MARE BALTICUM LECTURES - Prof. Liliya Vugmeyster

ab 2. June 2022  14-15 Uhr

Ort: Seminarraum 110

Biophysical spectroscopy of neurodegenerative diseases 

Prof. Liliya Vugmeyster

2.6.2022, 14:00 bis 15:00 Uhr, Seminarraum 110, FoBau LL&M, Albert-Einstein-Str. 25

The focus will be placed on the basics of protein folding/misfolding and a brief overview of techniques for studies of structural biology and biophysics of proteins involved in neurodegenerative diseases. In particular, we will mention circular dichroism, dynamic light scattering, transmission electron microscopy, and nuclear magnetic resonance. We will  discuss kinetic and thermodynamics factors and intramolecular forces involved in protein folding.  Example will be taken from studies of globular proteins and those involved in misfolding  processes, such as amylin, amyloid-beta, and alpha-synuclein.  

Basics of NMR approaches for studies of insoluble aggregates 

Prof. Liliya Vugmeyster

9.6.2022, 14:00 bis 15:00 Uhr, Seminarraum 110, FoBau LL&M, Albert-Einstein-Str. 25

We will discuss basics of solution and solid-state NMR methods for application of structural studies of amyloid fibrils. Chemical shift assignments are often complicated in these non-crystalline aggregates and standard triple resonance methodologies often have to be supplemented with specific isotopic labeling. Residual dipolar coupling and paramagnetic enhancement measurements can be useful as additional structural constraints in these systems. Further, we will discuss sample preparation strategies and assessment of sample quality which ultimately can be a determining factor in the success of the NMR measurements. 

Studies of flexibility of amyloid fibrils 

Prof. Liliya Vugmeyster

16.6.2022, 14:00 bis 15:00 Uhr, Seminarraum 110, FoBau LL&M, Albert-Einstein-Str. 25

We will cover the basics of protein dynamics and, in particular, flexibility in insoluble aggregates and its potential relevance in neurodegeneration and drug design strategies. We will pay special attention to NMR techniques in solution and solid-state that permit for quantification of the dynamics. Examples will include lineshape analysis, as well as more sophisticated methods such as rotating frame relaxation measurements, and saturation transfer techniques.  We will briefly consider other methods, such as cryo electron microscopy and X-ray crystallography. 

Solid-state deuterium NMR studies of dynamics in amyloid fibrils and globular proteins

Prof. Liliya Vugmeyster

24.6.2022, 13:30 bis 15:00 Uhr, Seminarraum 230, Erweiterungsbau Chemie, Albert-Einstein-Str. 27

This seminar will focus on research conducted in Dr. Vugmeyster’s group devoted to characterization of the intrinsic flexibility of amyloid fibrils spanned by amyloid-beta (1-40) peptide. Our goal is a quantitative description of internal dynamics guided by NMR data. We develop solid-state NMR geared toward deuterium nuclei, which are known to be very sensitive to dynamics processes. The analysis of the data obtained by the novel methodology is coupled to phenomenological modeling allowing for determination of the amplitudes of motions and rate constants over a wide range of temperatures. We thus obtain a detailed picture of motions in amyloid-beta fibrils of the wild-type peptide, as well as its naturally occurring mutants and aggressive post-translational modifications that are known to enhance aggregation. 

Dynamic nuclear polarization – from basics and principles towards molecular dynamics with ²H NMR

Prof. Björn Corzilius

23.6.2022, 14:00 bis 15:00 Uhr, Seminarraum 110, FoBau LL&M, Albert-Einstein-Str. 25

In this seminar aimed at non-experts, the basic principle of dynamic nuclear polarization (DNP) will be presented. We will cover the fundamental physical mechanism and give an overview over the instrumental requirements. Furthermore, DNP’s unique possibility to enhance the intensity of NMR spectra by several orders of magnitude will be presented on examples selected from current relevant research topics. Finally, we will give a perspective about future applications of DNP towards the investigation of (bio)molecular dynamics via sensitivity-enhanced 2H solid-state NMR, based on the ongoing research conducted in collaboration with Prof. Vugmeyster during the Mare Balticum Fellowship.