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Investigation of protein-protein interactions to study mechanobiology of cell-matrix adhesion
Finland (FiMSIC) - University of Tampere, Tampere
Faculty of Medicine and Life Sciences
Type of Research Project
- Basic science
What is the background of the project?
This project accepts both 4 weeks and 8 weeks exchanges. Cells sense both chemical and physical signals. While chemical signals are well known and widely studied, the importance of physical signals is poorly understood. However, it has been shown that mechanical signals are essential for central cellular processes, including proliferation, differentiation and motility. We focus on integrin-associated cell adhesions and particularly to cytoplasmic integrin adaptor proteins. Failures in mechanosensing are associated with diseases such as cancer, and are currently poorly understood.
What is the aim of the project?
The aim of the project is to understand the molecular details behind cellular mechanosensing. In our case, the research aims to elucidate the connection between disease-associated mutations and their impact on cellular mechanosensing.
What techniques and methods are used?
We use molecular modelling and molecular dynamics to study the behavior of proteins under mechanical load. Biophysical protein characterization and cellular models are utilized to study these processes experimentally. The project may involve one or more of the following: Computational approach, where molecular modelling using programs such as Modeller and PyMol are used to build atomistic models of proteins, which are then subjected to molecular dynamics simulation using program Gromacs. Biophysical characterization of protein, where protein of interest is produced using recombinant methods, purified using chromatographic methods, and analyzed for its biophysical characteristics using methods such as calorimetry, spectroscopy and optical biosensoring. Cell biology experiments, where protein of interest or engineered protein is expressed in cell, monitoring the cell phenotype. The analysis may focus on subcellular localization of the protein, cell migration, cell polarity, cell traction force, cell invasion capability or protein interactions within cells.
What is the role of the student?
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
The student will obtain training to participate wet lab experiments and interpretation of the results. The student will report the findings made to supervisor and communicate them in research group meetings. The student will work on computational methods such as molecular modelling using programs such as Modeller, PyMol and Gromacs. The student will work on protein production, protein purification and biophysical characterization as well as cell biology experiments using methods mentioned in the tehniques and methods -part.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Student may participate the seminars organized 1-2 x month + participate the meetings of the research group (2x month)
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a scientific report - The student’s name will be mentioned in a future publication
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
It would be important to have some basics training in biochemical methods and/or cell culture methods.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Pre-Medical students from the American-British system
- Mechanotransduction in talin through the interaction of the R8 domain with DLC1. Haining AWM; Rahikainen R; Cortes E; Lachowski D; Rice A; von Essen M; Hytönen VP; Del Río Hernández A. PLoS Biol. 2018 Jul 20;16(7):e2005599. doi: 10.1371/journal.pbio.2005599.
- Mechanical unfolding reveals stable 3-helix intermediates in talin and α-catenin. Mykuliak VV; Haining AWM; von Essen M; Del Río Hernández A; Hytönen VP. PLoS Comput Biol. 2018 Apr 26;14(4):e1006126. doi: 10.1371/journal.pcbi.1006126.
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