The research carried out at the Laboratory is interdisciplinary - it is defined at the interface of physics, chemistry, biology and bioinformatics - and it uses both experimental and theoretical methods. The research belongs to the main trends of fundamental studies of modern biophysics and molecular biology and yet it also aims at generating applications.
The topics studied at the Laboratory deal with bionanotechnology, molecular aspects of life processes in a cell, such as protein biosynthesis and mechanical manipulation of biomolecules and virus capsids. Examples of these topics are outlined below.
Research on nanoparticles for use in cancer diagnostics and therapy
The aim of the work headed by
Bożena Sikora is to create multifunctional opto-magnetic nanoparticles for use in cancer theranostic. The up-converting infrared light to visible light nanoparticles can be used in cancer diagnostics (imaging) and to stimulate photosensitizer attached to the surface of these nanoparticles, to reactive oxygen species generation – photodynamic therapy of the cancer. The magnetic properties of the nanoparticles will be used in diagnostics - contrasts in MRI imaging, and in therapy - magnetic hyperthermia. All these methods of diagnosis and therapy will be combined in one nanoparticle. This nanoparticle will be biofunctionalized with specific antibody for the cancer, which will allow use it in targeted therapy and for detection of circulating tumor cells responsible for metastases in the blood. The research involves the production, physical characterization of nanomaterials and the study of their interaction with biological materials (cells, tissues). This research has been initiated by Prof. Danek Elbaum who retired in 2018.
Physical bases of molecular interactions
The project is lead by
Anna Niedźwiecka. Protein biosynthesis is a complex chemical and mechanical process, that engages many biological macromolecules, such as proteins, nucleic acids and their numerous ligands. The main goal of the research is to understand biophysical mechanisms of molecular interactions between regulatory terminal structures of different RNA and proteins that are crucial for gene expression. Disturbing of thermodynamic equilibria that control formation of complexes with participance of these proteins leads to malignancy, neurological and metabolic disorders, inhibition of apoptosis and immunological response. Moreover, biochemical pathways related to recognition of the RNA 5’ cap and 3’ poly(A) tail in host cells are affected by viral and parasite infections. Submolecular insight into processes of intermolecular recognition by means of experimental and theoretical biophysical methods allows us to elucidate specificity and selectivity of the mRNA 5’ cap binding by proteins, such as eIF4E, CBC and PARN in terms of thermodynamic and kinetic parameters, thus providing firm basis for rational drug design. The research performed has also led to discovery of a hierarchical mechnism of regulation of the eIF4E activity by the central translation inhibitor, 4E-BP1 protein.
Another aspect of the research is visualisation and analysis of single molecule biochemical processes in real time using microspectroscopic methods, e.g. AFM and FCS.
Membrane fusion induced by viral proteins
The studies are lead by
Remigiusz Worch. Enveloped viruses, such as e.g. influenza virus, possess glycoproteins involved in membrane fusion between the viral envelope and the endosomal membrane of the infected host cells. This event is crucial during the delivery of viral genetic material to the cell. In the case of influenza membrane fusion is mediated by hemagglutinin composed of two subunits, HA1 and HA2, which are created by the proteolytic cleavage of hemagglutinin precursor of HA0. N-terminal part of HA1 is termed as a fusion peptide (HAfp) and embeds directly into the membrane during fusion process.
We study the effects of fusion peptide length and N-terminal charge on fusion properties, structural dynamics, and binding to the membrane interface by means of various fluorescence microscopic and spectroscopic techniques. So far we developed a novel fusion visualization and quantification assay based on FLIM microscopy on giant unilamellar vesicles (GUV) and observed that HAfp1-23, having three conservative W21-Y22-G23 residues, possesses the highest fusogenic activity among all peptides studied. Moreover, we reported cholesterol-enriched domain formation induced exclusively by HAfp1-23. We speculate that lipid sorting activity of HAfp1-23 may be an important factor inducing non-planar conformations of lipids what may contribute to lowering of energy barrier for membrane fusion.
Theoretical problems in biophysics
The theoretical studies are lead by
Marek Cieplak. Much of them involves molecular dynamics simulations pertaining to large conformational changes in proteins and larger biomolecular systems and to behavior of biomolecules in the vicinity of a surface of a biological sensor, or at a phase interface, e.g. fluid-gas. Many of the simulations make use of coarse grained models and some - of all-atom models. As one of the noteworthy achievements one may consider performing a survey of mechanostability based on more than 17 000 proteins and discovery of novel mechanisms of large mechanostability. In particular, we have shown that the largest resistance to stretching should be observed in proteins in which a cysteine slipknot conformation is generated as a result of stretching. Another achievement are studies of nanoindentation of virus capsids in a molecular model that demonstrated importance of molecular aspects in the deformation of the capsids. We also conduct studies of intrinsically disordered proteins which can adopt many different conformations in physiological conditions.
In addition to the simulational studies, the research at the Laboratory is also concerned with various fundamental problems such as understanding of the process of protein folding and applicability of the two-state model that can be assessed within exactly solvable simple models. Another area of research is the interpretation of data derived from genetic microarrays on expression of all genes in an organism (such as yeast and a plant Arabidospis thaliana) after application of an external stress. The Laboratory is also engaged in numerical studies of self-organization of aggregates of biofunctionalized nanoparticles.
Amongst the main subjects of the current research of
Bartosz Różycki are (i) large conformational transitions of multi-domain proteins with intrinsically disordered regions, (ii) structure-function relationships of membrane proteins and (iii) physical mechanisms of lipid membrane deformations. In his research on multi-domain and partially disordered proteins, Dr. Różycki exploits such methods as molecular simulations and small angle X-ray scattering (SAXS) experiments. Dr. Różycki conducts his studies on membrane proteins in close collaboration with researchers from the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences. In the area of research on deformations of lipid bilayers, he collaborates with scientists from the Max Planck Institute of Colloids and Interfaces. The common denominator of these two research directions is provided by the physicochemical properties of cellular membranes. The studies on both membrane proteins and lipid membranes are motivated by the aspiration to understand the molecular mechanisms that underlie the functioning of cell membranes.
Examples of theoretical papers:
- Kinetics of protein folding in lattice models
- Kinetics of protein folding in molecular dynamics studies
- Stretching of proteins
- Genetic micro-arrays
- Structure prediction and related subjects
- Knots and entanglements
- Cellulosome
- Virus capsids
- Proteins at solid-water, fluid-fluid interfaces and molecular crowding
- Intrinsically disordered proteins
- Other
Collaborations and larger research projects
The research in the Laboratory is conducted in collaboration with other groups at the Institute of Physics of the Polish Academy of Sciences (PAS), with the Departments of Physics, Chemistry, and Biology of Warsaw University, with the Adam Mickiewicz University in Poznań, with the Warsaw medical University, Institutes of Biochemistry and Biophysica PAS, of Experimental Biology PAS, of Chemical Physics PAS, of Nuclear Physics in Cracow, the Oncology Center in Warsaw. Collaboration abroad includes Max Planck Institutes in Mainz and Potsdam, Johns Hopkins University, Pennsylvania State University, University of California San Diego, Colorado University, McGill University, Padua University, Uppsala University, University of Limerick, Ecole Polytechnique Federale Lausanne, Weizmann Institute, CSIC in Madrid, and Institute of Organic Chemistry and Biochemistry in Prague.
The Laboratory participated in many projects financed by the European Structural Funds:
POIG 1.1.2. "Quantum semiconducting nanostructures for applications in biology and medicine", POIG 2.2. "National Laboratory of Multidisciplinary Studies of Functional" (this project has been coordinated by Anna Niedzwiecka), FP7 project CellulosomPlus „Boosting lignocellulose biomass deconstruction with designer cellulosomes for industrial applications”, and finished projects Homing Plus (awarded to Joanna Grzyb) and Lider.
History of the Laboratory
The studies on modeling of proteins at the Institute of Physics have been initiated by Marek Cieplak in 1995 in the Division of Solid State Spectroscopy. The Group of Biological Physics has been formed in February 2004 within the Laboratory of X-ray and Electron Microscopy Research. The Laboratory of Biological Physics has been established in January 2010.
Former members of the Laboratory
- Graduate students
- Trinh Xuan Hoang (Ph.D. 2000)
- Joanna Sułkowska (Ph.D. 2007)
- Szymon Niewieczerzał (Ph.D. 2009)
- Wojciech Puławski (to 2008)
- Mateusz Sikora (Ph.D. 2012)
- Anna Korczyc-Baranowska (Ph.D. 2013)
- Grzegorz Nawrocki (Ph.D. 2014)
- Anna Starzyk (Ph.D. 2015)
- Karol Wołek (to 2017)
- Researchers
- Technical staff
- M.Sc. Izabela Rutkowska-Włodarczyk (to 2008)
- Dr. Anna Wałkiewicz (to 2011)
- M.Sc. eng. Marta Pędziwiatr (2014-2017)
- M.Sc. eng. Katarzyna Kopeć (2015-2017)