Thomas Antoine

Name

Name: Thomas ANTOINE

Nationality: French

Intana Bioscience GmbH
Lochhamer Str. 29a
D-82152 Planegg/Martinsried 4)

Contact details:
E-mail: thomas.antoine@intana.de
Phone: +49 (0)89 89 55 72 80

Biosketch

Thomas Antoine graduated from the Ecole Supérieure d’Ingénieurs de Luminy (ESIL, Marseille, France) with a M.Sc. in Biotechnology in autumn 2008. He carried out his master thesis in the X-ray crystallography department of Sanofi Aventis (Strasbourg, France) during 6 months. In 2009, Thomas integrated the “InterMalTraining” PhD program (Intervention strategies against malaria) and was granted with an EU FP7 Marie Curie fellowship to pursue a PhD at the department of Parasitology of the Liverpool School of Tropical Medicine (Liverpool, United Kingdom). Under the supervision of Prof. Steve Ward, he worked on the electron transport chain of the malaria parasite mitochondrion and obtained his degree in 2012. Thomas joined Intana Bioscience GmbH (Munich, Germany) as a Marie Curie postdoctoral fellow in October 2012 where his current interest is to develop a FCCS platform to investigate drug-membrane proteins interactions.

Project title: Enabling FCCS-based affinity measurements of membrane-drug interactions

Project summary:

A large variety of drugs interfere with sphingolipid homeostasis, but their mechanisms of action are often poorly understood. Additionally, basic research has led to the identification of many potential drug targets in various disease areas, that relate to sphingolipids and sphingolipid homeostasis but translation of this knowledge into novel therapeutic agents by the pharmaceutical industry is hampered by difficulties in developing assays for many of those targets. In particular a plethora of membrane proteins defy standard biochemical assays, which are critical tools to develop potent and selective drugs. FCCS (Fluorescence Cross Correlation Spectroscopy) has been employed as generically applicable tool to characterize biomolecular interactions with respect to affinity and binding kinetics. In particular, FCCS was successfully used to test drug target interactions in crude cellular lysates and living cells, thereby providing a physiological environment. However, to this point the usage of FCCS was restricted to soluble proteins and ligands.

In this project, FCCS will be employed to characterize interactions of membrane proteins to their natural ligands and potential inhibitors in living cells, cellular lysates and purified protein fractions. Our approach is focused on membrane proteins having high potential for future pharmaceutical development such as receptor tyrosin kinases (RTKs), SMS-related proteins (SMSr), G-protein coupled receptors (GPCRs) some of which are involved in sphingolipid homeostasis. FCCS measurements require monodisperse solubilised and fluorescently labelled molecules. One of the main challenges is to solubilise membrane proteins and preserve functionality. For this we would like to establish model membrane systems enabling FCCS (Fluorescence Cross Correlation Spectroscopy) measurements without affecting the functionality of embedded membrane proteins. The nanodisc technology is an emerging artificial membrane system for the study of membrane proteins. Being more stable and monodisperse than conventional model membranes such as liposomes, bicelles or micelles, the nanodisc is an excellent alternative for single-molecule fluorescence applications.

Supervisors

Stefan Hannus (Intana Bioscience GmbH, Munich, Germany)
Christian Heinis (EPFL, Lausanne, Switzerland)

Biosketch 1st scientific supervisor:

Dr. Stefan Hannus studied Biology at the University Regensburg with focus on molecular biology and biochemistry. Before starting his PhD thesis, he joined the Lab of Prof. Dr. E. Hurt in Heidelberg investigating ribosomal transport across the nuclear pore complex. He received his predoctoral education at the EMBL in Heidelberg and the Max-Planck-Institute for Biochemistry in Martinsried conducting research on the biogenesis of ribonuclear protein complexes. In 2001 Stefan Hannus started as scientist at GPC Biotech AG where he developed and established FCCS as tool to study compound target interactions. In 2008 he founded jointly with Dr. Frank Becker Intana Bioscience GmbH.