Project Details
Description
Maintaining a balance between activation and suppression of immune response is critical for the immune system.
Systemic Inflammatory Response Syndrome (SIRS) is an exaggerated response of the immune system and is a potentially life-threatening medical condition that is characterized by a self-harming immune response. SIRS can
be initiated by an infection (then called sepsis), or by sterile causes of cell damage, such as trauma. A hallmark of both sepsis and SIRS is the massive recruitment neutrophils from the bone marrow into the circulation.
Together with academic collaborators, ApoGlyx AB has demonstrated that genetic ablation of AQP9 is an effective way for interfering with SIRS, by preventing tissue infiltration of neutrophils. Based on these promising results, we aim to decipher the structural-functional activity of AQP9 and develop a series of compounds blocking its activity, which effects will be tested in neutrophils. The 3D structure of AQP9 will be determined with and without inhibitors by single particle cryo-EM to facilitate the possibility to execute structure-based drug design.
Furthermore, the inhibitor-effect of the newly developed compounds will be evaluated in neutrophils. Thus, when this project is executed, it will not only result in molecular understanding of AQP9, but also pave the way for novel therapeutic options towards treating sepsis and other SIRS syndromes like, acute pancreatitis and liver failure.
Systemic Inflammatory Response Syndrome (SIRS) is an exaggerated response of the immune system and is a potentially life-threatening medical condition that is characterized by a self-harming immune response. SIRS can
be initiated by an infection (then called sepsis), or by sterile causes of cell damage, such as trauma. A hallmark of both sepsis and SIRS is the massive recruitment neutrophils from the bone marrow into the circulation.
Together with academic collaborators, ApoGlyx AB has demonstrated that genetic ablation of AQP9 is an effective way for interfering with SIRS, by preventing tissue infiltration of neutrophils. Based on these promising results, we aim to decipher the structural-functional activity of AQP9 and develop a series of compounds blocking its activity, which effects will be tested in neutrophils. The 3D structure of AQP9 will be determined with and without inhibitors by single particle cryo-EM to facilitate the possibility to execute structure-based drug design.
Furthermore, the inhibitor-effect of the newly developed compounds will be evaluated in neutrophils. Thus, when this project is executed, it will not only result in molecular understanding of AQP9, but also pave the way for novel therapeutic options towards treating sepsis and other SIRS syndromes like, acute pancreatitis and liver failure.
| Status | Active |
|---|---|
| Effective start/end date | 2025/01/01 → 2028/12/31 |
Funding
- Swedish Foundation for Strategic Research, SSF
UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This project contributes towards the following SDG(s):
