Tubulin as a smart material and a flexible drug target
Event details
| Date | 11.05.2026 |
| Hour | 12:15 › 13:15 |
| Speaker | Prof. Nikita Gudimchuk, Faculty of Physics, Lomonosov Moscow State University |
| Location | Online |
| Category | Conferences - Seminars |
| Event Language | English |
WEEKLY EPFL BIOE TALKS SERIES (sandwiches provided)
Abstract:
Microtubules are dynamic protein filaments that play central roles in cell organization, transport, and division. Their ability to rapidly assemble, disassemble, and generate forces allows cells to continuously adapt their internal architecture to changing conditions, enabling processes such as migration, polarization, and mitosis.
In the first part of my talk, I will discuss the mechanisms governing the emergence of these complex behaviors from the physical properties of tubulin, the molecular building block of microtubules. At least two key features make tubulin a non-trivial material with ‘smart’ mechanical properties. First, tubulin dimers are highly allosteric, and their conformation depends on their biochemical state: the GTP-bound state promotes microtubule assembly, whereas transition to the GDP-bound state through GTP hydrolysis destabilizes the lattice and triggers microtubule depolymerization. Second, even in the assembly-competent GTP-bound state, tubulin dimers are incorporated into the microtubule lattice in a deformed, strained conformation. As a result, microtubule assembly stores elastic energy and creates a metastable, pre-stressed polymer capable of releasing this energy to generate mechanical force. De novo assembly (nucleation) of microtubules proceeds through a series of metastable intermediates that progressively straighten while accumulating more and more mechanical strain. The energetic cost of tubulin deformation introduces kinetic barriers along both nucleation and elongation pathways, providing opportunities for regulatory proteins to modulate microtubule assembly by tuning these energy barriers. In this way, cells gain a versatile toolkit to regulate and adapt the microtubule cytoskeleton to a wide range of functions.
In the second part of the talk, I will discuss tubulin as a long-standing and still highly relevant drug target. While classical microtubule-targeting agents are widely used in cancer therapy as cytostatics, emerging tools now enable systematic exploration of tubulin–ligand interactions in new ways. In our laboratory, we have developed a versatile fluorescent probe that enables the identification of unconventional tubulin-binding compounds. This approach may facilitate the development of modulators of the microtubule cytoskeleton that more selectively adjust cellular processes by blocking or enhancing interactions between microtubules and associated proteins, rather than interfering with assembly/disassembly dynamics.
Bio:
Nikita Gudimchuk graduated from the Faculty of Physics at Lomonosov Moscow State University in 2009. He carried out research at the University of Colorado Boulder (2008–2010) with J.R. McIntosh, studying kinetochore–microtubule interactions using optical trapping and fluorescence microscopy. He then worked as a visiting scholar at the University of Pennsylvania (2010–2013) with E.L. Grishchuk and Fazly Ataullakhanov, focusing on single-molecule studies of kinetochore motor proteins and microtubule dynamics, and contributing to the development of advanced optical tweezers instrumentation. He received his PhD in Biophysics in 2013.
In 2013, he returned to Moscow State University, where he continued his research with Fazly Ataullakhanov. Since 2019, he has led the Laboratory of Cytoskeleton Biophysics at the Center for Theoretical Problems of Physicochemical Pharmacology of the Russian Academy of Sciences. He is also a group leader and Deputy Chair of the Biophysics Department at the Faculty of Physics, Lomonosov Moscow State University.
Nikita Gudimchuk obtained his Doctor of Science (Habilitation) degree in 2022, with a thesis focused on the mechanisms of microtubule dynamics and chromosome transport during mitosis. His research combines quantitative experiments and computational modeling to study cytoskeletal systems and cell division. He has received several national awards for young scientists and has been supported by grants from the Russian Science Foundation and the Russian Foundation for Basic Research. He currently teaches courses in cell biophysics and computational modeling in biology at the Faculty of Physics, Lomonosov Moscow State University.
Zoom link (with one-time registration for the whole series) for attending remotely: https://go.epfl.ch/EPFLBioETalks
Instructions for 1st-year Ph.D. students planning to attend this talk, who are under EDBB’s mandatory seminar attendance rule:
IN CASE you cannot attend in-person in the room, please make sure to
Abstract:
Microtubules are dynamic protein filaments that play central roles in cell organization, transport, and division. Their ability to rapidly assemble, disassemble, and generate forces allows cells to continuously adapt their internal architecture to changing conditions, enabling processes such as migration, polarization, and mitosis.
In the first part of my talk, I will discuss the mechanisms governing the emergence of these complex behaviors from the physical properties of tubulin, the molecular building block of microtubules. At least two key features make tubulin a non-trivial material with ‘smart’ mechanical properties. First, tubulin dimers are highly allosteric, and their conformation depends on their biochemical state: the GTP-bound state promotes microtubule assembly, whereas transition to the GDP-bound state through GTP hydrolysis destabilizes the lattice and triggers microtubule depolymerization. Second, even in the assembly-competent GTP-bound state, tubulin dimers are incorporated into the microtubule lattice in a deformed, strained conformation. As a result, microtubule assembly stores elastic energy and creates a metastable, pre-stressed polymer capable of releasing this energy to generate mechanical force. De novo assembly (nucleation) of microtubules proceeds through a series of metastable intermediates that progressively straighten while accumulating more and more mechanical strain. The energetic cost of tubulin deformation introduces kinetic barriers along both nucleation and elongation pathways, providing opportunities for regulatory proteins to modulate microtubule assembly by tuning these energy barriers. In this way, cells gain a versatile toolkit to regulate and adapt the microtubule cytoskeleton to a wide range of functions.
In the second part of the talk, I will discuss tubulin as a long-standing and still highly relevant drug target. While classical microtubule-targeting agents are widely used in cancer therapy as cytostatics, emerging tools now enable systematic exploration of tubulin–ligand interactions in new ways. In our laboratory, we have developed a versatile fluorescent probe that enables the identification of unconventional tubulin-binding compounds. This approach may facilitate the development of modulators of the microtubule cytoskeleton that more selectively adjust cellular processes by blocking or enhancing interactions between microtubules and associated proteins, rather than interfering with assembly/disassembly dynamics.
Bio:
Nikita Gudimchuk graduated from the Faculty of Physics at Lomonosov Moscow State University in 2009. He carried out research at the University of Colorado Boulder (2008–2010) with J.R. McIntosh, studying kinetochore–microtubule interactions using optical trapping and fluorescence microscopy. He then worked as a visiting scholar at the University of Pennsylvania (2010–2013) with E.L. Grishchuk and Fazly Ataullakhanov, focusing on single-molecule studies of kinetochore motor proteins and microtubule dynamics, and contributing to the development of advanced optical tweezers instrumentation. He received his PhD in Biophysics in 2013.
In 2013, he returned to Moscow State University, where he continued his research with Fazly Ataullakhanov. Since 2019, he has led the Laboratory of Cytoskeleton Biophysics at the Center for Theoretical Problems of Physicochemical Pharmacology of the Russian Academy of Sciences. He is also a group leader and Deputy Chair of the Biophysics Department at the Faculty of Physics, Lomonosov Moscow State University.
Nikita Gudimchuk obtained his Doctor of Science (Habilitation) degree in 2022, with a thesis focused on the mechanisms of microtubule dynamics and chromosome transport during mitosis. His research combines quantitative experiments and computational modeling to study cytoskeletal systems and cell division. He has received several national awards for young scientists and has been supported by grants from the Russian Science Foundation and the Russian Foundation for Basic Research. He currently teaches courses in cell biophysics and computational modeling in biology at the Faculty of Physics, Lomonosov Moscow State University.
Zoom link (with one-time registration for the whole series) for attending remotely: https://go.epfl.ch/EPFLBioETalks
Instructions for 1st-year Ph.D. students planning to attend this talk, who are under EDBB’s mandatory seminar attendance rule:
IN CASE you cannot attend in-person in the room, please make sure to
- send Fiorella Ghisays a note well ahead of time (ideally before seminar day), informing that you plan to attend the talk online, and, during seminar:
- be signed in on Zoom with a recognizable user name (not any alias making it difficult or impossible to identify you).
Practical information
- Informed public
- Registration required
Organizer
- Prof. Georg Fantner, Institute of Bioengineering
Contact
- Fiorella Ghisays, Institute of Bioengineering (IBI)