|
|
|
Research
interests
Microtubules are intracellular dynamic polymers made up of evolutionarily
conserved polymorphic alpha/beta-tubulin heterodimers and a large number of
microtubule-associated proteins. Microtubules are required for vital processes
in eukaryotic cells including mitosis, meiosis, maintenance of cell shape and
many forms of intracellular transport. Various signaling molecules interact with
microtubule components, and microtubules are likely to be the critical factors
for spatial organization of signal transduction. Several populations of
microtubules of different composition, stability and properties carry out these
essential functions in cells. Posttranslational modifications of tubulins play
an important role in the determination of microtubule properties. Organization
of microtubular networks in cells is controlled by microtubule organizing
centres (MTOCs). One of the key components of MTOCs is the gamma-tubulin which
is necessary for nucleation and organization of microtubules. Gamma-tubulin also
exists in cells in the form of soluble gamma-tubulin complexes, whose functions
are just about beginning to be understood. In addition, gamma tubulin may
participate in other cell functions, such as cell cycle progression or dynamics
of the microtubule ends.
The long-term research program of
the laboratory of Dr. Pavel Draber includes the study of structure-function
relationships of microtubule proteins and their interactions with other
cytoskeletal elements in cells under normal and pathological conditions. To this
end the research group has used immunological approaches and prepared a panel of
monoclonal antibodies that made it possible to contribute to the structural
mapping of tubulin dimers, to analyse their posttranslational modifications and
to identify the microtubule-interacting proteins. Recently the research efforts
concentrated towards the elucidation of the molecular mechanisms governing the
microtubule nucleation and the role of gamma-tubulin in this process. It has
been shown that soluble gamma-tubulin is posttranslationally modified, interacts
with tubulin heterodimers and forms complexes with protein tyrosine kinase.
Experimental evidence has been provided that the properties of gamma-tubulin
change during differentiation events, and that gamma-tubulin is not universal
nucleator of microtubules. It could also be demonstrated that gamma-tubulin in
plant cells is located in the kinetochore/centromeric region of chromosomes
under normal conditions and is present in membrane-associated complexes.
Current work focuses on 1) the
understanding of the function of gamma-tubulin forms in different cell types, 2)
modulation of microtubule properties by signal transduction molecules, and 3)
molecular and functional characterisation of components of MTOCs. To address
these questions, techniques of molecular biology, biochemistry and immunology
are being used, as well as a variety of microscopic techniques.
|
|
