@phdthesis{Cheng2024,
  author    = {Cheng, Feng},
  title     = {Evolution and ontogeny of electric organ discharge in African weakly electric fish genus Campylomormyrus: a genomic and transcriptomic perspective},
  doi       = {10.25932/publishup-63017},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-630172},
  school      = {Universit{\"a}t Potsdam},
  pages     = {176},
  year      = {2024},
  abstract  = {The African weakly electric fishes (Mormyridae) exhibit a remarkable adaptive radiation possibly due to their species-specific electric organ discharges (EODs). It is produced by a muscle-derived electric organ that is located in the caudal peduncle. Divergence in EODs acts as a pre-zygotic isolation mechanism to drive species radiations. However, the mechanism behind the EOD diversification are only partially understood. The aim of this study is to explore the genetic basis of EOD diversification from the gene expression level across Campylomormyrus species/hybrids and ontogeny. I firstly produced a high quality genome of the species C. compressirostris as a valuable resource to understand the electric fish evolution. The next study compared the gene expression pattern between electric organs and skeletal muscles in Campylomormyrus species/hybrids with different types of EOD duration. I identified several candidate genes with an electric organ-specific expression, e.g. KCNA7a, KLF5, KCNJ2, SCN4aa, NDRG3, MEF2. The overall genes expression pattern exhibited a significant association with EOD duration in all analyzed species/hybrids. The expression of several candidate genes, e.g. KCNJ2, KLF5, KCNK6 and KCNQ5, possibly contribute to the regulation of EOD duration in Campylomormyrus due to their increasing or decreasing expression. Several potassium channel genes showed differential expression during ontogeny in species and hybrid with EOD alteration, e.g. KCNJ2. I next explored allele specific expression of intragenus hybrids by crossing the duration EOD species C. compressirostris with the medium duration EOD species C. tshokwe and the elongated duration EOD species C. rhynchophorus. The hybrids exhibited global expression dominance of the C. compressirostris allele in the adult skeletal muscle and electric organ, as well as in the juvenile electric organ. Only the gene KCNJ2 showed dominant expression of the allele from C. rhynchophorus, and this was increasingly dominant during ontogeny. It hence supported our hypothesis that KCNJ2 is a key gene of regulating EOD duration. Our results help us to understand, from a genetic perspective, how gene expression effect the EOD diversification in the African weakly electric fish.},
  language  = {en}
}
@phdthesis{LopesFernando2023,
  author    = {Lopes Fernando, Raquel Sofia},
  title     = {The impact of aging on proteolytic systems, transcriptome and metabolome of slow and fast muscle fiber types},
  doi       = {10.25932/publishup-60579},
  school      = {Universit{\"a}t Potsdam},
  pages     = {XI, 125},
  year      = {2023},
  abstract  = {Aging is a complex process characterized by several factors, including loss of genetic and epigenetic information, accumulation of chronic oxidative stress, protein damage and aggregates and it is becoming an emergent drug target. Therefore, it is the utmost importance to study aging and agerelated diseases, to provide treatments to develop a healthy aging process. Skeletal muscle is one of the earliest tissues affected by age-related changes with progressive loss of muscle mass and function from 30 years old, effect known as sarcopenia. Several studies have shown the accumulation of protein aggregates in different animal models, as well as in humans, suggesting impaired proteostasis, a hallmark of aging, especially regarding degradation systems. Thus, different publications have explored the role of the main proteolytic systems in skeletal muscle from rodents and humans, like ubiquitin proteasomal system (UPS) and autophagy lysosomal system (ALS), however with contradictory results. Yet, most of the published studies are performed in muscles that comprise more than one fiber type, that means, muscles composed by slow and fast fibers. These fiber types, exhibit different metabolism and contraction speed; the slow fibers or type I display an oxidative metabolism, while fast fibers function towards a glycolytic metabolism ranging from fast oxidative to fast glycolytic fibers. To this extent, the aim of this thesis sought to understand on how aging impacts both fiber types not only regarding proteostasis but also at a metabolome and transcriptome network levels. Therefore, the first part of this thesis, presents the differences between slow oxidative (from Soleus muscle) and fast glycolytic fibers (Extensor digitorum longus, EDL) in terms of degradation systems and how they cope with oxidative stress during aging, while the second part explores the differences between young and old EDL muscle transcriptome and metabolome, unraveling molecular features. More specifically, the results from the present work show that slow oxidative muscle performs better at maintaining the function of UPS and ALS during aging than EDL muscle, which is clearly affected, accounting for the decline in the catalytic activity rates and accumulation of autophagy-related proteins. Strinkingly, transcriptome and metabolome analyses reveal that fast glycolytic muscle evidences significant downregulation of mitochondrial related processes and damaged mitochondria morphology during aging, despite of having a lower oxidative metabolism compared to oxidative fibers. Moreover, predictive analyses reveal a negative association between aged EDL gene signature and lifespan extending interventions such as caloric restriction (CR). Although, CR intervention does not alter the levels of mitochondrial markers in aged EDL muscle, it can reverse the higher mRNA levels of muscle damage markers. Together, the results from this thesis give new insights about how different metabolic muscle fibers cope with age-related changes and why fast glycolytic fibers are more susceptible to aging than slow oxidative fibers.},
  language  = {en}
}
@phdthesis{Leer2023,
  author    = {Leer, Marina},
  title     = {Computational analysis of the effects of ageing and diet on stem cell function and ectopic fat accumulation in the musculoskeletal system},
  school      = {Universit{\"a}t Potsdam},
  pages     = {130},
  year      = {2023},
  abstract  = {The musculoskeletal system provides support and enables movement to the body, and its deterioration is a crucial aspect of age-related functional decline. Mesenchymal stromal cells (MSCs) play an important role in musculoskeletal homeostasis due to their broad differentiation potentials and their ability to support osteogenic and myogenic tissue maintenance and regeneration. In the bone, MSCs differentiate either into osteochondrogenic progenitors to form osteocytes and chondrocytes, or increasingly with age into adipogenic progenitors which give rise to bone-resident adipocytes. In skeletal muscle, during healthy regeneration MSCs provide regulatory signals that activate local, tissue-specific stem cells, known as satellite cells, which regenerate contractile myofibres. This process involves a significant cross-talk to immune cells stemming from both lymphoid and myeloid lineages. During ageing, muscle-resident MSCs undergo increased adipogenic lineage commitment, causing niche changes that contribute to fatty infiltration in muscles. These shifts in cell populations in bone lead to the loss of osteogenic cells and subsequently osteoporosis, or in muscle to impaired regeneration and to the development of sarcopenia. However, the signals that drive transition of MSCs into their respective cellular fates remain elusive. This thesis aims to elucidate the transcriptional shifts modulating cell states and cell types in musculoskeletal MSC fate determination. Single-cell RNA-sequencing (scRNA-seq) was used to characterise cell type-specific transcript regulation. State-of-the-art bioinformatics tools were combined with different analytical platforms that include both droplet-based scRNA-seq for large heterogeneous populations, and microfluidics-based scRNA-seq to assess small, rare subpopulations. For each platform, distinct computational pipelines were established including filtering steps to exclude low-quality cells, and data visualisation was performed by dimensionality reduction. Downstream analysis included clustering, cell type annotation, and differential gene expression to investigate transcriptional states in defined cell types during ageing and injury in the muscle and bone. Finally, a novel tool to assess publication activities in defined areas of research for the identified marker genes was developed. The results in the bone indicate that ageing MSCs increasingly commit towards an adipogenic fate at the expense of osteogenic specialisation. The data also suggests that significant cell population shifts of MSC-type fibro-adipogenic progenitors during muscle ageing underlie the pathologies observed in homeostatic and post-injury regenerative conditions. High-throughput visualisation of publication activity for candidate genes enabled more effective biological evaluation of scRNA-seq data. These results expose critical age-related changes in the stem cell niches of skeletal muscle and bone, highlight their respective sensitivity to nutrition and pathology, and elucidate novel factors that modulate stem cell-based regeneration. Targeting these processes might improve musculoskeletal health in the context of ageing and prevent the negative effects of pathological lineage determination.},
  language  = {en}
}
@phdthesis{Makower2016,
  author    = {Makower, Katharina},
  title     = {The roles of secondary metabolites in microcystis inter-strain interactions},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-93916},
  school      = {Universit{\"a}t Potsdam},
  pages     = {X, 131},
  year      = {2016},
  abstract  = {Among the bloom-forming and potentially harmful cyanobacteria, the genus Microcystis represents a most diverse taxon, on the genomic as well as on morphological and secondary metabolite levels. Microcystis communities are composed of a variety of diversified strains. The focus of this study lies on potential interactions between Microcystis representatives and the roles of secondary metabolites in these interaction processes. The role of secondary metabolites functioning as signaling molecules in the investigated interactions is demonstrated exemplary for the prevalent hepatotoxin microcystin. The extracellular and intracellular roles of microcystin are tested in microarray-based transcriptomic approaches. While an extracellular effect of microcystin on Microcystis transcription is confirmed and connected to a specific gene cluster of another secondary metabolite in this study, the intracellularly occurring microcystin is related with several pathways of the primary metabolism. A clear correlation of a microcystin knockout and the SigE-mediated regulation of carbon metabolism is found. According to the acquired transcriptional data, a model is proposed that postulates the regulating effect of microcystin on transcriptional regulators such as the alternative sigma factor SigE, which in return captures an essential role in sugar catabolism and redox-state regulation. For the purpose of simulating community conditions as found in the field, Microcystis colonies are isolated from the eutrophic lakes near Potsdam, Germany and established as stably growing under laboratory conditions. In co-habitation simulations, the recently isolated field strain FS2 is shown to specifically induce nearly immediate aggregation reactions in the axenic lab strain Microcystis aeruginosa PCC 7806. In transcriptional studies via microarrays, the induced expression program in PCC 7806 after aggregation induction is shown to involve the reorganization of cell envelope structures, a highly altered nutrient uptake balance and the reorientation of the aggregating cells to a heterotrophic carbon utilization, e.g. via glycolysis. These transcriptional changes are discussed as mechanisms of niche adaptation and acclimation in order to prevent competition for resources.},
  language  = {en}
}
@phdthesis{Lamanna2015,
  author    = {Lamanna, Francesco},
  title     = {Adaptive radiation and speciation in African weakly-electric fish},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-80097},
  school      = {Universit{\"a}t Potsdam},
  pages     = {114},
  year      = {2015},
  abstract  = {The rise of evolutionary novelties is one of the major drivers of evolutionary diversification. African weakly-electric fishes (Teleostei, Mormyridae) have undergone an outstanding adaptive radiation, putatively owing to their ability to communicate through species-specific Electric Organ Discharges (EODs) produced by a novel, muscle-derived electric organ. Indeed, such EODs might have acted as effective pre-zygotic isolation mechanisms, hence favoring ecological speciation in this group of fishes. Despite the evolutionary importance of this organ, genetic investigations regarding its origin and function have remained limited. The ultimate aim of this study is to better understand the genetic basis of EOD production by exploring the transcriptomic profiles of the electric organ and of its ancestral counterpart, the skeletal muscle, in the genus Campylomormyrus. After having established a set of reference transcriptomes using "Next-Generation Sequencing" (NGS) technologies, I performed in silico analyses of differential expression, in order to identify sets of genes that might be responsible for the functional differences observed between these two kinds of tissues. The results of such analyses indicate that: i) the loss of contractile activity and the decoupling of the excitation-contraction processes are reflected by the down-regulation of the corresponding genes in the electric organ; ii) the metabolic activity of the electric organ might be specialized towards the production and turnover of membrane structures; iii) several ion channels are highly expressed in the electric organ in order to increase excitability, and iv) several myogenic factors might be down-regulated by transcription repressors in the EO. A secondary task of this study is to improve the genus level phylogeny of Campylomormyrus by applying new methods of inference based on the multispecies coalescent model, in order to reduce the conflict among gene trees and to reconstruct a phylogenetic tree as closest as possible to the actual species-tree. By using 1 mitochondrial and 4 nuclear markers, I was able to resolve the phylogenetic relationships among most of the currently described Campylomormyrus species. Additionally, I applied several coalescent-based species delimitation methods, in order to test the hypothesis that putatively cryptic species, which are distinguishable only from their EOD, belong to independently evolving lineages. The results of this analysis were additionally validated by investigating patterns of diversification at 16 microsatellite loci. The results suggest the presence of a new, yet undescribed species of Campylomormyrus.},
  language  = {en}
}
@phdthesis{Reinert2012,
  author    = {Reinert, Armin},
  title     = {Identifizierung und funktionelle Charakterisierung von f{\"u}r die arbuskul{\"a}re Mykorrhizasymbiose spezifischen Genen in Medicago truncatula},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-63805},
  school      = {Universit{\"a}t Potsdam},
  year      = {2012},
  abstract  = {Die Mykorrhiza (griechisch: m{\´y}kēs f{\"u}r „Pilz"; rhiza f{\"u}r „Wurzel") stellt eine Symbiose zwischen Pilzen und einem Großteil der Landpflanzen dar. Der Pilz verbessert durch die Symbiose die Versorgung der Pflanze mit N{\"a}hrstoffen, w{\"a}hrend die Pflanze den Pilz mit Kohlenhydraten versorgt. Die arbuskul{\"a}re Mykorrhiza (AM) stellt dabei einen beson-dere Form der Mykorrhiza dar. Der AM-Pilz bildet dabei w{\"a}hrend der Symbiose die namensgebenden Arbuskeln innerhalb der Wurzelzellen als Ort des prim{\"a}ren N{\"a}hrstoff- austausches aus. Die AM-Symbiose (AMS) ist der Forschungsschwerpunkt dieser Arbeit. Als Modellorganismen wurden Medicago truncatula und Glomus intraradices verwendet. Es wurden Transkriptionsanalysen durchgef{\"u}hrt um u.a. AMS regulierte Transkriptions- faktoren (TFs) zu identifizieren. Die Aktivit{\"a}t der Promotoren von drei der so identifizier-ten AMS-regulierten TFs (MtOFTN, MtNTS, MtDES) wurde mit Hilfe eine Reportergens visualisiert. Der Bereich der gr{\"o}ßten Promotoraktivit{\"a}t waren in einem Fall nur die ar- buskelhaltigen Zellen (MtOFTN). Im zweiten Fall war der Promotor auch aktiv in nicht arbuskelhaltigen Zellen, jedoch am st{\"a}rksten aktiv in den arbuskelhaltigen Zellen (MtNTS). Ein weiterer Promotor war in arbuskelhaltigen Zellen und den diesen benach-barten Zellen gleich aktiv (MtDES). Zus{\"a}tzlich wurden weitere Gene als AMS-reguliert identifiziert und es wurde f{\"u}r drei dieser Gene (MtPPK, MtAmT, MtMDRL) ebenfalls eine Promotor::Reporter-Aktivit{\"a}ts- studie durchgef{\"u}hrt. Die Promotoren der Kinase (MtPPK) und des Ammoniumtrans-porters (MtAmt) waren dabei ausschließlich in arbuskelhaltigen Zellen aktiv, w{\"a}hrend die Aktivit{\"a}t des ABC-Transporters (MtMDRL) keinem bestimmten Zelltyp zuzuordnen war. F{\"u}r zwei weitere identifizierte Gene, ein Kupfertransporter (MtCoT) und ein Zucker- bzw. Inositoltransporter (MtSuT), wurden RNA-Interferenz (RNAi)-Untersuchungen durchgef{\"u}hrt. Dabei stellte sich in beiden F{\"a}llen heraus, dass, sobald ein RNAi-Effekt in den transformierten Wurzeln vorlag, diese in einem deutlich geringerem Ausmaß wie in der Wurzelkontrolle von G. intraradices kolonisiert worden sind. Im Falle von MtCoT k{\"o}nnte das aus dem selben Grund geschehen, wie im Falle von MtPt4. Welche Rolle MtSuT genau in der Ausbildung der AMS spielt und welche Rolle Inositol in der Aus- bildung der AMS spielt m{\"u}sste durch weitere Untersuchungen am Protein untersucht werden. Weitere Untersuchen an den in dieser Arbeit als spezifisch f{\"u}r arbuskelhaltige Zellen gezeigten Genen MtAmT, MtPPK und MtOFTN k{\"o}nnten ebenfalls aufschlussreich f{\"u}r das weitere Verst{\"a}ndnis der AMS sein. Dies trifft auch auf die TFs MtNTS und MtDES zu, die zwar nicht ausschließlich arbuskelspezifisch transkribiert werden, aber auch eine Rolle in der Regulation der AMS innerhalb von M. truncatula Wurzeln zu spielen scheinen.},
  language  = {de}
}
@phdthesis{Mutwil2011,
  author    = {Mutwil, Marek},
  title     = {Integrative transcriptomic approaches to analyzing plant co-expression networks},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-50752},
  school      = {Universit{\"a}t Potsdam},
  year      = {2011},
  abstract  = {It is well documented that transcriptionally coordinated genes tend to be functionally related, and that such relationships may be conserved across different species, and even kingdoms. (Ihmels et al., 2004). Such relationships was initially utilized to reveal functional gene modules in yeast and mammals (Ihmels et al., 2004), and to explore orthologous gene functions between different species and kingdoms (Stuart et al., 2003; Bergmann et al., 2004). Model organisms, such as Arabidopsis, are readily used in basic research due to resource availability and relative speed of data acquisition. A major goal is to transfer the acquired knowledge from these model organisms to species that are of greater importance to our society. However, due to large gene families in plants, the identification of functional equivalents of well characterized Arabidopsis genes in other plants is a non-trivial task, which often returns erroneous or inconclusive results. In this thesis, concepts of utilizing co-expression networks to help infer (i) gene function, (ii) organization of biological processes and (iii) knowledge transfer between species are introduced. An often overlooked fact by bioinformaticians is that a bioinformatic method is as useful as its accessibility. Therefore, majority of the work presented in this thesis was directed on developing freely available, user-friendly web-tools accessible for any biologist.},
  language  = {en}
}