Formation and prevention of ulcer – skin-on-a-chip approach

Sårdannelse i hud er en ofte forekommende hos oppdrettsfisk hvor årsaken er mangeartet. Bakteriekolonisering og huderosjon etter mekanisk håndtering av fisk er kanskje hovedårsaken til sårdannelse. I prosjektet (ULCER) skal utvikle in vitro system (celler) og ex vivo system ("hud-på-en-chip") for å studere premisser for sårdannelsen, samt studere sårhelingsprosesser. ULCER skal undersøke hvordan temperatur, bakterier og stimulanter påvirker migrasjonshastighet av hudceller - da en vet at hudcellenes (epitelceller) migrasjonshastighet er viktig for sårheling. Om stimulanter (agonister) kan påvirke denne hastigheten vet man ikke noe om enda. Migrasjonshastigheten og mønstre skal undersøkes blant annet ved hjelp av avansert mikroskopi og KI, og fysiologiske prosesser skal dokumenteres ved hjelp av RNA sekvensering. ULCER vil øke forståelsen av hvilke cellulære mekanismer som er viktige under sårdannelse- og heling.

Given the high incidence and occurrence of skin ulcers in Norwegian salmon aquaculture, the fish welfare is compromised. At the same time, the fish producers´ and subcontractors´ economic viability is under distress, and the public perception is lowered which impair the reputation of the industry. ULCER will strengthen the fish biological model and the required technological foundation by developing in vitro (cell cultures) and ex vivo (organ-on-a-chip) systems to study premises for ulcer formation and prevention, which can be exploited into a larger setting. ULCER will investigate how environmental (e.g., temperature) and modulators influence the migratory speed and activity of epithelial cells, and resilience, that may have a significant impact on the wound healing process of the skin. Impaired wound healing would increase the likelihood for colonization of pathogens with subsequent ulcer formation. ULCER offers a unique opportunity for UiT and Norway to gain an important advantage in developing a coherent research community in fishery sciences by cross-pollinating expertise from cell-biology, fish immunology, omics technology, advanced microscopy, and artificial intelligence. We foresee significant experimental and empirical advancement of science, which lead to a better understanding of wound formation, healing, and resilience – which may have a significant impact on fish health. A skin-on-a-chip platform together with optical microscopy provides morphological features and extraction of cellular level information, while transcriptomics will aid in the examination of whole transcriptome changes across a different biological condition. The multi-modal microscopy and transcriptomics investigation approaches enable investigation from single bacterial cells to heterogenous skin tissue models; and unbiased view of all the coding in a biological system, and how those transcripts change in pathogen invasion/colonization.