A5011616524- Gene Regulatory Network Analysis
- Genomics and Chromatin Dynamics
- Muscle Physiology and Disorders
- RNA Research and Splicing
- Cardiomyopathy and Myosin Studies
- Protein Degradation and Inhibitors
- Neurogenetic and Muscular Disorders Research
- RNA and protein synthesis mechanisms
- 3D Printing in Biomedical Research
- Cell Image Analysis Techniques
- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Viral Infections and Immunology Research
- Microtubule and mitosis dynamics
- Epigenetics and DNA Methylation
- Pluripotent Stem Cells Research
- Molecular Biology Techniques and Applications
- RNA regulation and disease
- CRISPR and Genetic Engineering
- Molecular Communication and Nanonetworks
- Bioinformatics and Genomic Networks
- RNA Interference and Gene Delivery
- CAR-T cell therapy research
- Cancer-related Molecular Pathways
Max Delbrück Center
2018-2024
Harvard University
2020-2024
Center for Systems Biology
2020-2023
Technical University of Darmstadt
2018-2019
Humboldt-Universität zu Berlin
2019
Transcription factors (TFs) control gene expression, often acting synergistically. Classical thermodynamic models offer a biophysical explanation for synergy based on binding cooperativity and regulated recruitment of RNA polymerase. Because transcription requires polymerase to transition through multiple states, recent work suggests that "kinetic synergy" can arise TFs distinct steps the cycle. These types are not mutually exclusive difficult disentangle conceptually experimentally. Here,...
Cardiac protein homeostasis, sarcomere assembly, and integration of titin as the sarcomeric backbone are tightly regulated to facilitate adaptation repair. Very little is known on how >3-MDa synthesized, moved, inserted into sarcomeres, detached, degraded. Here, we generated a bifluorescently labeled knockin mouse simultaneously visualize both ends molecule follow titin's life cycle in vivo. We find mRNA, synthesis degradation compartmentalized toward Z-disk adult, but not embryonic...
Abstract Cellular signaling systems precisely transmit information in the presence of molecular noise while retaining flexibility to accommodate needs individual cells. To understand design principles underlying such versatile signaling, we analyzed response tumor suppressor p53 varying levels DNA damage hundreds cells and observed a switch between distinct modes characterized by isolated pulses sustained oscillations accumulation. Guided dynamic theory show that this requires an excitable...
Discontinuous transcription has been described for different mammalian cell lines and numerous promoters. However, our knowledge of how the activity individual promoters is adjusted by dynamic signaling inputs from factors limited. To address this question, we characterized selected target genes that are regulated pulsatile accumulation tumor suppressor p53 in response to ionizing radiation. We performed time-resolved measurements gene expression at single-cell level smFISH used resulting...
To enable reliable cell fate decisions, mammalian cells need to adjust their responses dynamically changing internal states by rewiring the corresponding signaling networks. Here, we combine time-lapse microscopy of endogenous fluorescent reporters with computational analysis understand at single-cell level how p53-mediated DNA damage response is adjusted during cycle progression. Shape-based clustering revealed that dynamics CDK inhibitor p21 diverges from its transcription factor p53 S...
Three states in one blow: a FRET relay system distinguishes between (i) the absence of RNA target, (ii) presence C → U edited or (iii) unedited target by means ratio measurements.
Abstract For decades, studies have noted that transcription factors (TFs) can behave as either activators or repressors of different target genes. More recently, evidence suggests TFs act on simultaneously in positive and negative ways. Here we use biophysical models gene regulation to define, conceptualize explore these two aspects TF action: “duality”, where be overall both at the level transcriptional response, “coherent incoherent” modes regulation, mechanistically a given an activator...
Abstract Fluorogenic oligonucleotide probes allow mRNA imaging in living cells. A key challenge is the cellular delivery of probes. Most agents, such as cell‐penetrating peptides (CPPs) and pore‐forming proteins, require interactions with membrane. Charges play an important role. To explore influence charge on fluorogenic properties efficiency, we compared peptide nucleic acid (PNA)‐ DNA‐based forced intercalation (FIT) Perhaps counterintuitively, fluorescence signaling by charged DNA FIT...
1 Summary Gene regulation involves synergistic interactions between transcription factors (TFs). Classical thermodynamic models offer a biophysical understanding of synergy based on binding cooperativity and regulated recruitment RNA polymerase. However, requires polymerase to transition through multiple states. Accordingly, recent work has suggested that ”kinetic synergy” can arise TFs differentially regulating distinct steps the cycle. Disentangling both sources been challenging. Here, we...
Abstract Cellular signaling systems precisely transmit information in the presence of molecular noise while retaining flexibility to accommodate needs individual cells. To understand design principles underlying such versatile signaling, we analyzed response tumor suppressor p53 varying levels DNA damage hundreds cells and observed a switch between distinct modes characterized by isolated pulses sustained oscillations accumulation. Guided dynamic theory show that this requires an excitable...
Abstract The giant striated muscle protein titin integrates into the developing sarcomere to form a stable myofilament system that is extended as myocytes fuse. logistics underlying assembly and disassembly have started emerge with possibility follow labeled components. Here, we generated mCherry knock-in at titin’s Z-disk study skeletal development remodeling. We find integration tightly regulated its unexpected mobility facilitating homogenous distribution of after cell fusion – an...
The giant striated muscle protein titin integrates into the developing sarcomere to form a stable myofilament system that is extended as myocytes fuse. logistics underlying assembly and disassembly have started emerge with possibility follow labeled components. Here, we generated mCherry knock-in at titin’s Z-disk study skeletal development remodeling. We find integration tightly regulated its unexpected mobility facilitating homogeneous distribution of after cell fusion – an integral part...
A BSTRACT Discontinuous transcription has been described for different mammalian cell lines and numerous promoters. However, our knowledge of how the activity individual promoters is adjusted by dynamic signaling inputs from factor limited. To address this question, we characterized selected target genes that are regulated pulsatile accumulation tumor suppressor p53 in response to ionizing radiation. We performed time resolved measurements gene expression at single level smFISH used...
Gene regulation involves synergistic interactions between transcription factors (TFs). Classical thermodynamic models offer a biophysical understanding of synergy based on binding cooperativity and regulated recruitment RNA polymerase. However, requires polymerase to transition through multiple states. Accordingly, recent work has suggested that "kinetic synergy" can arise TFs differentially regulating distinct steps the cycle. Disentangling both sources been challenging. Here, we combine...