Research group Adnane Achour
Structural and Biophysical Immunobiology. Mass-Cytometry.
Expertise and Importance of the recruitment for the Department of Medicine in Solna and the Karolinska Institutet
The expertise of the Achour research group is multiple, making use of a combination of structural biology, biophysical characterization and immunology to understand the function of pathogen-derived virulence-associated proteins as well as to define novel procedures that allow for the design of MHC-class I-restricted altered peptide ligands. Deep knowledge in molecular biology, biochemistry, X-ray crystallography and Small Angle X-ray Scattering is combined with expertise in functional in vitro and in vivo immunological assays as well as a large panel of different biophysical technologies, including Surface Plasmon Resonance and Isothermal Titration Calorimetry, to define and study how proteins interact with other ligands, how they manipulate and distort immune responses and finally how one may reestablish efficient immunological responses and/or define novel inhibitors.
Cellular communication is achieved through the interactions of specialized receptor molecules at the cell surface and their ligands. Our research group uses X-ray crystallography and Small Angle X-ray Scattering (SAXS) to study receptor-ligand interactions between T or NK cell receptors and Major Histocompatibility Complex (MHC) molecules, as well as bacterial adhesins and virulence-associated molecules.
All of our studies are complemented by a wide array of immunological assays as well as an extensive amount of biochemical techniques, including surface plasmon resonance and circular dichroism. By understanding the structural details of proteins, we can probe their function and potentially design artificial ligands that could modulate their function and activity.
Development of MHC class I-binding altered peptides for vaccines
Using a combination of structural biology and immunology, our research group has defined a procedure that allows for the design of altered peptide ligands (APLs) that bind with high affinity to MHC-I ligands. The immunogenic APLs act as mimotopes of disease-associated non-immunogenic epitopes, and enhance the stability of MHC-I molecules. Importantly, these modified peptides conserve a structural conformation similar to the wild-type infection-derived or non-immunogenic tumor-associated peptides.
Studies performed within our laboratory demonstrate that the induced immunogenic CD8+ T cells cross-react with the original peptides, resulting in enhanced in vitro and in vivo responses. Studies of the functional and structural consequences of substitutions in APLs on CD8 responses directed towards tumor associated antigens and viral immune escape variants are ongoing. The effects of similar modifications are also tested on modulation of recognition by natural killer (NK) cells.
Determination of the crystal structures of Streptococcus pneumoniae-associated virulence factors
Streptococcus pneumoniae (pneumococcus) is a major human pathogen and the leading cause of pneumoniae, bacteremia and meningitis in adults. The increasing number of antibiotic-resistant strains and the suboptimal clinical efficacy of available vaccines hamper control of this pathogen. We focus on novel virulence-related pneumococcal proteins that could be used as potential targets for future drugs.
Determination of the crystal structures of main allergens
Our research group has a strong interest in determining the crystal structures of allergens that provide important information regarding the initiation of allergy responses. These three-dimensional structures are used as templates for the design of hypoallergenic variants and to identify main antibody epitopes.
The Achour research group has been financial funded during the last 13 years by the Swedish Research Council (both Medicine and Natural Sciences), the Swedish Cancer Society (Cancerfonden), the Swedish Foundation for Strategic Research, the Wallenberg Foundation, VINNOVA, and the Swedish Childhood Cancer Foundation as well as a large quantity of minor foundations.
Adnane Achour, Professor, Group leader
|Yang Chen, Postdoc|
|Anatoly Dubnovitsky, PhD, senior scientist|
|Genadiy Kozhukh, Senior Research Specialist|
|Christina Gerstner, PhD student|
|Ida Hafstrand, Doctoral student|
|Jaromir Mikes, Postdoc|
|Tatyana Sandalova, Researcher|
|Tim Schulte, PhD, Postdoc|
|Lakshmikanth Tadepally, Research coordinator|
|Renhua Sun, PhD, Postdoc|
|Xiao Han, PhD, Postdoc|
Latest 10 publications
Elien M. Doorduijn, Marjolein Sluijter, Bianca J. Querido, Claudia C. Oliveira, Adnane Achour, Ferry Ossendorp, Sjoerd H. van der Burg and Thorbald van Hall (2016) Absence of central tolerance enables therapeutic exploitation of a CD8 T cell subset targeting hidden self-antigens. Journal of Clinical Investigation, 126(2):784-94.
Tim Schulte, Lifeng Liu, Marc Panas, Bastian Thaa, Nicole Dickson, Benjamin Götte, Tatyana Sandalova, Adnane Achour* and Gerry McInerney (2016) Combined structural, biochemical and cellular evidence demonstrates that both FGDF motifs in nsP3 of Semliki Forest and chikungunya viruses are required for efficient replication. Open Biology, in press. * Shared last author
|Davide Angeletti, Tatyana Sandalova, Mats Wahlgren and Adnane Achour (2015) Identification of the heparin sulphate binding site in the Plasmodium falciparum rosetting domain NTS-DBL1α of PfEMP1. Plos One, in press.|
|Miguel Angel Burguillos, Martina Svensson, Tim Schulte, Albert Garcia-Quintanilla, Edel Kavanagh, Martiniano Santiago, Antonio Boza-Serrano, Nikenza Viceconte, Maria Jose Oliva-Martin, Emma Salomonsson, Lahouari Amar, Anette Persson, Adnane Achour, Elisabet Englund, Hakon Leffler, Jose Luis Venero, Bertrand Joseph and Tomas Deierborg (2015) Microglia-secreted Galectin-3 acts as a Toll-like receptor-4 ligand and contributes to microglial activation. Cell Reports, in press.|