Molecular Mechanisms of

Functional & Pathological Amyloid Fibrils

in Health and Disease

The primary objective of the Akbey Lab is to leverage the capabilities of modern solid-state nuclear magnetic resonance (ssNMR) spectroscopy for the investigation of biofilm-forming functional bacterial amyloid (FuBA) fibrils. Our research interests involve the development of innovative NMR methodologies to push the boundaries of the current state-of-the-art techniques. By applying these cutting-edge approaches, we aim to unravel the molecular details and underlying mechanisms of these insoluble and non-crystalline proteins. Solid-state NMR has witnessed remarkable advancements in the past decade, emerging as a high-resolution and highly sensitive method. These advancements can be attributed to improvements in sample preparation techniques, hardware innovations, and the utilization of novel methods such as proton-detection and hyperpolarization (Dynamic Nuclear Polarization or DNP). These enable the investigation of not only challenging proteins in vitro but also their complex in vivo environments. Furthermore, we like to synergistically combine ssNMR with other state-of-the-art structural biology tools to gain comprehensive insights into the systems under investigation.
In our research, we focus on functional amyloid systems, which belong to a distinct class of amyloid fibrils with specific biological functions in living organisms. These systems differ from pathological amyloids, which are associated with neurodegenerative diseases such as α-synuclein or β-amyloid. Within the functional amyloid domain, we specifically investigate bacterial biofilms formed by proteins such as CsgA, FapC, TasA, and PSMs. These biofilms are significant contributors to persistent infections and antimicrobial resistance, making them critical targets for intervention. Our research efforts within the field of ssNMR-based structural biology of biofilm-forming functional amyloids aim to elucidate atomic-resolution structures and molecular dynamics information. By gaining a deeper understanding of amyloid formation, biofilm dynamics, and the complex interactions involved, we pave the way for the development of future treatments against bacterial infections and their associated antimicrobial resistance.
Members of the Akbey Lab gain extensive expertise in a diverse range of structural biology methodologies, primarily focusing on ssNMR-based protein structure and dynamics determination. Additionally, our research involves expertise in biophysics, biochemistry, recombinant protein expression and purification, physical chemistry, and other related fields. We are continually seeking motivated scientists to join our team at all levels, and we encourage interested individuals to reach out to us to explore collaboration and research opportunities.