@phdthesis{Geyer2016, author = {Geyer, Juliane}, title = {Adapting biodiversity conservation management to climate change}, school = {Universit{\"a}t Potsdam}, pages = {198}, year = {2016}, language = {en} } @phdthesis{Heinze2016, author = {Heinze, Johannes}, title = {The impact of soil microbiota on plant species performance and diversity in semi-natural grasslands}, school = {Universit{\"a}t Potsdam}, pages = {157}, year = {2016}, language = {en} } @phdthesis{Reichel2016, author = {Reichel, Victoria Eleonore}, title = {Biomedical applications and multifunctional nanostructures based on magnetite nanoparticles synthesized in presence of biological additives}, school = {Universit{\"a}t Potsdam}, pages = {94, XX}, year = {2016}, language = {en} } @phdthesis{OnanaEloundouEpseMbebi2016, author = {Onana Eloundou Epse Mbebi, Jeanne Marie}, title = {Robustness and plasticity in chemical reaction networks}, school = {Universit{\"a}t Potsdam}, pages = {116}, year = {2016}, language = {en} } @phdthesis{Fiedler2016, author = {Fiedler, Dorothea}, title = {Impact of Dissolved Organic Nitrogen on Freshwater Phytoplankton}, school = {Universit{\"a}t Potsdam}, pages = {XIII, 92}, year = {2016}, abstract = {In freshwater sciences, nitrogen gained increasing attention in the past as an important resource potentially influencing phytoplankton growth and thus eutrophication. Most studies and all management approaches, however, are still restricted to dissolved inorganic nitrogen (DIN = nitrate + nitrite + ammonium) since dissolved organic nitrogen (DON) was considered to be refractory for most of the photoautotrophs. In the meantime this assumption has been disproved for all aquatic systems. While research on DON in marine ecosystems substantially increased, in freshwater a surprisingly small number of investigations has been carried out on DON utilization by phytoplankton or even the occurrence and seasonal development of total DON or its compounds in lakes. Therefore, our present knowledge on DON utilization by phytoplankton is often based on single species experiments using a sole, usually low molecular weight DON component, often in unnaturally high amounts mainly carried out with marine phytoplankton species. Thus, we know that some phytoplankton species can take up different DON fractions if they are available in high concentrations and as sole nitrogen source. This does not necessarily imply that phytoplankton would perform likewise in natural environments. In addition, it will be difficult to draw conclusions on the behavior of freshwater phytoplankton from experiments with marine phytoplankton since the nutrient regime in marine environments differs from that of freshwater. In the light of the parallel availability of inorganic and organic nitrogen species in natural freshwater ecosystems, several questions must be raised: "If inorganic nitrogen is available, would phytoplankton really rely on an organic nitrogen source? Could a connection be detected between the seasonal development of DON and changes in the phytoplankton community composition as found for inorganic nitrogen? And if we reduce the input of inorganic nitrogen in lakes and rivers would the importance of DON as nitrogen source for phytoplankton increase, counteracting all management efforts or even leading to undesired effects due to changes in phytoplankton physiology and biodiversity?" I experimentally addressed the questions whether those DON compounds differentially influence growth, physiology and composition of phytoplankton both as sole available nitrogen source and in combination with other nitrogen compounds. I hypothesized that all offered DON - compounds (urea, natural organic matter (NOM), dissolved free and combined amino acids (DFAA, DCAA)) could be utilized by phytoplankton at natural concentrations. However, I assumed that the availability would decrease with increasing compound complexity. I furthermore hypothesized that the occurrence of low DIN concentrations would not affect the utilization of DON negatively. The nitrogen source, whatsoever, would have an impact on phytoplankton physiology as well as community composition. To investigate these questions and assumptions I conducted bioassays with algae monocultures as well as phytoplankton communities testing the utilization of various DON compounds by several freshwater phytoplankton species. Especially the potential utilization of NOM, a complex DON compound mainly consisting of humic substances is of interest, since it is usually regarded to be refractory. In order to be able to use natural concentrations of DON - compounds for my experiments the concentration of total DON and some DON - compounds (urea, humic substances, heigh molecular weight substances) was assessed in Lake M{\"u}ggelsee. All compounds were able to support algae growth in the low natural concentrations supplied. However, I found that the offered DON compounds differ in their availability to various algae species, both, as sole nitrogen source or in combination with low DIN concentrations. As expected, the availability decreased with increasing complexity of the nitrogen compound. Furthermore, I could show that changes in algal physiology (nitrogen storage, metabolism) occur depending on the utilized nitrogen source. Especially the secondary photosynthetic pigment composition, heterocyst frequency and C:N - ratio of the algae were affected. The uptake and usage of certain nitrogen compounds might be more costly, potentially resulting in those physiology changes. Whereas laboratory experiments with single species revealed strong effects of DON, algal responses to DON in a multi-species situation remain unclear. Experiments with phytoplankton communities from Lake M{\"u}ggelsee revealed that the nitrogen pool composition does influence the phytoplankton community structure. The findings furthermore show that several species combined might utilize the supplied nitrogen completely different than monocultures in the laboratory. Thus, besides the actual ability of algae to use the offered nitrogen sources other factors, such as interspecific competition, may be of importance. I further investigated, if the results of the laboratory experiments, can be verified in the field. Here, I surveyed the seasonal development of several dissolved organic matter (DOM) components (urea, high molecular weight substances (HMWS), humic substances (HS)) and associated parameters (Specific UV-absorption (SUVA), C:N - ratio) in Lake M{\"u}ggelsee between 2011 and 2013. Furthermore, data from the long term measurements series of Lake M{\"u}ggelsee such as physical (temperature, light, pH, O2) and chemical parameters (nitrogen, phosphorous, silica, inorganic carbon), zooplankton and phytoplankton data were used to investigate how much of the variability of the phytoplankton composition in Lake M{\"u}ggelsee can be explained by DON/DOM concentration and composition, relative to the other groups of explanatory variables. The results show that DON mainly consists of rather complex compounds such as humic substances and biopolymers (80 \%) and that only slight seasonal trends are detectable. Using variance partitioning I could show, that the usually investigated nutrients (DIN, silica, inorganic carbon, phosphorous) and abiotic factors together explain most of the algae composition as was to be expected (57.1 \% of modeled variance). However, DOM and the associated parameters uniquely explain 10.3 \% of the variance and thus slightly more than zooplankton with 9.3 \%. I could therefore prove, that the composition of DOM (nitrogen and carbon) is connected to the algae composition in an eutrophic lake such as Lake M{\"u}ggelsee. DON - compounds such as urea, however, could not be correlated with the occurrence of specific phytoplankton species. Overall, the results of this study imply that DON can be a valuable nitrogen source for freshwater phytoplankton. DON is used by various species even when DIN is available in low concentrations. Through the reduction of DIN in lakes and rivers, the DON:DIN ratio might be changed, resulting even in an increased importance of DON as phytoplankton nitrogen source. My work suggests that not only N2-fixation but also DON utilization might compensate for reduced N - input. Changes from DIN to DON as main nitrogen source might also promote certain, potentially undesired algae species and influence the biodiversity of a limnic ecosystem through changes in the phytoplankton community structure. Thus, DON, especially urea, should be included in calculations concerning total available nitrogen and when determining nitrogen threshold values. Furthermore, the input-reduction of DON, for example from waste-water treatment plants should also be evaluated and the results of my thesis should find consideration when planning to reduce the nitrogen input in freshwater.}, language = {en} } @article{SchmidtRabschBroekeretal.2016, author = {Schmidt, Andreas and Rabsch, Wolfgang and Broeker, Nina K. and Barbirz, Stefanie}, title = {Bacteriophage tailspike protein based assay to monitor phase variable glucosylations in Salmonella O-antigens}, series = {BMC microbiology}, volume = {16}, journal = {BMC microbiology}, publisher = {BioMed Central}, address = {London}, issn = {1471-2180}, doi = {10.1186/s12866-016-0826-0}, pages = {11}, year = {2016}, abstract = {Background Non-typhoid Salmonella Typhimurium (S. Typhimurium) accounts for a high number of registered salmonellosis cases, and O-serotyping is one important tool for monitoring epidemiology and spread of the disease. Moreover, variations in glucosylated O-antigens are related to immunogenicity and spread in the host. However, classical autoagglutination tests combined with the analysis of specific genetic markers cannot always reliably register phase variable glucose modifications expressed on Salmonella O-antigens and additional tools to monitor O-antigen glucosylation phenotypes of S. Typhimurium would be desirable. Results We developed a test for the phase variable O-antigen glucosylation state of S. Typhimurium using the tailspike proteins (TSP) of Salmonella phages 9NA and P22. We used this ELISA like tailspike adsorption (ELITA) assay to analyze a library of 44 Salmonella strains. ELITA was successful in discriminating strains that carried glucose 1-6 linked to the galactose of O-polysaccharide backbone (serotype O1) from non-glucosylated strains. This was shown by O-antigen compositional analyses of the respective strains with mass spectrometry and capillary electrophoresis. The ELITA test worked rapidly in a microtiter plate format and was highly O-antigen specific. Moreover, TSP as probes could also detect glucosylated strains in flow cytometry and distinguish multiphasic cultures differing in their glucosylation state. Conclusions Tailspike proteins contain large binding sites with precisely defined specificities and are therefore promising tools to be included in serotyping procedures as rapid serotyping agents in addition to antibodies. In this study, 9NA and P22TSP as probes could specifically distinguish glucosylation phenotypes of Salmonella on microtiter plate assays and in flow cytometry. This opens the possibility for flow sorting of cell populations for subsequent genetic analyses or for monitoring phase variations during large scale O-antigen preparations necessary for vaccine production.}, language = {en} } @phdthesis{EbrahimianMotlagh2016, author = {Ebrahimian Motlagh, Saghar}, title = {Functional characterization of stress-responsive transcription factors and their gene regulatory networks in Arabidopsis thaliana}, school = {Universit{\"a}t Potsdam}, pages = {155, X}, year = {2016}, language = {en} } @phdthesis{Schoeppler2016, author = {Sch{\"o}ppler, Vanessa}, title = {Material properties of Banksia follicles}, school = {Universit{\"a}t Potsdam}, pages = {119}, year = {2016}, language = {en} } @phdthesis{Pellizzer2016, author = {Pellizzer, Tommaso}, title = {A novel approach to identify plastidic factors for plastome genome incompatibility and evidence for the central involvement of the chloroplast in leaf shaping}, school = {Universit{\"a}t Potsdam}, pages = {136}, year = {2016}, language = {en} } @phdthesis{Sauter2016, author = {Sauter, J{\"o}rg}, title = {The molecular origin of plant cell wall swelling}, school = {Universit{\"a}t Potsdam}, pages = {iii, 127 S.}, year = {2016}, abstract = {In dieser Arbeit werden die Eigenschaften von hydratisierten Hemicellulose Polysacchariden mittels Computersimulation untersucht. Die hohe Quellfähigkeit von Materialien die aus diesen Molek{\"u}len bestehen, erlaubt die Erzeugung von zielgerichteter Bewegung in Planzenmaterialien, ausschließlich gesteuert durch Wasseraufnahme. Um den molekularen Ursprung dieses Quellvermögens zu untersuchen wird, im Vergleich mit Experimenten, ein atomistisches Modell f{\"u}r Hemicellulose Polysaccharide entwickelt und getestet. Unter Verwendung dieses Modells werden Simulationen von kleinen Polysacchariden benutzt um die Wechselwirkungen mit Wasser, den Einfluss von Wasser auf die Konformationsfreiheit der Molek{\"u}le, und die Quellfähigkeit, quantifiziert durch den osmotischen Druck, zu verstehen. Es wird gezeigt, dass verzweigte und lineare Polysaccharide unterschiedliche Hydratisierungseingenschaften im Vergleich zu lineare Polysacchariden aufweisen. Um das Quellverhalten auf Längen- und Zeitskalen untersuchen zu können die {\"u}ber die Begrenzungen atomistischer Simulationen hinausgehen, wurde eine Prozedur entwickelt um {\"u}bertragbare vergröberte Modelle herzuleiten. Die Übertragbarkeit der vegröberten Modelle wird gezeigt, sowohl {\"u}ber unterschiedliche Polysaccharidkonzentrationen als auch {\"u}ber unterschiedliche Polymerlängen. Daher erlaubt die Prozedur die Konstruktion von großen vergröberter Systemen ausgehend von kleinen atomistischen Referenzsystemen. Abschließend wird das vergröberte Modell verwendet um zu zeigen, dass lineare und verzweigte Polysaccharide ein unterschiedliches Quellverhalten aufweisen, wenn sie mit einem Wasserbad gekoppelt werden.}, language = {en} } @phdthesis{Sin2016, author = {Sin, Celine}, title = {Post-transcriptional control of gene expression}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-102469}, school = {Universit{\"a}t Potsdam}, pages = {xxv, 238}, year = {2016}, abstract = {Gene expression describes the process of making functional gene products (e.g. proteins or special RNAs) from instructions encoded in the genetic information (e.g. DNA). This process is heavily regulated, allowing cells to produce the appropriate gene products necessary for cell survival, adapting production as necessary for different cell environments. Gene expression is subject to regulation at several levels, including transcription, mRNA degradation, translation and protein degradation. When intact, this system maintains cell homeostasis, keeping the cell alive and adaptable to different environments. Malfunction in the system can result in disease states and cell death. In this dissertation, we explore several aspects of gene expression control by analyzing data from biological experiments. Most of the work following uses a common mathematical model framework based on Markov chain models to test hypotheses, predict system dynamics or elucidate network topology. Our work lies in the intersection between mathematics and biology and showcases the power of statistical data analysis and math modeling for validation and discovery of biological phenomena.}, language = {en} } @phdthesis{HankeGogokhia2016, author = {Hanke-Gogokhia, Christin}, title = {Small GTPase ARL3-GTP is key molecule in transition zone formation and trafficking of ciliary cargo in mouse photoreceptors}, school = {Universit{\"a}t Potsdam}, pages = {166}, year = {2016}, language = {en} } @phdthesis{Friess2016, author = {Frieß, Fabian}, title = {Shape-memory polymer micronetworks}, school = {Universit{\"a}t Potsdam}, pages = {xiv, 111 S.}, year = {2016}, language = {en} } @phdthesis{Joest2016, author = {J{\"o}st, Jan Moritz Michael}, title = {Broad leaves, narrow leaves or no leaves at all - a genetic and phenotypic dissection of barley leaf size mutants}, school = {Universit{\"a}t Potsdam}, pages = {99}, year = {2016}, language = {en} } @phdthesis{Shikangalah2016, author = {Shikangalah, Rosemary Ndawapeka}, title = {An ecohydrological impact assessment in urban areas}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-102356}, school = {Universit{\"a}t Potsdam}, pages = {ii, 105}, year = {2016}, abstract = {Over the last decades, the world's population has been growing at a faster rate, resulting in increased urbanisation, especially in developing countries. More than half of the global population currently lives in urbanised areas with an increasing tendency. The growth of cities results in a significant loss of vegetation cover, soil compaction and sealing of the soil surface which in turn results in high surface runoff during high-intensity storms and causes the problem of accelerated soil water erosion on streets and building grounds. Accelerated soil water erosion is a serious environmental problem in cities as it gives rise to the contamination of aquatic bodies, reduction of ground water recharge and increase in land degradation, and also results in damages to urban infrastructures, including drainage systems, houses and roads. Understanding the problem of water erosion in urban settings is essential for the sustainable planning and management of cities prone to water erosion. However, in spite of the vast existence of scientific literature on water erosion in rural regions, a concrete understanding of the underlying dynamics of urban erosion still remains inadequate for the urban dryland environments. This study aimed at assessing water erosion and the associated socio-environmental determinants in a typical dryland urban area and used the city of Windhoek, Namibia, as a case study. The study used a multidisciplinary approach to assess the problem of water erosion. This included an in depth literature review on current research approaches and challenges of urban erosion, a field survey method for the quantification of the spatial extent of urban erosion in the dryland city of Windhoek, and face to face interviews by using semi-structured questionnaires to analyse the perceptions of stakeholders on urban erosion. The review revealed that around 64\% of the literatures reviewed were conducted in the developed world, and very few researches were carried out in regions with extreme climate, including dryland regions. Furthermore, the applied methods for erosion quantification and monitoring are not inclusive of urban typical features and they are not specific for urban areas. The reviewed literature also lacked aspects aimed at addressing the issues of climate change and policies regarding erosion in cities. In a field study, the spatial extent and severity of an urban dryland city, Windhoek, was quantified and the results show that nearly 56\% of the city is affected by water erosion showing signs of accelerated erosion in the form of rills and gullies, which occurred mainly in the underdeveloped, informal and semi-formal areas of the city. Factors influencing the extent of erosion in Windhoek included vegetation cover and type, socio-urban factors and to a lesser extent slope estimates. A comparison of an interpolated field survey erosion map with a conventional erosion assessment tool (the Universal Soil Loss Equation) depicted a large deviation in spatial patterns, which underlines the inappropriateness of traditional non-urban erosion tools to urban settings and emphasises the need to develop new erosion assessment and management methods for urban environments. It was concluded that measures for controlling water erosion in the city need to be site-specific as the extent of erosion varied largely across the city. The study also analysed the perceptions and understanding of stakeholders of urban water erosion in Windhoek, by interviewing 41 stakeholders using semi-structured questionnaires. The analysis addressed their understanding of water erosion dynamics, their perceptions with regards to the causes and the seriousness of erosion damages, and their attitudes towards the responsibilities for urban erosion. The results indicated that there is less awareness of the process as a phenomenon, instead there is more awareness of erosion damages and the factors contributing to the damages. About 69\% of the stakeholders considered erosion damages to be ranging from moderate to very serious. However, there were notable disparities between the private householders and public authority groups. The study further found that the stakeholders have no clear understanding of their responsibilities towards the management of the control measures and payment for the damages. The private householders and local authority sectors pointed fingers at each other for the responsibilities for erosion damage payments and for putting up prevention measures. The reluctance to take responsibility could create a predicament for areas affected, specifically in the informal settlements where land management is not carried out by the local authority and land is not owned by the occupants. The study concluded that in order to combat urban erosion, it is crucial to understand diverse dynamics aggravating the process of urbanisation from different scales. Accordingly, the study suggests that there is an urgent need for the development of urban-specific approaches that aim at: (a) incorporating the diverse socio-economic-environmental aspects influencing erosion, (b) scientifically improving natural cycles that influence water storages and nutrients for plants in urbanised dryland areas in order to increase the amount of vegetation cover, (c) making use of high resolution satellite images to improve the adopted methods for assessing urban erosion, (d) developing water erosion policies, and (e) continuously monitoring the impact of erosion and the influencing processes from local, national and international levels.}, language = {en} } @phdthesis{Korkuć2016, author = {Korkuć, Paula}, title = {Spatial investigations of protein structures with regard to compound binding and post-translational modifications}, school = {Universit{\"a}t Potsdam}, pages = {141}, year = {2016}, language = {en} } @phdthesis{Sokolowska2016, author = {Sokolowska, Ewelina Maria}, title = {Implementation of a plasmodesmata gatekeeper system, and its effect on intercellular transport}, school = {Universit{\"a}t Potsdam}, pages = {143}, year = {2016}, language = {en} } @misc{LahTrenseBenkeetal.2016, author = {Lah, Ljerka and Trense, Daronja and Benke, Harald and Berggren, Per and Gunnlaugsson, Þorvaldur and Lockyer, Christina and {\"O}zt{\"u}rk, Ayaka and {\"O}zt{\"u}rk, Bayram and Pawliczka, Iwona and Roos, Anna and Siebert, Ursula and Sk{\´o}ra, Krzysztof and V{\´i}kingsson, G{\´i}sli and Tiedemann, Ralph}, title = {Spatially Explicit Analysis of Genome-Wide SNPs Detects Subtle Population Structure in a Mobile Marine Mammal, the Harbor Porpoise}, issn = {1866-8372}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-100813}, pages = {23 Seiten}, year = {2016}, abstract = {The population structure of the highly mobile marine mammal, the harbor porpoise (Phocoena phocoena), in the Atlantic shelf waters follows a pattern of significant isolation-by-distance. The population structure of harbor porpoises from the Baltic Sea, which is connected with the North Sea through a series of basins separated by shallow underwater ridges, however, is more complex. Here, we investigated the population differentiation of harbor porpoises in European Seas with a special focus on the Baltic Sea and adjacent waters, using a population genomics approach. We used 2872 single nucleotide polymorphisms (SNPs), derived from double digest restriction-site associated DNA sequencing (ddRAD-seq), as well as 13 microsatellite loci and mitochondrial haplotypes for the same set of individuals. Spatial principal components analysis (sPCA), and Bayesian clustering on a subset of SNPs suggest three main groupings at the level of all studied regions: the Black Sea, the North Atlantic, and the Baltic Sea. Furthermore, we observed a distinct separation of the North Sea harbor porpoises from the Baltic Sea populations, and identified splits between porpoise populations within the Baltic Sea. We observed a notable distinction between the Belt Sea and the Inner Baltic Sea sub-regions. Improved delineation of harbor porpoise population assignments for the Baltic based on genomic evidence is important for conservation management of this endangered cetacean in threatened habitats, particularly in the Baltic Sea proper. In addition, we show that SNPs outperform microsatellite markers and demonstrate the utility of RAD-tags from a relatively small, opportunistically sampled cetacean sample set for population diversity and divergence analysis.}, language = {en} } @article{LahTrenseBenkeetal.2016, author = {Lah, Ljerka and Trense, Daronja and Benke, Harald and Berggren, Per and Gunnlaugsson, Þorvaldur and Lockyer, Christina and {\"O}zt{\"u}rk, Ayaka and {\"O}zt{\"u}rk, Bayram and Pawliczka, Iwona and Roos, Anna and Siebert, Ursula and Sk{\´o}ra, Krzysztof and V{\´i}kingsson, G{\´i}sli and Tiedemann, Ralph}, title = {Spatially Explicit Analysis of Genome-Wide SNPs Detects Subtle Population Structure in a Mobile Marine Mammal, the Harbor Porpoise}, series = {PLoS one}, volume = {11}, journal = {PLoS one}, number = {10}, publisher = {PLoS}, address = {Lawrence, Kan.}, issn = {1932-6203}, doi = {10.1371/journal.pone.0162792}, pages = {23 Seiten}, year = {2016}, abstract = {The population structure of the highly mobile marine mammal, the harbor porpoise (Phocoena phocoena), in the Atlantic shelf waters follows a pattern of significant isolation-by-distance. The population structure of harbor porpoises from the Baltic Sea, which is connected with the North Sea through a series of basins separated by shallow underwater ridges, however, is more complex. Here, we investigated the population differentiation of harbor porpoises in European Seas with a special focus on the Baltic Sea and adjacent waters, using a population genomics approach. We used 2872 single nucleotide polymorphisms (SNPs), derived from double digest restriction-site associated DNA sequencing (ddRAD-seq), as well as 13 microsatellite loci and mitochondrial haplotypes for the same set of individuals. Spatial principal components analysis (sPCA), and Bayesian clustering on a subset of SNPs suggest three main groupings at the level of all studied regions: the Black Sea, the North Atlantic, and the Baltic Sea. Furthermore, we observed a distinct separation of the North Sea harbor porpoises from the Baltic Sea populations, and identified splits between porpoise populations within the Baltic Sea. We observed a notable distinction between the Belt Sea and the Inner Baltic Sea sub-regions. Improved delineation of harbor porpoise population assignments for the Baltic based on genomic evidence is important for conservation management of this endangered cetacean in threatened habitats, particularly in the Baltic Sea proper. In addition, we show that SNPs outperform microsatellite markers and demonstrate the utility of RAD-tags from a relatively small, opportunistically sampled cetacean sample set for population diversity and divergence analysis.}, language = {en} } @phdthesis{Gopalakrishnan2016, author = {Gopalakrishnan, Sathej}, title = {Mathematical modelling of host-disease-drug interactions in HIV disease}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-100100}, school = {Universit{\"a}t Potsdam}, pages = {121}, year = {2016}, abstract = {The human immunodeficiency virus (HIV) has resisted nearly three decades of efforts targeting a cure. Sustained suppression of the virus has remained a challenge, mainly due to the remarkable evolutionary adaptation that the virus exhibits by the accumulation of drug-resistant mutations in its genome. Current therapeutic strategies aim at achieving and maintaining a low viral burden and typically involve multiple drugs. The choice of optimal combinations of these drugs is crucial, particularly in the background of treatment failure having occurred previously with certain other drugs. An understanding of the dynamics of viral mutant genotypes aids in the assessment of treatment failure with a certain drug combination, and exploring potential salvage treatment regimens. Mathematical models of viral dynamics have proved invaluable in understanding the viral life cycle and the impact of antiretroviral drugs. However, such models typically use simplified and coarse-grained mutation schemes, that curbs the extent of their application to drug-specific clinical mutation data, in order to assess potential next-line therapies. Statistical models of mutation accumulation have served well in dissecting mechanisms of resistance evolution by reconstructing mutation pathways under different drug-environments. While these models perform well in predicting treatment outcomes by statistical learning, they do not incorporate drug effect mechanistically. Additionally, due to an inherent lack of temporal features in such models, they are less informative on aspects such as predicting mutational abundance at treatment failure. This limits their application in analyzing the pharmacology of antiretroviral drugs, in particular, time-dependent characteristics of HIV therapy such as pharmacokinetics and pharmacodynamics, and also in understanding the impact of drug efficacy on mutation dynamics. In this thesis, we develop an integrated model of in vivo viral dynamics incorporating drug-specific mutation schemes learned from clinical data. Our combined modelling approach enables us to study the dynamics of different mutant genotypes and assess mutational abundance at virological failure. As an application of our model, we estimate in vivo fitness characteristics of viral mutants under different drug environments. Our approach also extends naturally to multiple-drug therapies. Further, we demonstrate the versatility of our model by showing how it can be modified to incorporate recently elucidated mechanisms of drug action including molecules that target host factors. Additionally, we address another important aspect in the clinical management of HIV disease, namely drug pharmacokinetics. It is clear that time-dependent changes in in vivo drug concentration could have an impact on the antiviral effect, and also influence decisions on dosing intervals. We present a framework that provides an integrated understanding of key characteristics of multiple-dosing regimens including drug accumulation ratios and half-lifes, and then explore the impact of drug pharmacokinetics on viral suppression. Finally, parameter identifiability in such nonlinear models of viral dynamics is always a concern, and we investigate techniques that alleviate this issue in our setting.}, language = {en} }