein RA, Masureel M et al. Lipids modulate the conformational dynamics of a secondary multidrug transporter. Nat Struct Mol Biol 2016 23(8):744–751
  • Dawaliby R, Trubbia C, Delporte C et al. Phosphatidylethanolamine is a key regulator of membrane fluidity in eukaryotic cells. J Biol Chem 2016 291(7):3658–3667

Contact: Olivier Neyrolles (Olivier.Neyrolles@ipbs.fr)

Link to attend the seminar:

13 Sep

11:00 - 12:00

Seminar room - IPBS | Hybrid conference