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university of tampere: faculty of medicine and life sciences: research:
Lääketieteen ja biotieteiden tiedekuntaUniversity of TampereLääketieteen ja biotieteiden tiedekunta
Vesa Hytönen - Protein Dynamics

About research group

Proteins adapt conformationally to their environment in response to chemical and physical signals arising from interactions with other molecules, and as a result of chemical modifications. Therefore, conformational changes in proteins are often essential for the protein function. The Protein Dynamics Group uses experimental and computational methods to elucidate the relation between protein conformation and function.

We study structural dynamics of the proteins in cellular adhesion sites called focal adhesions. In particular, we try to understand the mechanisms behind cellular mechanosensing. These studies involve cellular models, tailored hydrogel substrates for cell adhesion studies, protein engineering and molecular dynamics simulations. We collaborate in this project with University of Geneva.

Another approach to understand the impact of environment on protein conformation is a project where we study the effects of electric fields on protein structure and function. This research is performed in collaboration with University of Jyväskylä and Technical University of Tampere.

We utilize a broad set of biophysical characterization methods in our research, including calorimetry, biosensors and spectroscopic methods. Recombinant proteins and protein engineering are in routine use, and this expertise is utilized in research aiming for biofunctionalized materials, focusing on nanocellulose and various metals. In this field, we collaborate with VTT Espoo, University of Jyväskylä and Technical University of Tampere.

Our research group is also involved in projects developing novel diagnostic tools and vaccines. This work has a main focus on viruses, with the recently launched THERDIAB-project aiming to develop novel molecular tools to fight against enteroviral diseases and type 1 diabetes. This project is performed in collaboration with Karolinska Institutet.

Recent results

Protein interplay in atherosclerosis

Increased expression of histone deacetylase 9 (HDAC9) and matrix metalloprotease 12 (MMP12) in carotid artery wall has been linked to the development of atherosclerosis and adverse clinical outcome of its treatment. Here, we utilized genome-wide expression analysis to study the association of MMP12 and HDAC9 expression in atherosclerotic plaques with plaque stability and with macrophage and smooth muscle cell markers. We found an association of HDAC9 and MMP12 expression in carotid artery plaques and identified M4 macrophages as a possible source of the increased MMP12 and HDAC9 expression in these plaques. Immunohistochemistry of tissue sections from artery plaques and healthy arteries confirmed colocalization of HDAC9 and MMP12 signals with each other and with the macrophage markers. These results suggest that M4 macrophages may play an important role in the development and progression of atherosclerotic plaques in arteries.

Oksala et al.
Synergistic Expression of Histone Deacetylase 9 and Matrix Metalloproteinase 12 in M4 Macrophages in Advanced Carotid Plaques.
Eur. J. Vasc. Endovasc. Surg. 2017, 53(5), 632-640

http://www.sciencedirect.com/science/article/pii/S1078588417301259

Talin stability influences cellular functions

Force-controlled unfolding of a central cell-matrix adhesion protein called talin has been suggested to act as a cellular mechanosensor, but so far the effects of talin destabilization have not been studied. In this study, we designed a panel of point mutations destabilizing a mechanosensitive subdomain in talin rod and analyzed the phenotypes induced by them in cultured fibroblast cells. Talin destabilization was found to affect adhesion protein dynamics, cell migration rate and ECM substrate sensing. These results provide evidence into how the controlled talin rod domain unfolding acts as a key regulator of adhesion structure and function in adherent animal cells.

Rahikainen et al.
Mechanical stability of talin rod controls cell migration and substrate sensing.
Scientific Reports 2017, 7, 3571

https://www.nature.com/articles/s41598-017-03335-2.epdf

 

Novel coxsackievirus vaccine

Vaccination would be powerful tool to prevent CVB associated diseases. We developed an efficient vaccine production protocol for CVB vaccines by optimizing virus production, purification and formulation steps. Administration of formalin-inactivated CVB1 induced a strong, virus-neutralizing antibody response in vaccinated mice, and protected mice against CVB1 infection. Altogether, these results provide valuable information for the development of new enterovirus vaccines for human use.

Hankaniemi et al.
Optimized production and purification of Coxsackievirus B1 vaccine and its preclinical evaluation in a mouse model Vaccine. 2017

Free access to full article: https://authors.elsevier.com/a/1VBag,60n7SQ~j

Article: www.sciencedirect.com

Stretching of talin rod

Using single-molecule atomic force microscopy (smAFM), we show that the entire talin rod can be unfolded by mechanical extension, over a physiological range of forces between 10 and 40 pN. We also demonstrate, through a combination of smAFM and steered molecular dynamics, that the different bundles within the talin rod exhibit a distinct hierarchy of mechanical stability. These results provide a mechanism by which different force conditions within the cell control a graduated unfolding of the talin rod. Mechanical unfolding of the rod subdomains, and the subsequent effect on talin's binding interactions, would allow for a finely tuned cellular response to internally or externally applied forces.

Haining et al.

All Subdomains of the Talin Rod Are Mechanically Vulnerable and May Contribute To Cellular Mechanosensing.

ACS Nano. 2016, 10(7), 6648-58.
http://pubs.acs.org/doi/abs/10.1021/acsnano.6b01658

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Previous results archive

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Biocenter Finland plays important role in our operation and
we provide services in protein production and protein analysis

 
Faculty of Medicine and Life Sciences
Arvo Ylpön katu 34
33520 Tampere, Finland
Maintained by: webmaster@biomeditech.fi
Last update: 26.6.2017 9.23 Muokkaa

University of Tampere
+358 3 355 111
registry@uta.fi


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