Microscopy of protein nano-dynamics

Understanding the dynamics of the internal organization of macromolecules, especially proteins, in their natural environment is a critical step toward understanding their biological function. However, experimental methods in this area face a number of fundamental obstacles, be it the spatial resolution of optical arrays, the speed of sensing fluorescence signals, or averaging over a heterogeneous set of molecules.

This thesis will use a novel method for optical imaging of scattered light on single molecules and scattering labels developed by the Nano-optics research team. The initial systems to be investigated will be microtubule-associated motor proteins such as Kinesin-1, Ase1, and Tau. The scope of the research project will be to experimentally study changes in the spatial arrangement of proteins at the single-molecule level in real time with high spatial and temporal resolution on the order of nanometre units and microseconds. While contributing to the development and validation of the measurement method, the main goal of the work is to describe the dynamics and mechanical function of the basic building blocks in biological systems.

The Ph.D. program can be integrated into the 1st Topical Partner Cluster (TPC) „Cytoskeletal Dynamics Across Scales: From molecular biophysics to organismal development“ associated with the Dresden International Graduate School for Biomedicine and Bioengineering (DIGS-BB).

Ph.D. student can benefit from access to combined research infrastructure, techniques, training, lab rotations, and joint summer schools. DIGS-BB TPC provides expert mentoring and thesis supervision by each student’s Thesis Advisory Committee (TAC). Each TAC comprises three experts usually representing different disciplines and research institutions. The TAC will accompany each Ph.D. student throughout the thesis work for a maximum duration of 4 years. More information at https://www.digs-bb.de/tpc/cytoskeletal-dynamics-across-scales

[1] M. Vala, L. Bujak, A.G. Marin, K. Holanova, V. Henrichs, M. Braun, Z. Lansky, M. Piliarik, Nanoscopic Structural Fluctuations of Disassembling Microtubules Revealed by Label-Free Super-Resolution Microscopy, Small Methods (2021) 2000985

[2] H. Robert, K. Holanová, Ł. Bujak, M. Vala, V. Henrichs, Z. Lánský, M. Piliarik, Fast photothermal spatial light modulation for quantitative phase imaging at the nanoscale, Nature Communications 12 (2021) 2921

[3] M. Piliarik, V. Sandoghdar, Direct optical sensing of single unlabelled proteins and super-resolution imaging of their binding sites, Nature Communications 5 (2014) 4495

[4] M. Vala, M. Piliarik, Weighing single protein complexes on the go, Nature Methods 18 (2021) 1159–1160