Disputas - Cand. med.vet Ingelin Kyrrestad

Avhendlingen er tilgjengelig her 

The doctoral thesis

Prøveforelesning “The influence of species and sex on liver biology” starter klokken 1015 og vi bli strømmet

Disputasen starter kl. 1215, og strømmes

Auditoriet er åpent for publikum, men disputasen vil også bli strømmet (lenker over).

Opptak av disputasen vil være tilgjengelig i et døgn.

The auditorium is open to the public. The defense will still be streamed (see links above)

Recordings of the trial lecture and the defense will be available for 24 hours.

Populærvitenskapelig sammendrag av avhandlingen:

The liver is a major organ in the body's defense against blood-borne pathogens. It acts as a filter for the blood and is a central site for immune responses, and a central hub for various metabolic processes. Within the liver, an extensive network of small blood vessels, the hepatic sinusoids, are key sites for the exchange of nutrients and waste products between the blood circulation and the liver parenchyma, supporting immune functions and metabolic processes. The liver sinusoidal endothelial cells form the delicate lining of the hepatic sinusoids, acting as scavenger cells with a remarkable ability to eliminate waste products from the bypassing blood. The systemic circulation also carries pathogens, like viruses, that can be swiftly taken up by the LSECs, potentially causing infection in these cells. Cytomegaloviruses targets endothelial cells, but the route of uptake and infection in LSECs has not been described. This thesis aims to provide novel knowledge about the mechanisms of how a pathogenic virus enter and mediates infection in LSECs, and how dexamethasone, an immunosuppressive drug, can affect this.

In the first part of the study, we established a protocol to study virus uptake in mouse LSECs by blocking endocytosis function of the cells. For this purpose, we used dynamin-inhibitors and acidification inhibitor, and evaluated the effect of these. Then, we used this method to study the in vitro uptake and infection by cytomegalovirus, a pathogen highly associated with the liver. Also, we aimed to identify a cell surface receptor able to mediate this infection.

The second part of the study provides a comprehensive overview of biological processes and pathways in LSECs affected by dexamethasone, a frequently used anti-inflammatory and immunosuppressive drug. This was investigated by quantitative proteomics, with the observation that dexamethasone suppressed LSEC activation and inflammation and enhanced the survival of cultured cells.

Lastly, we aimed to find if dexamethasone could affect the susceptibility to cytomegalovirus infection in LSECs and the inflammatory response mediated by the cells. In this study, we investigated LSECs isolated from two different mice strains, BALB/c and C57BL/6, as their immune system can respond differently to viral infections. This study aimed to provide insights into how immunosuppressive drugs can affect virus infection in LSECs, and potential differences caused by genetic background of the mice.

Hovedveileder

Professor Karen Kristine Sørensen, Institutt for medisinsk biologi, UiT Norges arktiske universitet

Biveiledere

Professor emeritus Bård Smedsrød, Institutt for medisinsk biologi, UiT Norges arktiske universitet

Førsteamanuensis Anett Kristin Larsen, Institutt for medisinsk biologi, UiT Norges arktiske universitet

Førsteamanuensis Erik Sveberg Dietrichsen, Institutt for medisinsk biologi, UiT Norges arktiske universitet

Bedømmelseskomité

Professor Victoria Cogger, Sydney University / ANZAC Research Insitute, Concord Hospital – 1. opponent

Associate Professor Lynn Butler, IKM / Karolinska Institutet – 2.opponent

Professor Ellen Aasum, Institutt for medisinsk biologi, Det helsevitenskapelige fakultet, UiT– leder av komité.

Disputasleder: Professor Johanna U. Ericson, UiT Norges arktiske universitet

De som ønsker å opponere ex. auditorio kan sende e-post til leder av disputas Johanna U Ericson (johanna.e.sollid@uit.no) innen kl. 11.00 disputasdagen.