Transcriptome

Rett Syndrome (RTT) is a severe neurodevelopmental disorder primarily affecting females. The disease is mainly caused by pathogenic variants in the X-linked MECP2 gene, which encodes for the global transcriptional regulator MeCP2, important for neuronal maturation and maintenance. So far, no cure is currently available. Recently, cell penetrating peptides (CPPs) attracted a special interest in the use of protein replacement therapy by facilitating the transport of proteins across cell membranes and the blood-brain barrier (BBB).In this study, we generated a neuronal cell model by direct reprog

Almost daily we face stressful situations and the body reacts with various coping mechanisms. Consequently, glucocorticoids are released, leading to immunosuppression and a changed metabolism. However, if the stress becomes chronic, the coping systems can be maladaptively altered. In addition, glucocorticoid levels follow a daily circadian rhythm with a peak in the morning just before the organism starts to become active. While it is known that chronic stress can lead to a disruption of the circadian rhythm, it is still not fully understood how the long-term effects after chronic stress and th

Metabolism actively interacts with the proteome, transcriptome, and genome, thereby influencing all facets of biological information and providing cells the adaptability required for optimal functioning across time and space. Neurodevelopment, in particular, depends on the timely integration of numerous molecular signals across cell types, thus deeply relying on metabolite signaling functions. Although measuring changes in metabolites is useful to describe the association between molecules and disorders, the molecular mechanisms through which these metabolites affect neurodevelopment remain un

To investigate gene x environment interactions in a mouse model of cognitive deficits, we examined the impact of mild stress in mice genetically modified to express deficient levels of glutamate dehydrogenase 1 (GDH). GDH (gene name: Glud1) plays a central role in glutamate metabolism and is downregulated in the hippocampus of patients with schizophrenia. Mice with a full deletion of Glud1 in CNS (C-Glud1-/- mice) previously showed abnormally high glutamate levels and a wide range of behavioral deficits. Here, we exposed heterozygous C-Glud1+/- mice and their C-Cre+ controls to mild stress in

The striking diversity of cells in the mammalian brain lies in stark contrast with the uniformity of cells in theoretical models and artificial networks. What computational advantage do these myriad cell types provide? Deciphering their roles first requires organizing cells in the appropriate manner. Typically, cells are organized into a hierarchical clustering of cells into cell types. This approach is based on a rich history of cell typing based on morphology and other accessible correlates. However, the very large-scale datasets enabled by advances in DNA sequencing potentially may reveal a

…Here, we ask if this link between transcriptome and state-dependent processing is a general principle that extends across layers, areas, and species. To this end, we analysed

The cerebral cortex is the most evolved structure of the brain and the site for higher cognitive functions. It consists of 6 layers, each composed of specific types of neurons. Interconnectivity between cortical areas is critical for sensory integration and sensorimotor transformation. Inter-areal cortical projection neurons are located in all cortical layers and form a heterogeneous population, which send their axon across cortical areas, both within and across hemispheres. How this diversity emerges during development remains largely unknown. Here, we address this question by linking the con

…work on peripheral 24-h rhythms on the transcriptome and metabolome in humans, presenting findings from both controlled laboratory studies and field studies. Furthermore, I will highlight the importance of taking into account interindividual differences in the response to circadian misalignment.

Animals traversing different environments encounter both stable background stimuli and novel cues, which are generally thought to be detected by primary sensory neurons and then distinguished by downstream brain circuits. Sensory adaptation is a neural mechanism that filters background by minimizing responses to stable sensory stimuli, and a fundamental feature of sensory systems. Adaptation over relatively fast timescales (milliseconds to minutes) have been reported in many sensory systems. However, adaptation to persistent environmental stimuli over longer timescales (hours to days) have bee

…genome (e.g., de novo mutations), transcriptome, and 3D genome structure lead to debilitating neurodevelopmental disorders, such as autism and schizophrenia. However, current technologies and data are severely limited: (1) 3D genome structures of single brain cells have not been solved; (2) little is known about the dynamics of single-cell transcriptome and 3D genome after birth; (3) true de nov

Ten of thousands of open reading frames (ORFs) are hidden within transcripts. They have eluded annotations because they are either small or within unsuspected locations. These are named alternative ORFs (altORFs) or small ORFs and have recently been highlighted by innovative proteogenomic approaches, such as our OpenProt resource, revealing their existence and implications in biological functions. Due to the absence of altORFs from annotations, pathogenic mutations within these are being ignored. I will discuss our latest progress on the re-analysis of large-scale proteomics datasets to improv

…Slide-seq, a technology which enables transcriptome-wide measurements with near-single cell spatial resolution. We’ll describe recent experimental and computational advances to enable Slide-seq in biological contexts in biological contexts where high detection sensitivity is important. More broadly, we’ll discuss the promise and challenges of spatial transcriptomics for tissue genomics. Lastly, we’ll touch upon novel molecular recording tech

…demands at synapses, identifying the transcriptome and transla