Date : 02/10/2011

Internship proposal for : Master 1 or Master 2

Laboratory
Laboratoire de Biologie Physico-Chimique des Protéines Membranaires
UMR 7099 CNRS U. Paris Descartes
13 rue Pierre et Marie Curie 75005 Paris
Website : www.ipbc.fr
Main discipline : Biophysics
Lab director : Bruno Miroux

Mentor
Valérie Biou
email : Cet e-mail est protégé contre les robots collecteurs de mails, votre navigateur doit accepter le Javascript pour le voir
tel +33 1 69 82 34 81

Subjects
1.: signaling pathway
2.: structural biology
3.: cancer

Tools and methodologies
1.: X-ray crystallography
2.: biophysics
3.: enzyme kinetics

Summary of lab's interests

Our laboratory gathers biologists, physicists and chemists who are interested in the structure, structural dynamics and physical chemistry of membrane proteins, either in vivo within a lipid bilayer, or in vitro after solubilization and stabilization by classical or alternative surfactants such as amphipols. Our proteins of interest cover various domains of fundamental and medical biology: the bioenergetic of chloroplasts and mitochondria, with the structure-function study of the cytochrome b6f complex and the mitochondrial uncoupling proteins. ion channels, with the solid state NMR study of the bacterian mechanosensitive ion channel MscL. signal transduction in the G protein-coupled receptors family and associated proteins, with the NMR study of the eicosanoid receptor and structural approach of the Hedgehog signaling pathway.

Summary of project

background: The Hedgehog signalling pathway controls stem cell differentiation during embryogenesis. The neural tube and many organs such as the lungs depend on the pathway for their correct genesis. Disregulation leads to genetic diseases such as holoprosencepaly in infants, and is related to many cancers in adults. The hedgehog pathway is regulated by a signal transduction protein complex in which protein-protein interactions are modulated by alternating phosphorylations. Although numerous studies have been published on the cellular and organ aspect of the Hedgehog pathway and particularly its relationship to cancer, the protein-protein interactions have not been described at a structural level. In our laboratory, we undertook to study the structure of the Hedgehog signalling complex, in an environment involving biochemists, biophysicists and X-ray crystallographers. In addition, we have collaborations with several teams of biologists working on the Hedgehog pathway. Internship work: We characterise the structure, enzyme properties and phophorylation sites of the Hedgehog protein complex members. Several proteins have already been expressed and characterised. During his or her internship, the student will 1) determine conditions in which two of the proteins can form a complex; 2) measure the stoichiometry; 3) crystallise the complex. This internship combines structural biology, biophysics and biochemistry into a high level training concerning a highly important biomedical subject. It can lead to a thesis during which the different steps will be pursued and extended to other proteins of the complex.