Research group Adnane Achour

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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.

Research interests

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.

Funding

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.

Group members

Adnane Achour, Professor, Group leader

Professor

Adnane Achour

Organizational unit: Group A Achour
E-mail: Adnane.Achour@ki.se
Yang Chen, Postdoc
Postdoc

Yang Chen

Organizational unit: Research Group P Brodin
E-mail: yang.chen@ki.se
Anatoly Dubnovitsky, PhD, senior scientist
Genadiy Kozhukh, Senior Research Specialist
Senior research specialist

Genadiy Kozhukh

Organizational unit: Group A Achour
E-mail: genadiy.kozhukh@ki.se
Christina Gerstner, PhD student
Research assistant on study grant

Christina Gerstner

Organizational unit: Research Group A Catrina
E-mail: christina.gerstner@ki.se
Ida Hafstrand, Doctoral student
Graduate Student

Ida Hafstrand

Organizational unit: Group A Achour
E-mail: ida.hafstrand@ki.se
Jaromir Mikes, Postdoc
Tatyana Sandalova, Researcher
Senior researcher

Tatiana Sandalova

E-mail: Tatyana.Sandalova@ki.se
Tim Schulte, PhD, Postdoc
Postdoc

Tim Schulte

Organizational unit: Group A Achour
E-mail: tim.schulte@ki.se
Lakshmikanth Tadepally, Research coordinator
Research coordinator

Lakshmikanth Tadepally

Organizational unit: Research Group P Brodin
E-mail: lakshmikanth.tadepally@ki.se
Renhua Sun, PhD, Postdoc
Postdoc

Renhua Sun

Phone: +46-(0)76-415 35 01
E-mail: renhua.sun@ki.se
Xiao Han, PhD, Postdoc
Postdoc

Xiao Han

Phone: +46-(0)73-977 26 51
Organizational unit: Department of Medicine, Solna (MedS), K2
E-mail: xiao.han@ki.se

Latest 10 publications

Structural and functional insights into peptidoglycan access for the lytic amidase LytA of Streptococcus pneumoniae.
Mellroth P, Sandalova T, Kikhney A, Vilaplana F, Hesek D, Lee M, et al
MBio 2014 Feb;5(1):e01120-13

Viral and cellular proteins containing FGDF motifs bind G3BP to block stress granule formation.
Panas M, Schulte T, Thaa B, Sandalova T, Kedersha N, Achour A, et al
PLoS Pathog. 2015 Feb;11(2):e1004659

Binding of subdomains 1/2 of PfEMP1-DBL1α to heparan sulfate or heparin mediates Plasmodium falciparum rosetting.
Angeletti D, Sandalova T, Wahlgren M, Achour A
PLoS ONE 2015 ;10(3):e0118898

Microglia-Secreted Galectin-3 Acts as a Toll-like Receptor 4 Ligand and Contributes to Microglial Activation.
Burguillos M, Svensson M, Schulte T, Boza-Serrano A, Garcia-Quintanilla A, Kavanagh E, et al
Cell Rep 2015 Mar;():

T-cell receptor-HLA-DRB1 associations suggest specific antigens in pulmonary sarcoidosis.
Grunewald J, Kaiser Y, Ostadkarampour M, Rivera N, Vezzi F, Lötstedt B, et al
Eur. Respir. J. 2016 Mar;47(3):898-909

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.

The MHC Class I Cancer-Associated Neoepitope Trh4 Linked with Impaired Peptide Processing Induces a Unique Noncanonical TCR Conformer.
Hafstrand I, Doorduijn E, Duru A, Buratto J, Oliveira C, Sandalova T, et al
J. Immunol. 2016 Mar;196(5):2327-34

Migratory activation of parasitized dendritic cells by the protozoan Toxoplasma gondii 14-3-3 protein.
Weidner J, Kanatani S, Uchtenhagen H, Varas-Godoy M, Schulte T, Engelberg K, et al
Cell. Microbiol. 2016 Nov;18(11):1537-1550

The crystal structure of the major pneumococcal autolysin LytA in complex with a large peptidoglycan fragment reveals the pivotal role of glycans for lytic activity.
Sandalova T, Lee M, Henriques-Normark B, Hesek D, Mobashery S, Mellroth P, et al
Mol. Microbiol. 2016 Sep;101(6):954-67

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

In press
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.