Research

The research activities in ARCII cover a wide range of projects centered around the question of how the organism detects the presence of “foreign” and activates protective immune responses or excessive inflammation.

 

Innate recogntion of virus infections. RNA and DNA are potent immuno-stimulatory molecules, and play important roles in activating the immune response during virus infections. In addition, there are other mechanisms of immune activation during viruses, some of which may not be known at this stage. With a primary focus on herpesviruses and human immunodeficiency virus, ARCII aims to describe the mechanisms through which the innate immune system senses virus infections. This includes identification of novel principles of immune activation, and further characterization of the nucleic acid sensing systems.

 

Innate immunological control of virus infections in vivo. With the use of clinically relevant murine model systems for virus infections, we are studying the role of the different innate recognition systems in control of infections. For this purpose we use gene-modified mice and viruses and a series of advanced methods including in vivo imaging. It is a goal to provide molecular description of key innate immunological processes in clinically relevant models. Therefore, all in vivo projects include a group consisting of basic researchers, clinicians and pathologists.

 

Signal transduction. The molecular and subcellular details on how DNA and RNA recognition transduces signals inside the cell are still not fully understood. In ARCII, we have projects that address key unresolved questions in this field. This includes knowledge on the proteins involved in signal transduction as well as the subcellular dynamics involved in signalsome assembly, protein translocation, and signal termination. To achieve our goals in this part of the project, we utilize cell biological systems, advanced biochemical and proteomic methods, as well as structural studies.

 

Regulation of innate immune response by microRNAs. Innate immune responses are positively and negatively regulated by a wealth of mechanisms leading to strong immune activation when needed and termination of the response when the infection is resolved. One class of players emerging to be involved in host control of the innate immune system is microRNAs. In this part of the project, the goal is to describe the microRNAs induced by different innate signaling pathway, and to characterize how they regulate cellular responses and how this is manipulated by viruses.

 

Immune evasion by viruses. All viruses need to evade the host immune response in order to establish infection. We have projects aiming at identification and characterization of how herpesviruses and retroviruses seek to evade the innate and inflammatory response evoked by the host. This part of the project ranges from open-minded approaches to identify novel viral immune evasion proteins, via molecular/cellular characterization of identified viral protein, to animal studies of the implications of the specific immune evasion protein on host defense.

 

Clinical impact of innate immune molecules – focus on HIV and Herpes infections. In recent years it has emerged that defects in genes encoding proteins of the innate immune system are associated with susceptibility to several infections or altered disease progression. One branch of the activities in ARCII is centered on investigating the prevalence of specific mutations in patients infected with HIV or suffering from a viral infection in the CNS. We also aim to functionally characterize the specific immune pathways in cells from these patients. With the access to patient material from the relevant patient groups and next-generation sequencing, a long-term goal of this project is to identify novel mutations associated with immunodeficiencies in humans. This project is performed in collaboration with International Centre for Immunodeficiency Diseases (ICID), Skejby Hospital.

 

Interphase with related areas. The principles in innate immune recognition of virus infections are overlapping with the mechanisms involved in other immunological processes. In ARCII, we therefore also host projects studying the role of innate sensing systems in conditions other than viral infections. The current projects in this area focus on nucleic acid recognition and intracellular bacterial infections and autoimmune diseases. 

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Revised 10.10.2012