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Grant category: Serendipity Grants

Year: 2025

Geography: Denmark

Thomas Sicheritz-Pontén serendipitously found that ~15% of sequenced phages encode two adjacent, independently active endolysin genes, often with distinct catalytic and binding domains. In one example, each enzyme is active on its own, and modelling suggests they also form a complex. While developing a custom endolysin predictor incorporating gene neighbourhood context, he detected genomic patterns missed by other tools. Most studies focus on individual lysins or domains, overlooking adjacent full-length endolysin genes. His large-scale analysis of 21k phage genomes revealed this hidden trend and a possible unrecognised lysis strategy hiding in plain sight.

The project will begin with phage AA002, which infects Staphylococcus hominis, a contributor to human body odour. Thomas Sicheritz-Pontén will clone, express, and purify its two endolysins, assess their activity alone and in combination, and investigate synergy and complex formation. Structural modelling will provide mechanistic insight. In parallel, he will mine publicly available phage genomes to identify additional dual-endolysin systems and prioritise further candidates for testing on skin-associated bacteria under skin-like conditions.

This study will define a novel category of cooperative phage lytic enzymes, offering insights into phage genome organisation and enzyme evolution. Beyond fundamental discovery, these enzymes could serve as precise, microbiome-friendly actives for non-antibiotic applications such as next-generation deodorants.

Grant category: Serendipity Grants

Year: 2025

Geography: Denmark

“Stretch-mediated tissue expansion” is used to grow extra skin during breast reconstruction. A mouse model mimicking this clinical process was used to unravel fibroblast-epithelial crosstalk supporting keratinocyte self-renewal. Unexpectedly, the research project found that stretching alters gene expression in Schwann cells, which support nerve function, and reduces touch sensitivity. However, how stretching impacts skin nerves and sensation remains unclear. In light of this serendipitous discovery, the project now plans to investigate how Schwann cells contribute to the regeneration and re-innervation of peripheral sensory neurons in stretched skin.

The new research project – SkinSense – will explore how stretching affects peripheral sensory neurons and Schwann cells, which are key to skin sensation. Single-cell transcriptomics and high-resolution imaging will be used to study how peripheral sensory neurons are affected in terms of structure, function, and repair. Based on these findings, gene therapy approaches using adeno-associated viruses will be tested to restore nerve function and recover skin sensation.

Loss of skin sensitivity after breast reconstruction can greatly affect the quality of life of women. Yet, the reasons behind this sensory loss are not well understood. SkinSense aims to uncover the biological causes of this dysfunction and test ways to restore sensation. This research could lead to new treatments that improve sensory outcomes for patients undergoing reconstructive surgery.