A5058290433- vaccines and immunoinformatics approaches
- Ubiquitin and proteasome pathways
- Immunotherapy and Immune Responses
- Peptidase Inhibition and Analysis
- Gene Regulatory Network Analysis
- T-cell and B-cell Immunology
- Glycosylation and Glycoproteins Research
- Microbial Metabolic Engineering and Bioproduction
- Markov Chains and Monte Carlo Methods
- Influenza Virus Research Studies
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Immune Response and Inflammation
- Advanced Proteomics Techniques and Applications
- Endoplasmic Reticulum Stress and Disease
- RNA and protein synthesis mechanisms
- Diffusion and Search Dynamics
- Single-cell and spatial transcriptomics
- Reproductive Biology and Fertility
- CAR-T cell therapy research
- Advanced Fluorescence Microscopy Techniques
- Hematopoietic Stem Cell Transplantation
- Galectins and Cancer Biology
- Bioinformatics and Genomic Networks
- Zebrafish Biomedical Research Applications
Max Planck Institute for Multidisciplinary Sciences
2022-2024
Quantitative BioSciences
2023
Max Planck Institute for Biophysical Chemistry
2016-2022
Imperial College London
2010-2019
Max Planck Society
2018
London Institute for Mathematical Sciences
2011
Charité - Universitätsmedizin Berlin
2010
New players in the repertoire Antigen-presenting cells, such as macrophages and dendritic activate immunological T cells by presenting them with antigens bound major histocompatibility complexes (MHCs). The proteasome typically processes these antigens, which include peptides derived from both self microbial origins. Liepe et al. now report that, surprisingly, a large fraction of to class I MHC on multiple human cell types are spliced together two different fragments same protein. Such...
Mammalian oocytes are filled with poorly understood structures called cytoplasmic lattices. First discovered in the 1960s and speculated to correspond mammalian yolk, ribosomal arrays, or intermediate filaments, their function has remained enigmatic date. Here, we show that lattices sites where store essential proteins for early embryonic development. Using super-resolution light microscopy cryoelectron tomography, composed of filaments a high surface area, which contain PADI6 subcortical...
Our understanding of most biological systems is in its infancy. Learning their structure and intricacies fraught with challenges, often side-stepped favour studying the function different gene products isolation from physiological context. Constructing inferring global mathematical models experimental data is, however, central to biology. Different setups provide insights into such systems. Here we show how can combine concepts Bayesian inference information theory order identify experiments...
The growing field of systems biology has driven demand for flexible tools to model and simulate biological systems. Two established problems in the modeling processes are selection estimation associated parameters. A number statistical approaches, both frequentist Bayesian, have been proposed answer these questions.Here we present a Python package, ABC-SysBio, that implements parameter inference dynamical an approximate Bayesian computation (ABC) framework. ABC-SysBio combines three...
Immunoproteasomes are considered to be optimised process Ags and alter the peptide repertoire by generating a qualitatively different set of MHC class I epitopes. Whether immunoproteasome at biochemical level, influence quality rather than quantity immuno‐genic pool is still unclear. Here, we quantified cleavage‐site usage human standard‐ immunoproteasomes, proteasomes from immuno‐subunit‐deficient mice, as well peptides generated model polypeptides. We show in this study that proteasome...
Abstract Women are born with all of their oocytes. The oocyte proteome must be maintained minimal damage throughout the woman’s reproductive life, and hence for decades. Here we report that ovarian proteostasis involves extreme protein longevity. Mouse ovaries had more extremely long-lived proteins than other tissues, including brain. These diverse functions, in mitochondria, cytoskeleton, chromatin proteostasis. stable resided not only oocytes but also somatic cells. Our data suggest...
Abstract If and how proteasomes catalyze not only peptide hydrolysis but also splicing is an open question that has divided the scientific community. The debate so far been based on immunopeptidomics, in vitro digestions of synthetic polypeptides as well ex vivo experiments, which could indirectly describe proteasome-catalyzed full-length proteins. Here we develop a workflow—and cognate software - to analyze proteasome-generated non-spliced spliced peptides produced from entire proteins...
Abstract Mitochondria contain dedicated ribosomes (mitoribosomes), which synthesize the mitochondrial-encoded core components of oxidative phosphorylation complexes. The RNA and protein mitoribosomes are encoded on two different genomes (mitochondrial nuclear) assembled into functional complexes with help factors inside organelle. Defects in mitoribosome biogenesis associated severe human diseases, yet molecular pathway assembly remains poorly understood. Here, we applied a multidisciplinary...
Mathematical modelling is central to systems and synthetic biology. Using simulations calculate statistics or explore parameter space a common means for analysing these models can be computationally intensive. However, in many cases, the are easily parallelizable. Graphics processing units (GPUs) capable of efficiently running highly parallel programs outperform CPUs terms raw computing power. Despite their computational advantages, adoption by biology community relatively slow, since...
Anticancer immunotherapies demand optimal epitope targets, which could include proteasome-generated spliced peptides if tumor cells were to present them. Here, we show that are widely presented by MHC class I molecules of colon and breast carcinoma cell lines. The derive from hot spots within antigens enlarge the antigen coverage. Spliced also represent a large number would otherwise be neglected patrolling T cells. These tend long, hydrophobic, basic. Thus, can key identifying targets in an...
In the acute inflammatory phase following tissue damage, cells of innate immune system are rapidly recruited to sites injury by pro-inflammatory mediators released at wound site. Although advances in live imaging allow us directly visualize this process vivo, precise identity and properties primary damage attractants remain unclear, as it is currently impossible observe accurately measure these signals tissues. Here, we demonstrate that detailed information about attractant can be extracted...
Targeting CD8+ T cells to recurrent tumor-specific mutations can profoundly contribute cancer treatment. Some of these are potential tumor antigens although they be displayed by non-spliced epitopes only in a few patients, because the low affinity mutated peptides for predominant HLA class I alleles. Here, we describe pipeline that uses large sequence variety proteasome-generated spliced and identifies epitope candidates, which carry binds HLA-I alleles with high affinity. They could used...
The identification of proteasome-generated spliced peptides (PSP) revealed a new unpredicted activity the major cellular protease. However, so far characterization PSP was entirely dependent on availability patient-derived cytotoxic CD8+ T lymphocytes (CTL) thus preventing systematic investigation proteasome-catalyzed peptide splicing (PCPS). For an unrestricted we here developed SpliceMet, combining computer-based algorithm ProteaJ with in vitro proteasomal degradation assays and mass...
Proteasomal protein degradation is a key determinant of half-life and hence cellular processes ranging from basic metabolism to host immunological processes. Despite its importance the mechanisms regulating proteasome activity are only incompletely understood. Here we use an iterative tightly integrated experimental modelling approach develop, explore validate mechanistic models proteasomal peptide-hydrolysis dynamics. The 20S dynamic enzyme varies over time because interactions between...
CD8(+) T cells responding to infection recognize pathogen-derived epitopes presented by MHC class-I molecules. While most of such are generated proteasome-mediated antigen cleavage, analysis tumor processing has revealed that may also derive from proteasome-catalyzed peptide splicing (PCPS). To determine whether PCPS contributes epitope during infection, we analyzed the fragments produced purified proteasomes a Listeria monocytogenes polypeptide. Mass spectrometry identified known H-2K(b)...
Abstract Osteopontin is a pleiotropic cytokine that involved in several diseases including multiple sclerosis. Secreted osteopontin cleaved by few known proteases, modulating its pro-inflammatory activities. Here we show vitro experiments secreted can be processed extracellular proteasomes, thereby producing fragments with novel chemotactic activity. Furthermore, reduces the release of proteasomes space. The latter phenomenon seems to occur vivo sclerosis, where it reflects remission/relapse...
Abstract Proteasomes are the main producers of antigenic peptides presented to CD8 + T cells. They can cut proteins and release their fragments or recombine non-contiguous thereby generating novel sequences, i.e . spliced peptides. Understanding which driving forces sequence preferences both reactions streamline target discovery in immunotherapies against cancer, infection autoimmunity. Here, we present a large database non-spliced generated by proteasomes vitro , is available as simple CSV...
Here, we develop PEPSeek, a web-server based software to allow higher performance in the identification of pathogen-derived epitope candidates detected via mass spectrometry MHC class I immunopeptidomes. We apply it human and mouse cell lines infected with either SARS-CoV-2, Listeria monocytogenes or Chlamydia trachomatis, thereby identifying large number novel antigens epitopes that prove be recognized by CD8+ T cells. In cells, identified antigenic peptide features suggested how processing...
Journal Article Calibrating spatio-temporal models of leukocyte dynamics against in vivo live-imaging data using approximate Bayesian computation Get access Juliane Liepe, Liepe Centre for Integrative Systems Biology and Bioinformatics, Division Molecular Biosciences, Department Life Sciences, Imperial College London, UK Search other works by this author on: Oxford Academic Google Scholar Harriet Taylor, Taylor Cell Biology, UKMRC Inflammation Research, Queens Medical Research Institute,...