Ikerbasque researcher: Vadim Frolov
Our assays can help characterizing and improving the activity of already existing drugs
What research are you currently carrying out in the Basque Country?
I’m building up a research group focused on nanomechanics of biological membranes. The group is very young, having been nesting within Biophysics Unit (CSIC-UPV/EHU) for about one year. We’re open for collaborations and seeking for young and ambitious students to join us.
The main focus of our research is on biological membranes. “Nanomechanics” isn’t just a fashion label, one has to go “nano” to understand the dynamic organization of biological membrane systems.
It is well known that membranes delimit the interior of cells, the building blocks of all living organisms. In an electron microscopy snapshot membranes are seen as static barriers separating intracellular compartments created to confine chemical reactions and store essential metabolites. The structural core of such barriers is bimolecular lipid film, the lipid bilayer, which is folded in recognizable shapes of intracellular organelles, mitochondria cristae, Goldy cisternae and many others geometries familiar from biology textbooks. It is less known that those barrier, in fact, are not static construction: they are constantly rebuilt as cells transport material through membranes and adopt their morphology to changing environment. The rebuilding is conducted by specialized proteins which apply mechanical force to lipid bilayer and thus produce membrane deformation. These proteins act at much smaller scale than the characteristic sizes of the membrane compartments, i.e. at nanoscale. There the small transport vesicles, protrusions, podia and many other membrane formations with sizes ranging from 10s to 100s of nm constantly appear and disappear. The balance of the resulting membrane fluxes is at the core of the dynamic organization of membrane architecture. To understand the membrane remodeling we need to resolve and quantify these tiny membrane evens. First and foremost, they depend on the elastic properties of the lipid bilayer. Thus we aim at the mechanistic understanding of the behavior of lipid bilayer shaped in physiologically relevant geometries. We can resolve the dynamic shape transformations and measure elastic parameters of extremely small and curved membranes, e.g. short membrane nanotubes, so the name “nanomechanics” also emphasizes our experimental capabilities. Next, we study various components of the protein machinery responsibly for membrane remodeling in cells. We apply isolated proteins to engineered nanotemplates mimicking cellular membranes and monitor, using advanced microscopy and force-measurement techniques, how those proteins act on membranes, in cooperation with lipids, to create membrane curvature and shape.
You are researching in Advancing Medicine, what is the meaning of that?
Not surprisingly, the membrane nanomechanics belongs to the domain of biomedical research. This links is, perhaps, the most revealing in studies of the enveloped viruses including such dangerous human pathogens as HIV, influence and hepatitis. Their particles are small submicron containers whose wall, the envelope, is built upon the lipid bilayer taken from the host cell membrane. The mechanical properties of the envelope are the key determinants in the virus life cycle. Their changes are at the core of the temperature and humidity adaptation of the virus, they also critically affect morphological transformations of the envelope during cell penetration and egression. We reconstitute and analyze the nanomechanics of viral envelopes in our biomimetic systems using viral envelope proteins, such as HIV polyprotein Gag. By analyzing the role of critical proteins mutations and the viral lipidome we expect to obtain critical insights into molecular mechanisms of virus assembly and transmission, thus providing new rationals for the molecular design of antiviral therapeutics. Our assays can also help characterizing and improving the activity of already existing drugs. One, however, has to be extremely cautious when putting the experimental results obtained in simple reconstituted systems directly into the medical context. Our main product is the new knowledge which could help, along the long paths of bench-to-bed type collaborations, the drug development and improve our understanding of disease.
How has the acceptance of the offer from Ikerbasque influenced your scientific-research career?
After just one year in the Basque country, I would consider my current position a natural career extension, the next step. This feeling is mostly thank to the generous and timely support from Ikerbasque and the Biophysics unit. It has allowed me to smoothly transfer my key projects into the new ground and by now the new lab is running at almost full speed. It is obviously too early to weight the productivity and research accomplishments, but so far I retain substantial optimism, rare situation in the contemporary research. Importantly, it has quickly become clear that my scientific projects goes well along with the general research lines in the Biophysics Unit so that I have experienced no detachment from the scientific community, developing new collaborations and friendships instead. Basque country feels secure and comfortable, I’d probably not even need to join many others in praising the natural beauty and superb cuisine, they seem to belong here. Contrary to some opinions, I believe that such atmosphere can only stimulate productivity in research.