Research Projects (Third party funds)
Molecular Mechanisms of Cell Motility
The central topic of the Research Unit is the interplay between molecular motors, the components of cell adhesion complexes, and the actin- and microtubule-based cytoskeleton. This complex interplay and its modulation by chemical and mechanical signals plays a key role in defining cell shape, motility, adhesion, and polarity. During embryogenesis, it is important for the organisation of three-dimensional cellular assemblies leading to the formation of tissues and organs. Increased motility contributes to invasion and metastasis of tumour cells. In recent years, considerable progress has been made in identifying the key players that drive a wide range of motile events and important details about the underlying molecular mechanisms have been revealed. However, information about the way in which actin filaments interact with microtubules and microtubules with focal adhesions is still scarce.
While the details of the molecular mechanisms leading to the formation of cell surface extensions involving polarised actin-rich structures are beginning to emerge, it remains unclear why under certain conditions filopodia, lamellopodia or membrane ruffles are formed. It is crucial to understand the mechanical and biochemical signals that instruct the cytoskeleton to form a certain type of extension as the dynamic behaviour of polarised actin-rich structures is also responsible for the formation of specialised cell surface structures such as microvilli and stereocilia bundles.
A better understanding of the molecular mechanisms of cell locomotion will contribute to our understanding of these physiological and pathological processes. We will work towards this goal using a multifaceted approach to characterise components of the actin- and microtubule-based cytoskeleton, adhesion complexes, and processive molecular motors. This will include the detailed biochemical and structural analysis of isolated proteins and protein complexes, the use of in vivo and in vitro assays to directly observe protein function, and molecular genetic approaches to selectively deplete proteins of interest or produce them in a recombinant form. Dictyostelium, tissue culture cells and mice will be used as model systems to study the function of proteins of interest. This allows the researchers to take advantage of the powerful molecular genetics, easily accessible phenotypes and strong biochemistry in Dictyostelium and to test the relevance of our findings in the context of more complex systems.