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".

An evaluation of the distributions of polychlorinated biphenyls and organic matter in coastal sediments

The objective of this thesis is to improve the understanding of what processes and mechanism affects the distribution of polychlorinated biphenyls (PCBs) and organic carbon in coastal sediments. Because of the strong association of hydrophobic organic contaminants (HOCs) such as PCBs with organic matter in the aquatic environment, these two entities are naturally linked. The coastal environment is the most complex and dynamic part of the ocean when it comes to both cycling of organic matter and HOCs. This environment is characterised by the largest fluxes and most diverse sources of both entities. A wide array of methods was used to study these processes throughout this thesis. In the field sites in the Stockholm archipelago of the Baltic proper, bottom sediments and settling particulate matter were retrieved using sediment coring devices and sediment traps from morphometrically and seismically well-characterized locations. In the laboratory, the samples have been analysed for PCBs, stable carbon isotope ratios, carbon-nitrogen atom ratios as well as standard sediment properties. From the fieldwork in the Stockholm Archipelago and the following laboratory work it was concluded that the inner Stockholm archipelago has a low (≈ 4%) trapping efficiency for freshwater-derived organic carbon. The corollary is a large potential for long-range waterborne transport of OC and OC-associated nutrients and hydrophobic organic pollutants from urban Stockholm to more pristine offshore Baltic Sea ecosystems. Theoretical work has been carried out using Geographical Information Systems (GIS) and statistical methods on a database of 4214 individual sediment samples, each with reported individual PCB congener concentrations. From this work it was concluded that the continental shelf sediments are key global inventories and ultimate sinks of PCBs. Depending on congener, 10-80% of the cumulative historical emissions to the environment are accounted for in continental shelf sediments. Further it was concluded that the many infamous and highly contaminated surface sediments of urban harbours and estuaries of contaminated rivers cannot be of importance as a secondary source to sustain the concentrations observed in remote sediments. Of the global shelf PCB inventory < 1% are in sediments near population centres while ≥ 90% is in remote areas (> 10 km from any dwellings). The remote sub-basin of the North Atlantic Ocean contains approximately half of the global shelf sediment inventory for most of the PCBs studied.

On the lifecycle of aerosol particles : Sources and dispersion over Scandinavia

Aerosol particles are likely important contributors to our future climate. Further, during recent years, effects on human health arising from emissions of particulate material have gained increasing attention. In order to quantify the effect of aerosols on both climate and human health we need to better quantify the interplay between sources and sinks of aerosol particle number and mass on large spatial scales. So far long-term, regional observations of aerosol properties have been scarce, but argued necessary in order to bring the knowledge of regional and global distribution of aerosols further. In this context, regional studies of aerosol properties and aerosol dynamics are truly important areas of investigation. This thesis is devoted to investigations of aerosol number size distribution observations performed through the course of one year encompassing observational data from five stations covering an area from southern parts of Sweden up to northern parts of Finland. This thesis tries to give a description of aerosol size distribution dynamics from both a quantitative and qualitative point of view. The thesis focuses on properties and changes in aerosol size distribution as a function of location, season, source area, transport pathways and links to various meteorological conditions. The investigations performed in this thesis show that although the basic behaviour of the aerosol number size distribution in terms of seasonal and diurnal characteristics is similar at all stations in the measurement network, the aerosol over the Nordic countries is characterised by a typically sharp gradient in aerosol number and mass. This gradient is argued to derive from geographical locations of the stations in relation to the dominant sources and transport pathways. It is clear that the source area significantly determine the aerosol size distribution properties, but it is obvious that transport condition in terms of frequency of precipitation and cloudiness in some cases even more strongly control the evolution of the number size distribution. Aerosol dynamic processes under clear sky transport are however likewise argued to be highly important. Southerly transport of marine air and northerly transport of air from continental sources is studied in detail under clear sky conditions by performing a pseudo-Lagrangian box model evaluation of the two type cases. Results from both modelling and observations suggest that nucleation events contribute to integral number increase during southerly transport of comparably clean marine air, while number depletion dominates the evolution of the size distribution during northerly transport. This difference is largely explained by different concentration of pre-existing aerosol surface associated with the two type cases. Mass is found to be accumulated in many of the individual transport cases studied. This mass increase was argued to be controlled by emission of organic compounds from the boreal forest. This puts the boreal forest in a central position for estimates of aerosol forcing on a regional scale.