The visit to the Center was one of the tasks involved in the project in which I am the principal investigator, funded with the grant won for the proposal submitted in the NCN Sonatina call W pogoni za HARE: określenie mechanizmu wiązania nowych i niezbadanych ligandów receptora kwasu hialuronowego, stabiliny-2 (Chasing HARE: Determining the mechanism by which the hyaluronic acid receptor, stabilin-2', binds new and previously uncharacterized ligands).
Both institutions, the Institute of Structural Biology and the Bavarian NMR Center, where I completed my internship, are headed by prof. Michael Sattler, a prominent researcher specializing in NMR spectroscopy, X-ray crystallography, and cryo-electron microscopy. He leads a research group of several dozen people, who meet for weekly seminars to discuss and share their findings. The remarkable thing is the general atmosphere of cooperation and opportunities to learn from others how to operate advanced laboratory equipment, thereby making the use of resources very efficient. The only constraint on how a technique is used is the limit of individual ingenuity.
The purpose of the ongoing Sonatina project is to study the structure and explore new functions of the human Stab2/HARE (Hyaluronic Acid Receptor for Endocytosis) protein. The main reason for undertaking research on this receptor is its significant involvement in many physiological and pathological processes (e.g., in carcinogenesis) and in drug delivery to cells. For example, the protein is found on the surface of cells lining blood vessels in the liver, lymph nodes, and other organs. It is what is known as a scavenger receptor, which means that it is on the identifies various molecules circulating in the bloodstream and ‘sweeps’ them into cells.
Recent findings have shown that this protein can be used to introduce molecules with potential therapeutic effects into cells, or molecules that can act as drug carriers. Delivering active molecules into cells remains a great challenge for medicine, and the design of new therapies and medical procedures should always take into consideration potential side effects as well. To date, only a small fragment of the Stab2 structure has been understood, with the rest still waiting to be uncovered.
During the internship, I succeeded in obtaining a fragment of the receptor, the Link domain responsible for hyaluronic binding among others, which could lead to the determination of the spatial structure of this important domain. This would provide valuable information to help understand the function of Stab2 in removing molecules from the bloodstream and the nature of their competition for this as yet enigmatic receptor.
Furthermore, I also had the opportunity to meet Dr. Grzegorz Popowicz's research group during the internship, to work on a project concerning the structure of proteins responsible for mitochondrial division. For this purpose, the rapidly developing method of cryo-electron microscopy was used, which allows you to observe protein molecules directly off a purposely frozen sample. Achieving this kind of resolution should doubtless ensure future insights into many processes and structures of biomolecules that have hitherto remained unresolvable with other available techniques.
Aleksandra Twarda-Cłapa
Institute of Molecular and Industrial Biotechnology
HARE Hyaluronic Acid Receptor for Endocytosis