Kandidaten disputerer for ph.d.-graden i helsevitenskap og vil offentlig forsvare avhandlingen:
“Unraveling nanoscale alterations in liver cell fenestrations — Morphological studies via optical super-resolution microscopy approaches”
Avhandlingen er tilgjengelig her! / The doctoral thesis is available here!
På grunn av koronautbruddet er auditoriet stengt for publikum og disputasen vil bli strømmet . Opptak av disputasen vil være tilgjengelig i en måned.
The defense will be streamed because of the corona outbreak. A recording of the disputation will be available for one month.
Prøveforelesning over oppgitt emne starter kl. 10.15/ The trail lecture starts at 10.15
Tittel/Title: “LSEC fenestrae in health and disease”
Prøveforelesningen strømmes her / The trail lecture will be streamed here
Disputasen starter kl. 12.15 / The defense starts at 12.15
Disputasen strømmes her / The defense will be streamed here
De som ønsker å opponere ex auditorio kan sende e-post til leder av disputasen.
Opponents ex auditorio should sign up to leader of defense by e-mail to:
Populærvitenskapelig sammendrag av avhandlingen/ Summary of the thesis:
Our livers are the largest organ in our bodies, and every minute 30% of our blood flows through them. Our livers have two main purposes. The first is to supply the blood (and thus all of the body’s other organs) with essential proteins, hormones, glucose (between meals) and lipoproteins such as low-density lipoprotein (LDL): cholesterol. The second is to clean the blood by removing old or damaged proteins, medicines, excess glucose and excess cholesterol. Much of this supply to - and removal from - the blood goes via small holes (“fenestrations”) in liver sinusoidal endothelial cells (LSECs). As much as 20% of the LSEC surface is perforated with these fenestrations, and LSEC lines the all blood vessels permeating through the liver. In addition, if all the LSEC from a human liver were laid out flat, they would cover the area of one tennis court. This makes LSEC, with their fenestrations, the largest “filter-cell” system in the body.
These fenestrations are really small and range from 50 to 300 nanometers in diameter in normal healthy (and young) people. However, when we age or have liver disease, the fenestrations become fewer and smaller. This restricts the filtration of material to and from the liver, and this will have consequences for the entire body. For example, medicines are removed from the blood by the liver through fenestrations in a process called detoxification. Young people with healthy livers easily detoxify medicines after the medicines have done their job. However, in older people, detoxification goes more slowly because they have smaller and fewer fenestrations, so medicine dosages safe for young people can be poisonous for older people.
The purpose of this thesis is to develop novel ways to look at fenestrations in LSEC via innovative microscope technologies and find ways to keep fenestrations as we age. Until recently it has been impossible to study LSEC fenestrations with ordinary light microscopes because fenestrations are so small. However, we now have new microscopy “tricks” to see fenestrations in living LSEC, and study how they behave and respond to different treatments in real-time. We have improved on these “tricks” by building our super-resolution (dSTORM: direct stochastic optical reconstruction microscopy) microscope for 10% of the cost of a commercial dSTORM system and used it to study LSEC fenestrations. We published this study with a detailed set of building instructions for the dSTORM microscope that other researchers can use. Using our “home-built” dSTORM, and a new commercial structured illumination microscope (SIM), we studied the effect of various compounds on LSEC fenestrations. These compounds included xanthines (caffeine, theobromine, theophylline and others), medicines such as sildenafil, and oxidized LDL (oxLDL): cholesterol. We found that theobromine and sildenafil increased the size and number of fenestrations on LSEC. We found that oxLDL caused major disruptions in LSEC fenestrations – this compound is found in large amounts in patients with severe heart disease and is clearly damaging for LSEC.
In summary, we customized a cost-efficient microscope to visualize very small filter holes (fenestrations) in liver cells. These holes are crucial for good health, and our studies are assisting us to lead ways to maintain these functional fenestrations during aging and liver disease. These methods have helped to show that theobromine (from dark chocolate) and sildenafil (a.k.a Viagra) appear to be beneficial for LSEC fenestrations in in vitro experiments. These findings are still to be confirmed in vivo in animal models. We also showed that oxidized LDL has very negative in vitro effects on LSEC fenestrations. This would suggest that consuming antioxidants would prevent the formation of oxidized LDL and would contribute to better liver health.
Professor Peter McCourt, Institutt for medisinsk biologi, Det helsevitenskapelige fakultet, UiT Norges arktiske universitet
Professor Karen Kristine Sørensen, Institutt for medisinsk biologi, Det helsevitenskapelige fakultet, UiT Norges arktiske universitet
Forsker Cristina Ionica Øie, Institutt for medisinsk biologi, Det helsevitenskapelige fakultet, UiT Norges arktiske universitet
Professor Balpreet Singh Ahluwalia, Institutt for fysikk og teknologi, Fakultet for naturvitenskap og teknologi, UiT Norges arktiske universitet
Reader Patricia Lalor,College of Medical and Dental Sciences, University of Birmingham Edgbaston Birminghamy, United Kingdom – 1. opponent
PhD Seyed Ali Mousavi, Akershus Universitetssykehus, Norway - 2.opponent
Professor Inigo Martinez, Institutt for klinisk medisin, Det helsevitenskapelige fakultet, UiT Norges arktiske universitet – leder av komité
Disputasleder/ Leader of defense:
Førsteamanuensis Erik Dietrichs, Det helsevitenskapelige fakultet, UiT Norges arktiske universitet