Research
Overview
Microtubules are cytoskeletal polymers of tubulin, which intermittently assemble and disassemble in all known eukaryotic cells. Functions of these filaments include intracellular transport, organization of the intracellular space, segregation of chromosomes and other. We use computational, biochemical and biophysical approaches to understand the mechanisms underlying microtubule dynamics and their interplay with various cellular processes in norm and pathology.
Ongoing projects include:
1. Multi-scale modeling and in vitro reconstitutions of microtubule dynamics and mechanics
Using a combination of optical microscopy, electron cryotomograpy and computational modeling we thrive to find out:
1) how microtubules assemble and dissasemble?
2) how they transition between these dynamic phases?
3) how they use energy to develop mechanical forces and move intracellular cargoes?
Microtubules are cytoskeletal polymers of tubulin, which intermittently assemble and disassemble in all known eukaryotic cells. Functions of these filaments include intracellular transport, organization of the intracellular space, segregation of chromosomes and other. We use computational, biochemical and biophysical approaches to understand the mechanisms underlying microtubule dynamics and their interplay with various cellular processes in norm and pathology.
Ongoing projects include:
1. Multi-scale modeling and in vitro reconstitutions of microtubule dynamics and mechanics
Using a combination of optical microscopy, electron cryotomograpy and computational modeling we thrive to find out:
1) how microtubules assemble and dissasemble?
2) how they transition between these dynamic phases?
3) how they use energy to develop mechanical forces and move intracellular cargoes?
2. Investigation of microtubule interactions with kinetochore and microtubule associated proteins
We study how microtubule behavior is regulated in cells by associated proteins, and how proteins couple microtubule dynamics to chromosome motions. Some of our favorite questions include:
1) How does the key kinetochore complexes, NDC80 and Dam1 (in yeast) function at the molecular level?
2) How do the most faithful partners of tubulin, the end-binding (EB) proteins, recognize growing microtubule tips and modulate microtubule dynamics?
3) How do other microtubule regulators, such as TOG-contaning polymerases, kinesin and stathmin depolymerases and severing enzymes catalyze changes in microtubule behavior?
We study how microtubule behavior is regulated in cells by associated proteins, and how proteins couple microtubule dynamics to chromosome motions. Some of our favorite questions include:
1) How does the key kinetochore complexes, NDC80 and Dam1 (in yeast) function at the molecular level?
2) How do the most faithful partners of tubulin, the end-binding (EB) proteins, recognize growing microtubule tips and modulate microtubule dynamics?
3) How do other microtubule regulators, such as TOG-contaning polymerases, kinesin and stathmin depolymerases and severing enzymes catalyze changes in microtubule behavior?
3. Development of new anti-cancer drugs, targeting tubulin and microtubule associated proteins
1) We use our multi-scale computational modeling approach to establish the mechanisms of action of clinically proven and new anti-tubulin drugs
2) Through molecular docking, molecular dynamics, TIRF microscopy and other biophysical and biochemical techniques we search for new small-molecule drugs targeting tubulin, important kinetochore proteins and microtubule regulators.
1) We use our multi-scale computational modeling approach to establish the mechanisms of action of clinically proven and new anti-tubulin drugs
2) Through molecular docking, molecular dynamics, TIRF microscopy and other biophysical and biochemical techniques we search for new small-molecule drugs targeting tubulin, important kinetochore proteins and microtubule regulators.
