Investigation of Drug-Target interactions using FCCS


Project description
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 pharma 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.

Further reading
1) Glauner, Ruttekolk, Hansen, Steemers, Chung, Becker, Hannus, Brock, Simultaneous detection of intracellular target and off-target binding of small molecule cancer drugs at nanomolar concentrations, British Journal of Pharmacology, 160, 958-70, 2010.
2) Hansen, Ruttekolk, Glauner, Becker, Brock, Hannus, The in vitro biological activity of the HLA-DR-binding clinical IgG4 antibody 1D09C3 is a consequence of the disruption of cell aggregates and can be abrogated by Fab arm exchange, Molecular Immunology, 46, 3269-77, 2009.

Host institute
Intana Bioscience GmbH
Lochhamerstrasse 29A
82152 Martinsried
Supervisor: Dr. Stefan Hannus

Intana Bioscience GmbH was founded in 2008 and is a small privately owned enterprise, located in Martinsried, (Germany) with currently 8 employees.  Intana offers interaction analysis based on single molecule sensitive spectroscopic approach called fluorescence cross correlation spectroscopy (FCCS).

•    We are looking for a highly committed and independent PhD with strong background in biochemistry of membrane proteins and/or Correlation Spectroscopy. Additionally, experience in drug screening and assay development would be beneficial.
•    The successful candidate will be part of a young start up company. The technology spectrum covers molecular biology, biochemistry, cell biology, spectroscopy and imaging
•    Proactive participation in SPHINGONET’s research & training program is expected through presentations and critical thinking at internal scientific forums, requiring excellent English presentation and writing skills. Strong communication skills and the ability to work in a team are a must.
•    Candidates must fulfill the eligibility criteria for Marie Curie Initial Training Networks (FP7).
•    Candidates should submit the complete application package.
•    Suitable candidates will be invited for an interview by the supervisor of the project.

•    Post Doc for 2 years.
•    Full-time (42 hours/week).