DyNaMo - Dr. Fidan Sumbul

Dr. Fidan Sumbul

Current position

Post-doctoral Researcher, Force Microscopy Group @LAI, U1006 Inserm, Marseille-France

Educational Background

2016 – PhD in Chemical Engineering – Computational Structural Biology Curriculum, Department of Chemical Engineering, Bogazici University, Istanbul, Turkey

Thesis Title: An Integrated Computational and Experimental Approach to Allosteric Control Mechanism of Biomolecular Processes, Supervisor: Prof. Dr. Türkan Haliloglu

2008 – M.S. in Chemical Engineering – Computational Structural Biology Curriculum, Department of Chemical Engineering, Bogazici University, Istanbul, Turkey

Thesis Title: Protein-Protein Binding Site Predictions using Machine Learning Tools , Supervisor: Prof. Dr. Türkan Haliloglu

2006 – B.S. in Chemical Engineering – Department of Chemical Engineering, Bogazici University, Istanbul, Turkey

Major Research Interests

Computational Structural Biology and Biophysics with the focus on

Integrative Structural Modeling
Biomolecular Interactions
Conformational Dynamics
Allosteric Regulations
Molecular Simulations
Atomic Force Microscopy (Force Spectroscopy)

Current Projects

Dynamics and Mechanics of Fast Leukocyte Adhesion

Cell adhesion has a crucial role in inflammation, immunological responses and cancer cell metastasis. Leukocytes, travelling at high velocities with the blood flow, slow down within a few milliseconds by interacting with the vessel wall. This process is mediated by cell adhesion molecules. Therefore, the bonds formed are subjected to important mechanical forces that develop at high rates. This fast dynamical process of bond formation and rupture is crucial during the early steps of inflammation. However, little is known about the mechanical response of individual adhesion complexes at high physiological rates. My main goal in this project is to determine the molecular mechanisms of the unbinding process of adhesion complexes at high loading rates via an integrated experimental and computational approach. I'm using high-speed atomic force microscopy (HS-AFM) to investigate the mechanics of fast leukocyte adhesion process and advanced computational methods (steered molecular dynamics and metadynamics simulations) to complement the experimental results, providing an atomic description of the unbinding and conformational transition processes during adhesion and activation.

Effect of the Cantilever Response Time on Measured Forces

Dynamic force spectroscopy (DFS) measures the forces required for bond rupture or protein unfolding by applying different loading rates. Experimentally, the biomolecule is attached to a probe moved at a range of velocities. Recent theoretical developments have predicted the contribution of the finite response time of the probe. To assess this effect on the unfolding forces from DFS, we are carrying out high-speed force spectroscopy on titin I91 using cantilevers with a range of response times (milli- to microsecond). In good agreement with predictions, our preliminary results suggest a non-negligible effect when the unfolding time approaches the response time of the cantilever. This effect may overestimate the unfolding forces of titin I91 by 10-20% at the highest speed accessible to each cantilever.

Selected publications

(*corresponding author, ^¶equal contribution) Google Scholar profile / Researchgate Profile

M. Karageorgi, Groen S. C., Sumbul F., Pelaez J. N., Verster K. I, Aguilar J. M., Hastings A. P., Bernstein S. L., Matsunaga T., Astourian M., Guerra G., Rico F., Dobler S., Agrawal A. A., Whiteman N. K., 2019, Genome editing retraces the evolution of toxin resistance in the monarch butterfly, Nature, 1-4
Sumbul F., A. Marchesi, F. Rico, 2018, History, rare, and multiple events of mechanical unfolding of repeat proteins, The Journal of Chemical Physics, 148 (12), 123335.
Sumbul F.^¶, S. E. A. Ozbabacan^¶, T. Haliloglu, 2016, Allosteric dynamic control of binding, Biophysical Journal, Biophysical Journal 109(6) 1190-1201.
Sahillioglu, A. C.^¶, F. Sumbul^¶, N. Ozoren, and T. Haliloglu, 2014, Structural and dynamics aspects of ASC speck assembly. Structure 22:1722-1734.

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