Cervical cancer is the fourth most common cancer in women. It is caused by the hu- man papillomavirus (HPV). There are many different types of HPV, some of which are high-risk, highly associated with cancer, and low-risk. While HPV is very common— most sexually active individuals will contract some sexually transmitted HPV infec- tion in their lifetime—most infections are cleared without any complication. However, persistent infections may establish and develop into cancerous lesions. Two vaccines have been developed against the two most high-risk types, and have shown high lev- els of efficacy thus far. However, infections are still occurring and it is not clear why some individuals develop persistent infections while others do not. In this thesis, we develop a model to describe how the infection spreads within the host. We express the basic reproduction number R0, a threshold for the establishment of an infection. We solve for the diseased equilibrium, providing insight about whether an infection will persist or not. We develop a spatial model to examine how spatiality of the infec- tion process affects the establishment or clearance. Lastly, we develop a multi-type HPV model to examine whether competitive HPV types are able to coexist in the host for different levels of competition. Ultimately, this work provides groundwork for within-host modelling of HPV and can provide direction for future research. / Thesis / Master of Science (MSc) / The human papillomavirus (HPV) is a sexually transmitted infection that is known to cause cervical cancer in women along with other genital cancers. Cervical cancer is the fourth most common cancer in women, and thus researchers are looking to reduce the number of cervical cancer cases and the number of HPV infections. In order for HPV to cause cervical cancer, the infection must persist for a long time. Most individuals clear the infection without any complication; however, some individuals develop persistent infections. By using mathematical and computation models, we hope to understand why and how HPV infections spread in the host. We develop a criterion for when the infection may be able to establish in the host, and explore conditions that could lead to clearance. Understanding when and how infections will persist could inform treatment and monitoring of cervical cancer development.

Honey bee colonies all over Europe and North America have been declining dramatically for over three decades and is continuing to do so which is causing significant threats to economy, agriculture and ecosystems. The main reason behind the declining colonies is an ectoparasitic mite known as Varroa destructor and viruses vectored by the mite. In previous studies, it has been suggested that a unique mite-resistant subpopulation of honey bees (Apis mellifera) in Gotland, Sweden have developed adaptive tolerance to these viruses as they have managed to survive high mite infestation through natural selection without any mite control treatment. This indicates that there might be a correlation between resistance to Varroa destructor and virus tolerance. This project examined if a correlation between virus resistance and/or virus tolerance can be observed in Varroa-resistant honey bees from unique subpopulations in Europe covering Sweden, Norway, France and Netherlands. Results showed that no correlation could be established based on the findings in this project. However, significant differences in winter colony survival numbers between mite-resistant and mite-susceptible honey bees suggest that tolerance mechanisms could be present in these subpopulations. Further studies are required to verify this hypothesis.

Knowledge about structure and dynamics of the important biological macromolecules — proteins, nucleic acids, lipids and sugars — helps to understand their function. Atomic-resolution structures of macromolecules are routinely captured with X-ray crystallography and other techniques. In this thesis, simulations are used to explore the dynamics of the molecules beyond the static structures. Viruses are machines constructed from macromolecules. Crystal structures of them reveal little to no information about their genomes. In simulations of empty capsids, we observed a correlation between the spatial distribution of chloride ions in the solution and the position of RNA in crystals of satellite tobacco necrosis virus (STNV) and satellite tobacco mosaic virus (STMV). In this manner, structural features of the non-symmetric RNA could also be inferred. The capsid of STNV binds calcium ions on the icosahedral symmetry axes. The release of these ions controls the activation of the virus particle upon infection. Our simulations reproduced the swelling of the capsid upon removal of the ions and we quantified the water permeability of the capsid. The structure and dynamics of the expanded capsid suggest that the disassembly is initiated at the 3-fold symmetry axis. Several experimental methods require biomolecular samples to be injected into vacuum, such as mass-spectrometry and diffractive imaging of single particles. It is therefore important to understand how proteins and molecule-complexes respond to being aerosolized. In simulations we mimicked the dehydration process upon going from solution into the gas phase. We find that two important factors for structural stability of proteins are the temperature and the level of residual hydration. The simulations support experimental claims that membrane proteins can be protected by a lipid micelle and that a non-membrane protein could be stabilized in a reverse micelle in the gas phase. A water-layer around virus particles would impede the signal in diffractive experiments, but our calculations estimate that it should be possible to determine the orientation of the particle in individual images, which is a prerequisite for three-dimensional reconstruction. / BMC B41, 25/5, 9:15