Björn Önfelt Project
The primary focus of our research is to understand the processes in which Natural Killer cells (NK cells) and T-cells communicate with and eliminate cells that are potentially harmful to the body. The heterogeneity regarding the receptor expression patterns and effector functions of the target cell populations makes these phenomena utterly complex. Most immunological setups in this field focus on readouts based on the average of the cell population. Thus far we have pursued the goal of developing new assays that can be used in academic research as well as the pharmaceutical and health care industry. We focus on approaches that provide the means to study the behavior of single cells and small subpopulations of cells. In the future this will enable us to effectively study how individual NK cells respond to different conditions.
Cell mediated immunity by NK cells is achieved by the formation of an immune synapse. This is a highly organized sub cellular interface between the NK cell and the target cell involving a number of communication processes leading to secretion of cytotoxic molecules and killing of the target cell. To address heterogeneity of NK cell populations we have developed two microchip-based approaches for high resolution imaging of individual NK cells or NK cell-target-cell conjugates over extended periods of time. The cells are restricted in space by miniature wells organized in an array format or an ultrasonic cage, which promotes and facilitates studies of cell-cell interactions.
In order to characterize the intermittent movements of lymphocytes we implement a method that has previously been used in single molecule tracking studies. That makes it possible to automatically detect and quantify the periods of transient migration arrest that is typical for these cells. The method allows quick assessment and quantification of altered migration properties of cells during e.g. drug treatments and infections.
Project Group Members
Bruno Vanherberghen, Postdoc, Cell Physics, Royal Institute of Technology
Thomas Frisk, Postdoc, MTC Karolinska Institute and Cell Physics, Royal Institute of Technology
Karolin Guldevall, ph.d. student, Cell Physics, Royal Institute of Technology
Ali Khorshidi, ph.d. student, Cell Physics, Royal Institute of Technology
Links
Selected Publications
Natural killer cell inhibitory receptor expression in humans and mice: a closer look.
Front Immunol. 2013;4:65.
Live cell imaging in a micro-array of acoustic traps facilitates quantification of natural killer cell heterogeneity.
Integr Biol (Camb). 2013 Feb 22
Classification of human natural killer cells based on migration behavior and cytotoxic response
Blood. 2013 Jan 3
Visualization of custom-tailored iron oxide nanoparticles chemistry, uptake, and toxicity.
Nanoscale. 2012 Oct 16. [Epub ahead of print]
Novel Microchip-Based Tools Facilitating Live Cell Imaging and Assessment of Functional Heterogeneity within NK Cell Populations.
Front Immunol. 2012;3:300. doi: 10.3389/fimmu.2012.00300
Plekhh2, a novel podocyte protein downregulated in human focal segmental glomerulosclerosis, is involved in matrix adhesion and actin dynamics
Kidney Int. 2012 Jul 25. doi: 10.1038/ki.2012.252.
A silicon-glass microwell platform for high-resolution imaging and high-content screening with single cell resolution
Biomed Microdevices. 2011 Aug;13(4):683-93.
Analysis of transient migration behavior of natural killer cells imaged in situ and in vitro
integr Biol (Camb). 2011 Jun 20. [Epub ahead of print]
Live cell linear dichroism imaging reveals extensive membrane ruffling within the docking structure of Natural Killer cell immune synapses
Biophysical Journal 96, L13, 2009
Flow-free transport of cells in microchannels by frequency-modulated ultrasound
Lab on a Chip 9, 833, 2009
Membrane nanotubes physically connect T cells over long distances presenting a novel route for HIV-1 transmission
Nature Cell Biology 10, 211, 2008
