Regulation of Gasdermin proteins in keratinocytes: non-cytolytic functions and post-translational control in inflammatory skin disease
Grantee: Mark Mellett, Group Leader, University of Zurich, Switzerland, Switzerland
Amount: DKK 3,373,693
Grant category: Research Grants
Year: 2025
Geography: Switzerland
Treatments for chronic inflammatory skin diseases rely on immunosuppression, which can increase infection risk and can fail to fully control disease. Keratinocytes of the epidermal barrier also actively drive inflammation. A protein family called the Gasdermins may play a key role in mediating release of inflammatory mediators from cells by forming pores in the cell membrane. At very high activity this kills the cell, but at lower activity these pores may allow controlled release of inflammatory signals, shaping communication between skin cells and immune cells.
This project will investigate:
1. How keratinocytes use Gasdermins for signaling without dying.
2. How chemical modifications fine-tune Gasdermin activity.
3. How these processes are altered in chronic inflammatory diseases, such as psoriasis and atopic dermatitis.
By identifying targets and biomarkers, this research could pave the way for new therapeutic avenues of exploration for inflammatory skin diseases.
Mitochondrial transfer in wound healing
Grantee: Sabine Werner, Professor, ETH Zürich, Switzerland
Amount: DKK 3,560,550
Grant category: Research Grants
Year: 2025
Geography: Switzerland
Chronic wounds or hypertrophic scars affect a large percentage of the population world-wide, but the therapeutic options are still limited. The development of innovative wound therapeutics requires a thorough understanding of the mechanisms underlying normal and impaired healing. This project will study a new regulatory mechanism in wound healing – the transfer of metabolically highly active cell organelles (mitochondria) between different cell types and the functional consequences for wound healing. We will use state-of-the art cell culture and mouse models to determine if mitochondrial transfer has beneficial effects on recipient cells and if this promotes the wound healing process. Through collaboration with clinical partners, we will determine the importance of our findings for normal and impaired healing in humans. The results will pave the way for the development of new wound therapeutics that target mitochondrial transfer or proteins regulated by this process.
Deciphering the coronin 1 pathway for selective inhibition of inflammatory skin diseases
Grantee: Jean Pieters, Principle Investigator, Biozentrum, University of Basel, Switzerland
Amount: DKK 3,989,627
Grant category: Research Grants
Year: 2025
Geography: Switzerland
Inflammatory skin diseases such as atopic dermatitis and psoriasis are debilitating and chronic conditions characterised by the appearance of rashes and scaly plaques. The symptoms are caused by overactivation of the immune system in which T cells play a key role. Current treatments are known to suppress the entire immune system or target pathways required for appropriate immunity and therefore are associated with significant risks for infections and cancer. Jean Pieters and his laboratory has recently defined a pathway that is selectively involved in T cell-mediated inflammatory skin disorders while being dispensable for normal immunity. Within this project Jean Pieters and his team aims to investigate the molecular mechanisms involved, and explore the potential of targeting this pathway as a therapeutic strategy for the suppression of skin inflammation while maintaining overall immunity. The results from this work may allow the delineation of hitherto unexplored and steroid-sparing therapies for inflammatory skin disorders.