High-speed Atomic Force Microscopy to unravel the dynamics of biomolecular processes
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MSCA-22-RWillaert01
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Beschrijving van het project
The advent of atomic force microscopy (AFM) nanoimaging techniques heralded a new era for imaging and analysis of biomolecules and cells. Due to recent developments in AFM by the development of high-speed AFM, biomolecular and cell surface processes can be imaged at high resolution and dynamically in physiological conditions at video rate (> 1 fps).
Potentials project topics include:
- Protein-DNA interactions (such as to study human topoisomerase II – DNA interaction)
- Construction of DNA origami structures to analyze protein-DNA interactions, enzyme actions, and the development of diagnostic assays
- High-speed imaging of cell surfaces and mechanical characterization of cells (microbial and mammalian cells).
- Self-assembly of proteins (peptides) in 2D and 3D on a surface.
As a future MSCA fellow, you will prepare the Marie Sklodowska Curie - Individual Fellowship proposal with the support of the Vrije Universiteit Brussel (VUB) and the supervisor Prof. Ronnie Willaert. In case of successful application, you will be hosted within the Structural Biology Brussels (SBB) research group of the VUB, the International Joint Research Group VUB-Ecole Fédérale de Lausanne (Switzerland) BioNanotechnology & Nanomedicine (NANO), and the Alliance Research Group VUB-UGent NanoMicrobiology (NAMI); collaborations with PD Dr. MD Sandor Kasas (EPFL, Lausanne, Switzerland), prof. Bart Devreese (Lab Microbiology, Ghent University, Belgium). For this topic, collaboration with the lab of Biotechnology of Prof. Andre Skirtach (Ghent University, Belgium) is possible since we recently setup a joint AFM platform with at the Ghent University site a Bio-AFM JPK NanoWizard 4 (including vibrational spectroscopy and the FluidFM setup) and at the VUB site a high-speed AFM (Bruker JPK NanoWizard Ultraspeed 2); collaboration with the AFM lab of Dr. Sandor Kasas is also possible.
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Structural Biology Brussels
Structural Biology Brussels (SBB) is headed by Prof. Dr. ir. Jan Steyaert and focusses on research in structural biology. We study the structure of proteins and DNA from the molecular to the atomic level. By determining the position of atoms in a macromolecule (proteins, for example, contain thousands of atoms) we can derive how such molecules can act as tiny machines, and determine how they interact with each other. The end goal of this research is to unravel the complex machinery that makes cells work.
Our work on fundamental aspects of biology and biochemistry also leads to important industrial and biomedical applications. If you know how a protein works, you can also find out why these tiny machines sometimes fail to work as they should. For example, if we learn more about the molecular cause of certain hereditary diseases, or the reason why bacteria can resist antibiotics, then this serves as the first step in rational drug design: developing novel drugs based on knowledge of protein structure and their mode of action.
SBB is a large research groep with about ten principal investigators. This critical mass allows us to employ many complementary state-of-the-art techniques in the field, whose results we combine to obtain a picture of the macromolecules under study that is as accurate and correct as possible. The most important technique we use is X-ray diffraction on protein crystals, as well as NMR spectroscopy, SAXS and electron microscopy. These are supported by our expertise in biochemistry, protein engineering, molecular biophysics and computational structural biology.
At the SBB we also perform fundamental research into the crystallisation and nucleation of biological macromolecules; this goes as far as employing microgravity in the International Space Station.
Finally, the SBB is part of the Structural Biology Research Center (SBRC). The SBRC is part of the Vlaams Instituut voor Biotechnologie (VIB), an institute which encompasses leading research groups with biotechnology interests over the Flemish universities. The aim of the VIB is to translate results from fundamental research in medicine, agriculture and industry.