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, PhD student, Cell Physics, Royal Institute of Technology
Ali Khorshidi, PhD student, Cell Physics, Royal Institute of Technology
NK cells converge lytic granules to promote cytotoxicity and prevent bystander killing.
J. Cell Biol. 2016 Dec;215(6):875-889
Microchip Screening Platform for Single Cell Assessment of NK Cell Cytotoxicity.
Front Immunol 2016 ;7():119
Microchip-Based Single-Cell Imaging Reveals That CD56dimCD57-KIR-NKG2A+ NK Cells Have More Dynamic Migration Associated with Increased Target Cell Conjugation and Probability of Killing Compared to CD56dimCD57-KIR-NKG2A- NK Cells.
J. Immunol. 2015 Oct;195(7):3374-81
Ultrasonic three-dimensional on-chip cell culture for dynamic studies of tumor immune surveillance by natural killer cells.
Lab Chip 2015 Aug;15(15):3222-31
Coordinated expression of DNAM-1 and LFA-1 in educated NK cells.
J. Immunol. 2015 May;194(9):4518-27
Distinct Migration and Contact Dynamics of Resting and IL-2-Activated Human Natural Killer Cells.
Front Immunol 2014 ;5():80
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 Apr;5(4):712-9
Classification of human natural killer cells based on migration behavior and cytotoxic response.
Blood 2013 Feb;121(8):1326-34
Visualization of custom-tailored iron oxide nanoparticles chemistry, uptake, and toxicity.
Nanoscale 2012 Dec;4(23):7383-93
Plekhh2, a novel podocyte protein downregulated in human focal segmental glomerulosclerosis, is involved in matrix adhesion and actin dynamics.
Kidney Int. 2012 Nov;82(10):1071-83
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 Jul;3(7):770-8
Flow-free transport of cells in microchannels by frequency-modulated ultrasound.
Lab Chip 2009 Mar;9(6):833-7
Membrane nanotubes physically connect T cells over long distances presenting a novel route for HIV-1 transmission.
Nat. Cell Biol. 2008 Feb;10(2):211-9