Freshwater planarian Schmidtea mediterranea is an emerging model for studying in vivo gene functions and regulation in native cell niches. The obligate asexual strain of this species reproduces by fission, in which succession of soma occurs without passing through the germline. To achieve this somatic immortality the somatic stem cells need to overcome the end replication problem. Therefore it can be hypothesised that somatic telomere maintenance in asexual S. mediterranea must possess a germ-like property, with which age-related erosions can be adequately repaired. In this PhD project, the telomere repeat unit in S. mediterranea was confirmed to be the vertebrate-like TTAGGG. Attrition of whole body telomere length was found in ageing sexual worms and also in asexual worms which had not gone through recent fission events. Opposite telomere length dynamics were observed in regenerated samples of the two strains, with erosion in the sexuals and reset in the asexuals. The telomere maintenance was found to increase during regeneration in both strains, with a higher level of increase in asexual worms. A homolog of the telomerase reverse transcriptase subunit, Smed_Tert, was identified and characterised in this organism. High level of Smed_Tert expression was seen in germ cells in mature sexual worms and adult stem cells in asexual worms. Knockdown of Smed_Tert expression by RNA interference caused progressive telomere erosion, however effects on cell proliferation and viability have not been observed in knockdown samples. Four alternate splice isoforms of Smed_Tert were identified. The enhanced telomerase activity during regeneration correlates with a proportional increase in the full-length isoform and a decrease in isoforms with a truncated TRBD domain, suggesting a dominant negative regulation of telomerase by alternative splicing. Significant increase in the expression of the full-length isoform was seen in regenerating asexual samples but not in sexual strains, which correlates with their telomere length dynamics. It is hoped that the comparative studies between the sexual and asexual strains can improve our understanding of how soma can evolve to become an effective inheritable unit.

During development, polarity is a common feature of many cell types. One example is the polarisation of whole fields of epithelial cells within the plane of the epithelium, a phenomenon called planar cell polarity (PCP). It is widespread in nature and plays important roles in development and physiology. Prominent examples include the epithelial cells of external structures of insects like the fruit fly Drosophila melanogaster, polarised tissue morphogenesis in vertebrates and sensory hair cells in the vertebrate ear. In this work we focus on the wing and the abdomen of Drosophila, where PCP becomes obvious in the alignment of hairs and bristles. The underlying dynamics are not fully understood yet, but two distinct protein networks centred around the transmembrane proteins Frizzled and Dachsous, respectively, have been shown to play essential roles. We will present and analyse five models for different aspects of the process of planar cell polarisation. The first two models assess the nature of PCP in a generic setting, ensuring that the results are valid for whole classes of PCP models. Models three and four are existing more complex models that include detailed assumptions about the underlying protein interactions of the Frizzled system in the Drosophila wing. Model five considers the Dachsous system in the Drosophila abdomen. We describe the features of the different types of mechanisms and determine the conditions under which they can yield polarity. All five models can establish wild-type polarity for a wide range of parameter values. We find, however, that for model one, three and four an inhomogeneous pattern exists for the same parameter values as the polarised state. Therefore, in these cases either specific initial conditions, which are unlikely in nature, or a global bias are necessary to ensure correct polarisation. Furthermore, we present the effects of clonal clusters of cells on the polarity of the surrounding cells in our models and relate them to the phenotypes observed in experiments. Model one and five show the largest discrepance between the numerical and the experimental results. We discuss the biological relevance of these findings and indicate outstanding questions.

The seaweed fly, Coelopa frigida, lives in piles of rotting seaweed deposited on beaches by tides and winds. In all populations studied it is polymorphic for two gene arrangements on Chromosome I. A polymorphism at the alcohol dehydrogenase locus is strongly associated with this inversion and can be used to estimate karyotype frequencies. An extensive series of samples from natural populations has revealed a seasonal cycle in inversion frequencies but otherwise frequencies are remarkably constant both geographically and temporally. There is a consistent excess of heterokaryotypes in these samples. Three selective forces influencing inversion frequencies have been investigated. 1) An association between karyotype and development time, previously observed in the laboratory, has been demonstrated in conditions case to those in natural populations. 2) Viability differences between karyotypes have been examined. In natural populations there is some evidence that the excess of heterokaryotypes increases with larval density. In the laboratory heterokaryotypes are shown to have higher viability than either homokaryotype but the strong density dependence reported previously has not been observed. Viability differences are concentrated in the first two days of larval life and are probably related to the rate of supply of nutrients. 3) An association is demonstrated between karyotype and adult size - especially in males. Adult size is shown to correlate with longevity and fecundity of both sexes. Several experiments indicate that large males enjoy greater mating success than small males. The relationship between larval density, development time and adult size is described. The possibility that the effect of the inversion varies between populations or between alcohol dehydrogenase genotypes has also been investigated. A simulation has been used to study how these selective forces interact with one another, and with the changeable environment in which the flies live, and to examine the extent to which they can account for the observed karyotype frequencies.