Research

Basic introduction:

Cell-matrix adhesion: an essential contact for tissue morphogenesis

Cell-matrix adhesion: an essential contact for tissue morphogenesis

In multicellular organisms cells form adhesive contacts with other cells and with the extracellular matrix (ECM). The ECM is a meshwork of proteins that surrounds many cell types and serves a variety of functions, such as substrate for stable cell anchorage, a route for cell migration during development and a source of signals to the cells. In all of these processes membrane receptors link the extracellular ligands to the cortical cytoskeleton, enabling a continuous dynamic interaction between cell and ECM. A well-established family of ECM-receptors is the integrin family. The dual role of integrins as adhesion receptors and signal transducers have become one paradigm of how transmembrane proteins function and permit the communication of cells with their environment. In the context of the whole organism, integrins have an essential role in normal development by maintaining tissue integrity. In addition, defects in integrin adhesion cause a number of human pathologies such as muscular dystrophies, immune disorders (e.g. leukocyte adhesion deficiency), blood clotting defects (e.g. Glanzmann thrombasthenia), skin blistering (e.g. epidermolysis bullosa), kidney degeneration, tumor angiogenesis and cancer metastasis.


On-going research projects:

Dissecting the functions of Integrin-Linked Kinase (ILK) and Parvin in Drosophila development
Following adhesion to the ECM, integrins cluster and recruit a large number of cytoplasmic proteins that form a link predominantly to actin cytoskeleton. Recently the term “integrin adhesome” was introduced to describe this molecular assembly of interconnecting proteins. A well established protein complex that links integrins to actin cytoskeleton and regulates the dynamic changes in cell shape is assembled around Integrin-Linked Kinase (ILK) and its binding partner Parvin. Currently my group aims to understand the in vivo functions of the duet ILK-Parvin in Drosophila development and how the “integrin adhesome” is assembled and regulated. We address these questions following a variety of experimental approaches including genetic and biochemical analysis, standard transgenic technologies, and live imaging.

Functions of ILK and Parvin in epithelia morphogenesis
Epithelia morphogenesis largely depends on cell-cell and cell-matrix adhesion. Integrins are localized mainly at the basal side of the cell where primarily link the extracellular matrix (ECM) to the actin cytoskeleton and facilitate transmission of bidirectional signals across the plasma membrane. The combination of the powerfull Drosophila genetic tools, the rather simple epithelium organization and the ability to visualize live dynamic molecular events at the cellular level, make the developing egg chambers of Drosophila an attractive system to investigate the role of ILK and Parvin in the developing epithelia.

Fly egg chambers at various developmental stages	Actin bundles (turquoise) and integrins (yellow) in epithelia cells

Discover novel genes essential for muscle development and function
To delineate further the molecular mechanisms that are implicated in the maintenance of actin cytoskeleton organisation during muscle development, we have performed a candidate loss-of function RNAi screen and identified several essential conserved genes. Currently we are further characterising their expression pattern and in vivo function.

Why functional genetics in Drosophila?
Drosophila is the most well studied multicellular organism which allows the use of sophisticated molecular genetic tools to address basic biological processes in the whole organism in relative short time and in complex genetic background. The molecular function of the majority of proteins is highly conserved between mammals and flies. Therefore targeted functional genomic approaches in Drosophila will improve our understanding and deepen the essential biological knowledge required to design improved drugs and new therapeutic approaches, a great challenge for the biomedical research in the post-genomic era.

Transgenic Drosophila Facility
Our lab houses a transgenic Drosophila facility, in a temperature controlled room equipped with an injection system, inverted microscope and a stereoscope. Over the last years we have generated several transgenic fly models and performed multiple microinjections in embryos for loss of function studies (for more information contact Dr Christos Zervas, czervas@bioacademy.gr or Mrs Katerina Vakaloglou, kvakaloglou@bioacademy.gr).

 

        Our "super"-fly model...