Thesis supervisor: Attila Gergely Végh
Web address (URL): http://www.brc.hu/biophys_protein_biophysics.php Location of studies (in Hungarian): Institute of Biophysics - Molecular, Subcellular and Microbial Biophysics Research Unit - Protein Biophysics Research Group Abbreviation of location of studies: SZBK
Description of the research topic:
Despite of modern medicine, brain related pathologies often cause life impairing profound neurological
symptoms. Most of the neoplasms found in the central nervous system are of metastatic origin. Metastasis
formation is a complex and not entirely understood process. The poorest prognosis and the most feared
complications are associated to brain metastases. Due to the lack of classical lymphatic drainage, in the
process of brain metastases formation the haematogenous route is of primordial importance. Successful
colonization of the brain involves active participation of all cellular components at the tumor
microenvironment. In addition to immune cells, cancer associated fibroblasts and endothelial cells, pericytes
are key components of the newly established tumor microenvironment, whose role in brain colonization is
largely unknown. Although several mechanisms were proposed for tumor dissemination, homing and
metastatic organotropism little is known about the mechanobiology and the role of tumor derived extracellular
vesicles in these processes.
In many cases the dissemination of tumor cells is taking place in the presence of inflammatory cytokines,
which may imbalance the outcome of organ colonization in the favor of invading cells. The exact details on
the cause and effect are only partially solved. The neurovascular unit plays crucial role in the maintenance of
the proper homeostasis of the central nervous system. Endothelial cells and pericytes are the most exposed to
mechanical stresses, therefore their mechanobiology is of primordial importance. Additionally, little is known
about the nanomechanics of pericytes and there is a major caveat in our understanding how pathological
conditions affect biophysical properties of the neurovascular unit.
Label-free chemical imaging has emerged as a non-destructive and non-invasive tool to intracellularly
detect administered drugs without exogenous labelling. Amongst the most promising applications one can
find the ability of discrimination between normal and tumor cells not only in vitro, but in vivo as well. The
need for development of new analytical techniques to study extracellular vesicles has led to the ascent of
Raman spectroscopy in this field. Our research is focused on structural, morphological and nano-mechanical
investigation of cells of the neurovascular unit, using atomic force microscopy combined with Raman
spectroscopy. Nanomechanical manifestations are strongly interconnected with biochemical functions,
therefore alterations in pathological conditions are strong indicators of underlying processes. High resolution
morphology, stiffness mapping and single cell force spectroscopy complemented with label free chemical
imaging and hyperspectral characterization are involved to reveal fundamental features about the
mechanobiology of the neurovascular unit in physiological and pathological conditions.
A more detailed characterization and description regarding the mechanobiology of the neurovascular unit
points towards development and application of more effective drugs in theranostic of neurological disease.
Besides revealing new fundamental characteristics of the neurovascular unit the results expected to emerge
from the planned experiments might lead to the development of new theranostics in neurovascular unit-related
disease.
Required language skills: English B2 Further requirements: TDK munka
Number of students who can be accepted: 1
Deadline for application: 2022-04-06
2024. IV. 17. ODT ülés Az ODT következő ülésére 2024. június 14-én, pénteken 10.00 órakor kerül sor a Semmelweis Egyetem Szenátusi termében (Bp. Üllői út 26. I. emelet).
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