Theoretical studies of Membrane Proteins : Properties, Prediction Methods and Genome-wide analysis

Membrane proteins are a large and important class of proteins. They are responsible for several of the key functions in a living cell, e.g. transport of nutrients and ions, cell-cell signaling, and cell-cell adhesion. Despite their importance it has not been possible to study their structure and organization in much detail because of the difficulty to obtain 3D structures. In this thesis theoretical studies of membrane protein sequences and structures have been carried out by analyzing existing experimental data. The data comes from several sources including sequence databases, genome sequencing projects, and 3D structures. Prediction of the membrane spanning regions by hydrophobicity analysis is a key technique used in several of the studies. A novel method for this is also presented and compared to other methods. The primary questions addressed in the thesis are: What properties are common to all membrane proteins? What is the overall architecture of a membrane protein? What properties govern the integration into the membrane? How many membrane proteins are there and how are they distributed in different organisms? Several of the findings have now been backed up by experiments. An analysis of the large family of G-protein coupled receptors pinpoints differences in length and amino acid composition of loops between proteins with and without a signal peptide and also differences between extra- and intracellular loops. Known 3D structures of membrane proteins have been studied in terms of hydrophobicity, distribution of secondary structure and amino acid types, position specific residue variability, and differences between loops and membrane spanning regions. An analysis of several fully and partially sequenced genomes from eukaryotes, prokaryotes, and archaea has been carried out. Several differences in the membrane protein content between organisms were found, the most important being the total number of membrane proteins and the distribution of membrane proteins with a given number of transmembrane segments. Of the properties that were found to be similar in all organisms, the most obvious is the bias in the distribution of positive charges between the extra- and intracellular loops. Finally, an analysis of homologues to membrane proteins with known topology uncovered two related, multi-spanning proteins with opposite predicted orientations. The predicted topologies were verified experimentally, providing a first example of "divergent topology evolution".

Digital Figurations : The Human Figure as Cinematic Concept

Mainstream cinema is to an ever-increasing degree deploying digital imaging technologies to work with the human form; expanding on it, morphing its features, or providing new ways of presenting it. This has prompted theories of simulation and virtualisation to explore the cultural and aesthetic implications, anxieties, and possibilities of a loss of the ‘real’ – in turn often defined in terms of the photographic trace. This thesis wants to provide another perspective. Following instead some recent imperatives in art-theory, this study looks to introduce and expand on the notion of the human figure, as pertaining to processes of figuration rather than (only) representation. The notion of the figure and figuration have an extended history in the fields of hermeneutics, aesthetics, and philosophy, through which they have come to stand for particular theories and methodologies with regards to images and their communication of meaning. This objective of this study is to appropriate these for film-theory, culminating in two case-studies to demonstrate how formal parameters present and organise ideas of the body and the human. The aim is to develop a material approach to contemporary digital practices, where bodies have not ceased to matter but are framed in new ways by new technologies.