Katharina Gapp

Last Name

Gapp

First Name

Katharina

ORCID

0000-0002-9622-1478

Organisational unit

09783 - Gapp, Katharina / Gapp, Katharina

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Publications 1 - 10 of 27

Socially transferred materials: why and how to study them
Hakala, Sanja Maria; Fujioka, Haruna; Gapp, Katharina; et al. (2023)
Trends in Ecology & Evolution
When biological material is transferred from one individual’s body to another, as in ejaculate, eggs, and milk, secondary donor-produced molecules are often transferred along with the main cargo, and influence the physiology and fitness of the receiver. Both social and solitary animals exhibit such social transfers at certain life stages. The secondary, bioactive, and transfer-supporting components in socially transferred materials have evolved convergently to the point where they are used in applications across taxa and type of transfer. The composition of these materials is typically highly dynamic and context dependent, and their components drive the physiological and behavioral evolution of many taxa. Our establishment of the concept of socially transferred materials unifies this multidisciplinary topic and will benefit both theory and applications.
Deciphering the RNA universe in sperm in its role as a vertical information carrier
Kretschmer, Miriam; Gapp, Katharina (2022)
Environmental Epigenetics
The inheritance of neurophysiologic and neuropsychologic complex diseases can only partly be explained by the Mendelian concept of genetic inheritance. Previous research showed that both psychological disorders like post-traumatic stress disorder and metabolic diseases are more prevalent in the progeny of affected parents. This could suggest an epigenetic mode of transmission. Human studies give first insight into the scope of intergenerational influence of stressors but are limited in exploring the underlying mechanisms. Animal models have elucidated the mechanistic underpinnings of epigenetic transmission. In this review, we summarize progress on the mechanisms of paternal intergenerational transmission by means of sperm RNA in mouse models. We discuss relevant details for the modelling of RNA-mediated transmission, point towards currently unanswered questions and propose experimental considerations for tackling these questions.
Brain metabolic alterations in mice subjected to postnatal traumatic stress and in their offspring
Gapp, Katharina; Corcoba, Alberto; van Steenwyk, Gretchen; et al. (2017)
Journal of Cerebral Blood Flow & Metabolism
Multiomic profiling of the acute stress response in the mouse hippocampus
von Ziegler, Lukas M.; Floriou Servou, Amalia; Waag, Rebecca; et al. (2022)
Nature Communications
The acute stress response mobilizes energy to meet situational demands and re-establish homeostasis. However, the underlying molecular cascades are unclear. Here, we use a brief swim exposure to trigger an acute stress response in mice, which transiently increases anxiety, without leading to lasting maladaptive changes. Using multiomic profiling, such as proteomics, phospho-proteomics, bulk mRNA-, single-nuclei mRNA-, small RNA-, and TRAP-sequencing, we characterize the acute stress-induced molecular events in the mouse hippocampus over time. Our results show the complexity and specificity of the response to acute stress, highlighting both the widespread changes in protein phosphorylation and gene transcription, and tightly regulated protein translation. The observed molecular events resolve efficiently within four hours after initiation of stress. We include an interactive app to explore the data, providing a molecular resource that can help us understand how acute stress impacts brain function in response to stress.
On the identification of differentially-active transcription factors from ATAC-seq data
Gerbaldo, Felix Ezequiel; Sonder, Emanuel; Fischer, Vincent; et al. (2024)
PLoS Computational Biology
ATAC-seq has emerged as a rich epigenome profiling technique, and is commonly used to identify Transcription Factors (TFs) underlying given phenomena. A number of methods can be used to identify differentially-active TFs through the accessibility of their DNA-binding motif, however little is known on the best approaches for doing so. Here we benchmark several such methods using a combination of curated datasets with various forms of short-term perturbations on known TFs, as well as semi-simulations. We include both methods specifically designed for this type of data as well as some that can be repurposed for it. We also investigate variations to these methods, and identify three particularly promising approaches (a chromVAR-limma workflow with critical adjustments, monaLisa and a combination of GC smooth quantile normalization and multivariate modeling). We further investigate the specific use of nucleosome-free fragments, the combination of top methods, and the impact of technical variation. Finally, we illustrate the use of the top methods on a novel dataset to characterize the impact on DNA accessibility of TRAnscription Factor TArgeting Chimeras (TRAFTAC), which can deplete TFs—in our case NFkB—at the protein level.
Single paternal dexamethasone challenge programs offspring metabolism and reveals multiple candidates in RNA-mediated inheritance
Gapp, Katharina; Parada, Guillermo E.; Gross, Fridolin; et al. (2021)
iScience
Single traumatic events that elicit an exaggerated stress response can lead to the development of neuropsychiatric conditions. Rodent studies suggested germline RNA as a mediator of effects of chronic environmental exposures to the progeny. The effects of an acute paternal stress exposure on the germline and their potential consequences on offspring remain to be seen. We find that acute administration of an agonist for the stress-sensitive Glucocorticoid receptor, using the common corticosteroid dexamethasone, affects the RNA payload of mature sperm as soon as 3 hr after exposure. It further impacts early embryonic transcriptional trajectories, as determined by single-embryo sequencing, and metabolism in the offspring. We show persistent regulation of tRNA fragments in sperm and descendant 2-cell embryos, suggesting transmission from sperm to embryo. Lastly, we unravel environmentally induced alterations in sperm circRNAs and their targets in the early embryo, highlighting this class as an additional candidate in RNA-mediated inheritance of disease risk.
Epigenetics of memory and plasticity
Woldemichael, Bisrat T.; Bohacek, Johannes; Gapp, Katharina; et al. (2014)
Progress in Biophysics and Molecular Biology ~ Molecular Basis of Memory
Although all neurons carry the same genetic information, they vary considerably in morphology and functions and respond differently to environmental conditions. Such variability results mostly from differences in gene expression. Among the processes that regulate gene activity, epigenetic mechanisms play a key role and provide an additional layer of complexity to the genome. They allow the dynamic modulation of gene expression in a locus- and cell-specific manner. These mechanisms primarily involve DNA methylation, posttranslational modifications (PTMs) of histones and noncoding RNAs that together remodel chromatin and facilitate or suppress gene expression. Through these mechanisms, the brain gains high plasticity in response to experience and can integrate and store new information to shape future neuronal and behavioral responses. Dynamic epigenetic footprints underlying the plasticity of brain cells and circuits contribute to the persistent impact of life experiences on an individual's behavior and physiology ranging from the formation of long-term memory to the sequelae of traumatic events or of drug addiction. They also contribute to the way lifestyle, life events, or exposure to environmental toxins can predispose an individual to disease. This chapter describes the most prominent examples of epigenetic marks associated with long-lasting changes in the brain induced by experience. It discusses the role of epigenetic processes in behavioral plasticity triggered by environmental experiences. A particular focus is placed on learning and memory where the importance of epigenetic modifications in brain circuits is best understood. The relevance of epigenetics in memory disorders such as dementia and Alzheimer's disease is also addressed, and promising perspectives for potential epigenetic drug treatment discussed.
Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice
Gapp, Katharina; Jawaid, Ali; Sarkies, Peter; et al. (2014)
Nature Neuroscience
Alterations in sperm long RNA contribute to the epigenetic inheritance of the effects of postnatal trauma
Gapp, Katharina; van Steenwyk, Gretchen; Germain, Pierre-Luc; et al. (2020)
Molecular Psychiatry
Psychiatric diseases have a strong heritable component known to not be restricted to DNA sequence-based genetic inheritance alone but to also involve epigenetic factors in germ cells. Initial evidence suggested that sperm RNA is causally linked to the transmission of symptoms induced by traumatic experiences. Here, we show that alterations in long RNA in sperm contribute to the inheritance of specific trauma symptoms. Injection of long RNA fraction from sperm of males exposed to postnatal trauma recapitulates the effects on food intake, glucose response to insulin and risk-taking in adulthood whereas the small RNA fraction alters body weight and behavioural despair. Alterations in long RNA are maintained after fertilization, suggesting a direct link between sperm and embryo RNA.
Epigenetic germline inheritance in mammals: looking to the past to understand the future
Gapp, Katharina; Bohacek, Johannes (2018)
Genes, Brain and Behavior

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Katharina Gapp

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