Is your heart pumping fast because you are excited about biophysical research? Good, that means you’re alive! But blood flow can also be a complex, chaotic environment that the proteins in our blood stream must adapt to. Turbulent blood flow has been linked to the progression of amyloid disease, which in new estimates affects 25% of the elderly population, more than previously assumed. In some aggressive hereditary variants amyloidosis can also affect the younger population. Dr. Irina Ritsch’s research aims to understand how shear stresses experienced in fluid flow affect proteins at the molecular level. Her research takes inspiration from other animal species including birds whose hearts can routinely beat orders of magnitude faster than human hearts. Understanding their protein adaptations may lead to future strategies to mitigate flow induced stress.
- Post-doctoral researcher at Scripps Research, La Jolla, USA
- JSPS Strategic Fellow at Kyoto University, Japan
- PhD in Electron Paramagnetic Resonance at the Laboratory of Physical Chemistry, ETH Zurich, Switzerland
- Erasmus exchange student at Trinity College, Dublin, Ireland
- BSc and MSc in Interdisciplinary Sciences at ETH Zurich, Switzerland
Branco Weiss Fellow Since
Structural Biology, Biophysics
Scripps Research, La Jolla, USA
Modern structural biology has given us powerful experimental and computational tools to routinely solve the static aspects of protein structures. It is now time to see their interactions and dynamics in their chaotic native environments. Specifically, Dr. Ritsch’s research is focused on proteins in flow conditions, such as found in the blood stream. As we age, the flows in our bodies begin to change, which is frequently linked with disease. Her project aims to reach a better understanding of the effects of flow conditions at the individual protein level.
Dr. Irina Ritsch’s study will focus on the aggregation of the human blood plasma protein transthyretin (TTR), which is associated with spontaneous and inherited amyloidosis. Preliminary experiments have revealed that TTR aggregation is weakly observed in moderately strong shear flow, and even more so in turbulent flow conditions. Excitingly, modifications of the TTR amino acid sequence found in an ortholog variants from hummingbirds are protective against aggregation under flow.
In this project Dr. Ritsch will combine in vitro biophysical methods including light scattering, fluorescence, magnetic resonance spectroscopy, and electron microscopy to investigate the detailed kinetics and aggregation intermediates of different variants of TTR under turbulent flow stress conditions. Development of a robust experimental protocol to apply controlled flows, and a better structural and dynamic understanding of early stage intermediates will allow Dr. Ritsch to evaluate how currently available small drugs designed to prevent or slow down TTR aggregation perform in the context of flow induced aggregation. In parallel, comparing the stabilized hummingbird variant to known amyloidogenic variants of human TTR may lead to novel therapeutic strategies for aggregation prevention.
Following up on the protein[nbsp] aggregation aspects of TTR, Dr. Ritsch will in a complementary approach investigate the role of flow in the protein’s native function as a thyroid hormone and retinol binding protein carrier, and screen for other protein adaptations to flow and shear stress.