Ziel
Actin cytoskeleton dynamics is the fundamental principle underlying diverse cellular processes such as muscle contraction, embryonic development and wound healing.
Our long-term goals are
- to understand how dynamic stability of the actin cytoskeleton is maintained,
- how actin-based machineries control cell functions such as podosome formation and phagocytosis and
- what role actin-dependent processes play in pathological situations such as tumour metastasis and vascular injury.
Our research aims at understanding factors which associate directly with the actin filament and which are responsible for the modulation and stabilization of actin assemblies at the molecular and cellular level. One such factor, the actin-binding protein calponin (CaP) has been identified in a 17-gene signature profile of metastasising tumours.
We will investigate the molecular basis for the function of CaP in this profile, and establish the potential correlation between reduced CaP levels, the formation of podosomes and the induction of metastasis. Actin cytoskeleton remodelling during receptor-mediated phagocytosis provides the structural basis for the engulfment of particles.
We plan to characterise the composition of the multi-molecular complex(es) involved, and to analyse the functions of individual components, particularly focusing on the interactions of the adaptor protein Fyb/SLAP and of its domains.
Protein linguistics predicts that compositional semantics work in biological systems, as much as they do in human languages. We plan to address the conceptual problem underlying the evolution of functional diversity in cytoskeletal proteins, focusing on molecules regulating actin structure, stability and dynamics.
Employing the calponin-homology domain as a model tool, we will investigate the effects of compositional variation, positional modulation and the replacement and mutation of regulatory loops, in order to understand how these parameters dictate functional plasticity.
Wissenschaftliches Gebiet
Thema/Themen
Aufforderung zur Vorschlagseinreichung
FP6-2002-MOBILITY-8
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