Artem Efremov (Yefremov)

Mechanobiology Institute · National University of Singapore · 5A Engineering Drive 1 · Singapore · 117411 · mbiay@nus.edu.sg

My long-term research interest is to explore the main functioning principles and emergent collective behaviour of such mechanochemical and mechanosensing proteins that underlie molecular processes accountable for the inner organization of living cells and cellular response to environmental cues. In future, this may help to better understand potential roles of this type of proteins in multiple human related diseases, providing new possible directions for their diagnosis and treatment

Research Experience

Senior postdoctoral research fellow

Mechanobiology Institute, National University of Singapore

PI: Prof. Jie Yan.
Project title 1: Application of force-spectroscopy methods for investigation of DNA-binding properties of architectural proteins, and exploration of DNA-protein interactions under applied mechanical constraints.
Project title 2: Role of myosin II motor proteins and formins in filopodia dynamics (independent research in collaboration with Prof. Alexander Bershadsky lab).

February 2013 - Present

Postdoctoral research fellow

Rice University

PI: Assoc. Prof. Michael R. Diehl.
Project title: Studying of molecular motors cooperation in intracellular transportation.

April 2011 - February 2013

Postdoctoral research fellow

National University of Singapore
Singapore-MIT Alliance for Research and Technology (S.M.A.R.T.)

PI: Assoc. Prof. Zhisong Wang and Prof. Jianshu Cao.
Project title 1: Studying of general physical principles underlying the molecular motors' working mechanism.
Project title 2: Investigation of the cytoadhesion properties of malaria infected red blood cells in shear flow.

February 2009 - March 2011

Graduate research assistant

University of Colorado at Boulder
Moscow State University
National Research Center for Hematology, Russian Academy of Medical Sciences

PI: Prof. Fazly I. Ataullakhanov, D.Sc. and Prof. Richard J. McIntosh.
Project title: Investigation of kinetochore-microtubule interactions in higher and lower eukaryotes.

April 2004 - August 2008

Undergraduate research assistant

Moscow State University

PI: Prof. Fazly I. Ataullakhanov, D.Sc.
Project title: Mathematical modeling of microtubule dynamics.

September 2001 - January 2004

Teaching Experience

Project Supervisor

Faculty of Science, National University of Singapore

Managing a computational / theoretical project aimed at establishing of an on-line server that would allow visitors of our web-site to run highly advanced transfer-matrix calculations in order to predict the structure and conformation of DNA interacting with any desirable DNA-binding protein under force and torque constraints applied to the DNA, see detailed description of the project in the attached pdf file. Managed research group working on this project involves one PhD student (Ladislav Hovan) and one Research Assistant (Yang Kaiyuan). Current version of the on-line program can be found via the following web-link: HERE

Number of currently and previously co-supervised graduate students: 6.

2018 - Present

Co-lecturer of Advanced Biophysics course (PC5213) for Master and PhD degree students

Faculty of Science, National University of Singapore

I have been teaching a lecture course, which I have prepared by myself, that describes the major experimental and theoretical biophysical methods widely used in modern single-molecule studies to Master and PhD students starting from early 2016. The course has got many positive feedbacks from students and achieved one of the highest scores among the teaching modules of level 5 (highest university level) taught to Master and PhD students in National University of Singapore, Physics Department, see the attached pdf file containing the detailed module evaluation.

2016 - Present

Education

Moscow State University

Ph.D. in Physics, specialization: Biophysics

Title of the thesis: "Study of microtubules interaction with chromosome kinetochores"

July 2008

Moscow State University and
National Research Centre for Hematology,
Russian Academy of Medical Sciences

Graduate Study, specialization: Biophysics

Title of the thesis: "Investigation of kinetochore-microtubule interactions in higher and lower eukaryotes"

May 2004 - July 2008

Moscow State University

Master of Science Degree in physics (with honor), specialization: Biochemical Physics

Title of the thesis: "Mechanical model of microtubule"

January 2004

Moscow State University

Undergraduate study, specialization: Biophysics

Title of the thesis: "Mathematical modeling of microtubule dynamics"

September 1998 - January 2004

Skills

Programming Languages & Tools
  • Matlab
  • Labview
  • Solidworks
  • Video data processing
  • C++

  • Workflow
    • Molecular Dynamics
    • Modeling of protein dynamics
    • DIC and fluorescent microscopy
    • Cell division (mitosis)
    • Cells immunocytochemistry
    • DNA cloning
    • Mammalian cell culture
    • Biochemical kinetic networks
    • Laser tweezers (optical tweezers, optical trap)
    • Intracellular transport
    • Cells transfection
    • Cells transformation
    • Confocal Microscopy

    Research Interests

    Recently, I have started and been actively working on two independent research projects. Both projects have demonstrated a strong potential in gaining new important insights into the role of intracellular and extracellular mechanical forces in regulation of the chromatin structure as well as in modulation of the dynamics of cell adhesion complexes responsible for the guidance of cell migration, warranting future research in these two directions.


    Project 1: Experimental study of molecular mechanisms involved in regulation of the cell filopodia dynamics and adhesion properties.
    The process of cell migration plays the central role in the development and maintenance of multicellular organisms. Wounds healing, immune response to exogenous pathogens, embryonic tissues formation - these are just a few examples of a large number of vital biological processes that rely on highly ordered collective cell migration, which is required for proper organism functioning.


    Project 2: Development of a general theoretical framework for description of DNA-protein interactions under force and torque constraints.
    The second project is devoted to studying the role of mechanical forces in regulation of DNA-protein interactions, which has been recently suggested to be of large importance in cell-generated response to environmental cues.

    Honors, Awards & Fellowships

    • 2008 - American Society for Cell Biology, Cell Dance 2008 video contest, 2nd place

    • 2005 - Winner of graduate student competition "Moscow Grants 2005" in the nomination "Biology" (from Moscow Government and International Soros Science Education Program)

    • 2004 - Intel award for the second-best student science work at conference "Numerical geometry, grid generation and scientific computing", A.A. Dorodnicyn Computer Center, Russian Academy of Sciences, Moscow, Russia, 28th June - 1st July, 2004

    • 2003-2004 - Moscow Scholarship, Moscow State University

    • 2003-2004 - Vernov Scholarship, Moscow State University

    Downloads

    Programs' source files

    If you use the source code of any of the programs listed below, please, cite the corresponding publications by our research group.
    Matlab programs (written by Artem Efremov):


    • 2016-2017 Matlab bare DNA - the program calculates the physical state of bare DNA (extension, superhelical density and the structural composition) being under force and torque constraints using the transfer-matrix formalism described in [Efremov et al., Phys. Rev. E, 2016] and [Efremov et al., Polymers, 2017]

      The program includes DNA transitions between B-, L-, S- and P-DNA states. The working range: 0 pN <= force <= 200 pN and -30 pN*nm <= torque <= 50 pN*nm. Program inputs: DNA length (nm), force (pN), torque (pN*nm) and the upper boundary on the DNA bending/twisting modes used in the calculations, max_mode. To run the program, type the following command line in Matlab:

      >> main_DNA_force_torque_spectrum_new(DNA_length, force, torque, max_mode)
      For example:
      >> main_DNA_force_torque_spectrum_new(1500, 1, 5, 15)

    • 2017-2018 Matlab DNA-nucleosomes - the program calculates the physical state of DNA interacting with histone octamers that form nucleosomes upon binding to DNA under applied force and torque constraints. The program code is based on the transfer-matrix formalism described in [Efremov and Yan, 2018]

      The program includes DNA transitions between B-, L-, and P-DNA states as well as between B-DNA protein-bound and protein-unbound states. The working range: 0 pN <= force <= 30 pN and -30 pN*nm <= torque <= 50 pN*nm. Program inputs: DNA length (nm), force (pN), torque (pN*nm), the proteins' binding energy (in k_B T units) and the upper boundary on the DNA bending/twisting modes used in the calculations, max_mode. To run the program, type the following command line in Matlab:

      >> main_DNA_nucleosome(DNA_length, force, torque, mu_protein, max_mode)
      For example:
      >> main_DNA_nucleosome(1500, 1, 5, 40, 15)

    • C++ programs (translate from Matlab by Ladislav Hovan):


    • 2018 Feb 21 C++ bare DNA - C++ version of the Matlab program #1 based on the transfer-matrix formalism described in [Efremov et al., Phys. Rev. E, 2016] and [Efremov et al., Polymers, 2017]

      The program working range: 0 pN <= force <= 200 pN and -30 pN*nm <= torque <= 50 pN*nm. Program inputs: DNA length (nm), force (pN), torque (pN*nm) and the upper boundary on the DNA bending/twisting modes used in the calculations, max_mode. To run the compiled program, type the following command line:

      >> Name_of_the_compiled_program DNA_length force torque max_mode
      For example:
      >> Transfer_matrix 1500 1 5 15

      Warning! The program has external dependencies on the following two libraries:

      1. boost_1_66_0: https://www.boost.org/users/history/version_1_66_0.html
      2. Eigen: http://www.eigen.tuxfamily.org/index.php?title=Main_Page

    • 2018 March 13 C++ DNA-nucleosomes - C++ version of the Matlab program #2 based on the transfer-matrix formalism described in [Efremov and Yan, 2018]

      The program working range: 0 pN <= force <= 30 pN and -30 pN*nm <= torque <= 50 pN*nm. Program inputs: DNA length (nm), force (pN), torque (pN*nm), the proteins' binding energy (in k_B T units) and the upper boundary on the DNA bending/twisting modes used in the calculations, max_mode. To run the compiled program, type the following command line:

      >> Name_of_the_compiled_program DNA_length force torque binding_energy max_mode
      For example:
      >> Transfer_matrix 1500 1 5 40 15

      Warning! The program has external dependencies on the following two libraries:

      1. boost_1_66_0: https://www.boost.org/users/history/version_1_66_0.html
      2. Eigen: http://www.eigen.tuxfamily.org/index.php?title=Main_Page

    List of publications

      1. M.I. Molodtsov, E.L. Grishchuk, A.K. Efremov, J.R. McIntosh, F.I. Ataullakhanov. 2005. Force production by depolymerizing microtubules: a theoretical study. Proc. Natl. Acad. Sci. USA, 102:4353-8.

      2. [F1000 recommendation]

        Web-link: http://www.pnas.org/content/102/12/4353

      3. Artem Efremov, Ekaterina L. Grishchuk, J. Richard McIntosh,Fazly I. Ataullakhanov. 2007. In search of an optimal ring to couple microtubule depolymerization to processive chromosome motions. Proc. Natl. Acad. Sci. USA, 104:19017-22.

      4. Web-link: http://www.pnas.org/content/104/48/19017

      5. E. L. Grishchuk, I. S. Spiridonov, V. A. Volkov, A. Efremov, S. Westermann, D. Drubin, G. Barnes, F. I. Ataullakhanov, and J. R. McIntosh. 2008. Different assemblies of the DAM1 complex follow shortening microtubules by distinct mechanism. Proc. Natl. Acad. Sci. USA, 105:6918-23.

      6. [F1000 recommendation]

        Web-link: http://www.pnas.org/content/105/19/6918

      7. J.R. McIntosh, E.L. Grishchuk, M. Morphew, A.K. Efremov, K. Zhudenkov, V. Volkov, I. Cheeseman, A. Desai, D.N. Mastronarde, F.I. Ataullakhanov. 2008. Fibrils connect microtubule tips with kinetochores: a mechanism to couple tubulin dynamics to chromosome motion. Cell, 135:322-33.

      8. [F1000 recommendation]

        Web-link: https://www.cell.com/cell/fulltext/S0092-8674(08)01119-7

      9. Ekaterina L. Grishchuk, Artem K. Efremov, Vladimir A. Volkov, Ilia S. Spiridonov, Nikita Gudimchuk, Stefan Westermann, David Drubin, Geojana Barnes, J. Richard McIntosh, and Fazly I. Ataullakhanov. 2008. The Dam1 ring binds microtubules strongly enough to be a processive as well as energy-efficient coupler for chromosome motion. Proc. Natl. Acad. Sci. USA, 105:15423-8.

      10. Web-link: http://www.pnas.org/content/105/40/15423

      11. Artem Efremov*, Zhisong Wang*. 2011. Maximum directionality and systematic classification of molecular motors. Phys. Chem. Chem. Phys., 13:5159-5170.

      12. Web-link: http://pubs.rsc.org/en/content/articlelanding/2011/cp/c0cp02519d/#!divAbstract

      13. Artem Efremov*, Zhisong Wang*. 2011. Universal optimal working cycles of molecular motors. Phys. Chem. Chem. Phys., 13:6223-6233.

      14. Web-link: http://pubs.rsc.org/en/content/articlelanding/2011/cp/c0cp02118k/#!divAbstract

      15. Artem Efremov*, Jianshu Cao*. 2011. Bistability of cell adhesion in shear flow. Biophys. J., 101:1032-1040.

      16. Web-link: https://www.cell.com/biophysj/fulltext/S0006-3495(11)00884-8

      17. Hailong Lu#, Artem K. Efremov#, Carol S. Bookwalter, Elena B. Krementsova, Jonathan W. Driver, Kathleen M. Trybus, and Michael R. Diehl. 2012. Collective dynamics of elastically-coupled myosin V motors. J. Biol. Chem., 287:27753-61.

      18. Web-link: http://www.jbc.org/content/287/33/27753

      19. Karthik Uppulury, Artem Efremov, Jonathan Driver, Kenneth, Jamison, Michael R. Diehl, and Anatoly B. Kolomeisky. 2012. How the interplay between mechanical and non-mechanical interactions affects multiple kinesin dynamics. J. Phys. Chem. B, 116:8846-55.

      20. Web-link: https://pubs.acs.org/doi/abs/10.1021/jp304018b

      21. Juan Cheng, Sarangapani Sreelatha, Ruizheng Hou, Artem Efremov, Ruchuan Liu, Johan R.C. van der Maarel, Zhisong Wang. 2012. Bipedal nanowalker by pure physical mechanisms. Phys. Rev. Lett., 109:238104.

      22. [Highlighted by American Physical Society]

        Web-link: https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.109.238104

      23. Karthik Uppulury, Artem K. Efremov, Jonathan W. Driver, D. Kenneth Jamison, Michael R. Diehl,and Anatoly B. Kolomeisky. 2013. Analysis of cooperative behavior in multiple kinesins motor protein transport by varying structural and chemical properties. Cell Mol. Bioeng., 6:38-47.

      24. Web-link: https://link.springer.com/article/10.1007%2Fs12195-012-0260-9

      25. Xiaofeng Xu, Artem K. Efremov, Ang Li, Lipeng Lai, Ming Dao, Chwee Teck Lim, Jianshu Cao. 2013. Probing the cytoadherence of malaria infected red blood cells under flow. PLoS One, 8:e64763.

      26. Web-link: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0064763

      27. Zhisong Wang, Ruizheng Hou, Artem Efremov. 2013. Directional fidelity of nanoscale motors and particles is limited by the 2nd law of thermodynamics - via a universal equality. J. Chem. Phys., 139:035105.

      28. Web-link: https://aip.scitation.org/doi/abs/10.1063/1.4813626?journalCode=jcp

      29. Artem K. Efremov#, Anand Radhakrishan#, David S. Tsao, Carol S. Brookwalter, Kathleen M. Trybus, and Michael R. Diehl. 2014. Delineating cooperative responses of processive motors in living cells. Proc. Natl. Acad. Sci. USA, 111:E334-43.

      30. [Highlighted by ScienceDaily, Phys.org and several other news outlets]

        Web-link: http://www.pnas.org/content/111/3/E334

      31. Xu Yue, Chen Hu, Qu Yu-Jie, Artem K. Efremov, Li Ming, Ouyang Zhong-Can, Liu Dong-Sheng, Yan Jie. 2014. Mechano-chemical selections of two competitive unfolding pathways of a single DNA i-motif. Chin. Phys. B, 23:068702.

      32. Web-link: http://iopscience.iop.org/article/10.1088/1674-1056/23/6/068702/meta

      33. Huijuan You, Xiangjun Zeng, Yue Xu, Ci Ji Lim, Artem K. Efremov, Anh Tuan Phan, Jie Yan. 2014. Dynamics and stability of polymorphic human telomeric G-quadruplex under tension. Nucleic Acids Res., 42:8789-95.

      34. Web-link: https://academic.oup.com/nar/article/42/13/8789/1298035

      35. Mingxi Yao, Wu Qiu, Ruchuan Liu, Artem K. Efremov, Peiwen Cong, Rima Seddiki, Manon Payre, Lim Chwee Teck, Benoit Ladoux, Rene-Marc Mege, Jie Yan. 2014. Force-dependent conformational switch of alpha-catenin controls vinculin binding. Nat. Commun., 5:4525.

      36. Web-link: https://www.nature.com/articles/ncomms5525

      37. Iong Ying Loh, Juan Cheng, Shern Ren Tee, Artem Efremov, Zhisong Wang. 2014. From bi-state molecular switches to self-directed track-walking nanomotors. ACS Nano, 8:10293-304.

      38. Web-link: https://pubs.acs.org/doi/abs/10.1021/nn5034983

      39. Artem K. Efremov, Yuanyuan Qu, Hugo Maruyama, Ci J. Lim, Kunio Takeyasu, Jie Yan. 2015. Transcriptional repressor TrmBL2 from Thermococcus kodakarensis forms filamentous nucleoprotein structures and competes with histones for DNA binding in a salt- and DNA supercoiling-dependent manner. J. Biol. Chem., 290:15770-84.

      40. Web-link: http://www.jbc.org/content/290/25/15770

      41. Shimin Le, Mingxi Yao, Jin Chen, Artem K. Efremov, Sara Azimi, Mark B. H. Breese, Jie Yan. 2015. Disturbance-free rapid solution exchange for magnetic tweezers single-molecule studies. Nucleic Acids Res., 43:e113.

      42. Web-link: http://www.jbc.org/content/290/25/15770

      43. Artem K. Efremov*, Ricksen S. Winardhi, Jie Yan*. 2016. Transfer-matrix calculation of DNA polymer micromechanics under tension and torque constraints. Phys. Rev. E, 94:032404.

      44. [Editors' suggestion]

        Web-link: https://journals.aps.org/pre/abstract/10.1103/PhysRevE.94.032404

      45. Artem K. Efremov*, Ricksen S. Winardhi*, Jie Yan*. 2017. Theoretical methods for studying DNA structural transitions under applied mechanical constraints. Polymers, 9:74.

      46. [Invited review]

        Web-link: http://www.mdpi.com/2073-4360/9/2/74

      47. Miao Yu, Xin Yuan, Chen Lu, Shimin Le, Ryo Kawamura, Artem K. Efremov, Zhihai Zhao, Michael Kozlov, Michael Sheetz, Alexander Bershadsky, Jie Yan. 2017. mDia1 senses both force and torque during F-actin filaments polymerization. Nat. Commun., 8:1650.

      48. Web-link: https://www.nature.com/articles/s41467-017-01745-4

      49. Artem K. Efremov*, Fazoil I. Ataullakhanov*. 2018. Atomic-scale insights into physical mechanisms driving enzymes "working cycles". Biophys. J., 114:2027-9.

      50. [Invited commentary letter on "Motor-like properties of non-motor enzymes" paper by Slochower, D. R., and M. K. Gilson., Biophys. J., 2018]

        Web-link: https://www.cell.com/biophysj/fulltext/S0006-3495(18)30444-2

      51. Artem K. Efremov*, Jie Yan*. 2018. Transfer-matrix calculations of the effects of tension and torque constraints on DNA-protein interaction. Nucleic Acids Res., 46:6504-27.

      52. Web-link: https://doi.org/10.1093/nar/gky478

        Web-link, pre-print: https://arxiv.org/abs/1802.01437

      53. Miao Yu, Shimin Le, Artem K. Efremov, Xiangjun Zeng, Alexander Bershadsky, Jie Yan. 2018. Effects of mechanical stimuli on profilin/formin-mediated actin polymerization. Nano Lett., 18:5239-47.

      54. Web-link: https://pubs.acs.org/doi/10.1021/acs.nanolett.8b02211

      55. N. O. Alieva#, A. K. Efremov#, S. Hu, D. Oh, M. Natarajan, H. T. Ong, A. Jegou, G. Romet-Lemonne, J. Groves, M. P. Sheetz, J. Yan and A. D. Bershadsky. 2017. Force dependence of filopodia adhesion: involvement of myosin II and formins. Nat. Commun.,10:3593

      56. [F1000 recommendation]

        Web-link, pre-print: https://www.biorxiv.org/content/early/2017/09/28/195420

        Web-link: https://www.nature.com/articles/s41467-019-10964-w

      57. Shiwen Guo, Artem K. Efremov and Jie Yan. 2019. Understanding the catch-bond kinetics of biomolecules on one-dimensional energy landscape. Chem. Comm., 2:30

      58. Web-link: https://www.nature.com/articles/s42004-019-0131-6

      59. Artem K. Efremov*, Mingxi Yao, Michael P. Sheetz, Alexander Bershadsky, Boris Martinac and Jie Yan*. 2021. Application of pico-newton forces to individual filopodia reveals mechanosensory role of L-type Ca2+ channels. Submitted.

      60. Web-link, pre-print: https://www.biorxiv.org/content/10.1101/2020.10.21.346247v1

      61. Leo S. McCormack, Artem K. Efremov*, Jie Yan*. 2021. Effects of size, cooperativity and competitive binding on protein positioning on DNA. Submitted.

      * - corresponding author
      # - equal contribution
      Total number of citations, Google Scholar
      Web-link to ORCID: https://orcid.org/0000-0002-1603-610X
      H-index, Google Scholar