Vladimir Varga Group

Eukaryotic cilia and flagella are evolutionary well-conserved organelles with critical functions in cell motility, sensing and signalling. Malfunctions of these organelles cause pleiotropic diseases called ciliopathies. Our laboratory addresses the question of how does the very complex yet highly organized cytoskeleton of these organelles form.

To answer this we study the protozoan parasite Trypanosoma brucei, the causative agent of sleeping sickness, which is an experimentally highly tractable flagellated organism. This facilitates development of novel biochemistry, molecular biology, and cell biology approaches, enabling description of key processes and identification of proteins involved. This is important as the flagellum is critical for the parasite survival in its host.

Moreover, leveraging the high evolutionary conservation of the organelles we study mammalian orthologs of the identified trypanosome proteins. We investigate their roles in mammalian motile and primary cilia using tissue cultures as well as animal models. This approach contributes to our understanding of these fascinating organelles and has a potential to reveal causes of certain types of ciliopathies.

FUTURE PROJECTS

We will continue using the evolutionary approach to discover proteins critical for construction and function of the flagellar and ciliary cytoskeleton. We further continue developing biochemistry and imaging methods to achieve better understanding of these processes with the ultimate aim to reconstitute some of the key processes in in vitro biochemical assays. By employing this comprehensive approach we willgain a mechanistic understanding of the flagellar and ciliary cytoskeleton.

METHODOLOGICAL AND TECHNICAL EXPERTISE

Molecular and cell biology experiments with trypanosomes and mammalian cell cultures

Live cell imaging of processes occurring in flagella and cilia

In vitro reconstitution assays