Thomas Müller-ReichertTechnische Universität Dresden | TUD · Faculty of Medicine Carl Gustav Carus
Thomas Müller-Reichert
Prof. Dr.
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202
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Introduction
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March 2010 - present
March 2010 - May 2019
February 2001 - February 2010
Publications
Publications (202)
Centromeres are scaffolds for the assembly of kinetochores that ensure chromosome segregation during cell division. How vertebrate centromeres obtain a three-dimensional structure to accomplish their primary function is unclear. Using super-resolution imaging, capture-C, and polymer modeling, we show that vertebrate centromeres are partitioned by c...
Modern bioimaging core facilities at research institutions are essential for managing and maintaining high-end instruments, providing training and support for researchers in experimental design, image acquisition and data analysis. An important task for these facilities is the professional management of complex multi-dimensional bioimaging data, wh...
Ribosomes, discovered in 1955 by George Palade, were originally described as small cytoplasmic particles preferentially associated with the endoplasmic reticulum (ER). Over the years, numerous studies were conducted on both ribosome structure and function. The basic question, however, how many ribosomes are contained within whole cells has not been...
Modern bioimaging core facilities at research institutions are essential for managing and maintaining high‐end instruments, providing training and support for researchers in experimental design, image acquisition and data analysis. An important task for these facilities is the professional management of complex multidimensional bioimaging data, whi...
Like other volume electron microscopy approaches, automated tape-collecting ultramicrotomy (ATUM) enables imaging of serial sections deposited on thick plastic tapes by scanning electron microscopy (SEM). ATUM is unique in enabling hierarchical imaging and thus efficient screening for target structures, as needed for correlative light and electron...
Like other volume electron microscopy approaches, Automated Tape Collecting Ultramicrotomy (ATUM) enables imaging of serial sections deposited on thick plastic tapes by scanning electron microscopy (SEM). ATUM is unique in enabling hierarchical imaging and thus efficient screening for target structures, as needed for correlative light and electron...
BACKGROUND
Clinical studies demonstrated beneficial effects of sodium-glucose-transporter 2 inhibitors on the risk of cardiovascular death in patients with heart failure with preserved ejection fraction (HFpEF). However, underlying processes for cardioprotection remain unclear. The present study focused on the impact of empagliflozin (Empa) on myoc...
For the analysis of cellular architecture during mitosis, nanometer resolution is needed to visualize the organization of microtubules in spindles. Here, we present a detailed protocol that can be used to produce 3D reconstructions of whole mitotic spindles in cells grown in culture. For this, we attach mammalian cells enriched in mitotic stages to...
Like other volume electron microscopy approaches, automated tape-collecting ultramicrotomy (ATUM) enables imaging of serial sections deposited on thick plastic tapes by scanning electron microscopy (SEM). ATUM is unique in enabling hierarchical imaging and thus efficient screening for target structures, as needed for correlative light and electron...
Like other volume electron microscopy approaches, Automated Tape Collecting Ultramicrotomy (ATUM) enables imaging of serial sections deposited on thick plastic tapes by scanning electron microscopy (SEM). However, ATUM is unique by enabling hierarchical imaging and thus efficient screening for target structures as needed e.g., for correlated light...
Spermatogenesis leads to the formation of functional sperm cells. Here we have applied high-pressure freezing in combination with transmission electron microscopy (TEM) to study the ultrastructure of sperm development in subadult males of the praying mantid Hierodula membranacea, a species in which spermatogenesis had not previously been studied. W...
Like other volume electron microscopy approaches, Automated Tape Collecting Ultramicrotomy (ATUM) enables imaging of serial sections deposited on thick plastic tapes by scanning electron microscopy (SEM). However, ATUM is unique by enabling hierarchical imaging and thus efficient screening for target structures as needed e.g., for correlated light...
Spermatogenesis leads to the formation of functional sperm cells. Here we have applied high-pressure freezing in combination with transmission electron microscopy (TEM) to study the ultrastructure of sperm development in subadult males of the praying mantid Hierodula membranacea . We show the ultrastructure of different stages of sperm development...
In 1891, the existence of an X chromosome was noted for the first time. Hermann Henking was studying spermatocyte divisions of the firebug Pyrrhocoris apterus and observed that one chromosome behaved differently than all of the rest of the chromosomes. Henking called this chromosome 'Element x'. Henking's discovery of the X element (later called X...
Centrosomes are cellular structures that nucleate microtubules. At their core is a pair of centrioles that recruit pericentriolar material (PCM). Although centrosomes are considered membraneless organelles, in many cell types, including human cells, centrosomes are surrounded by endoplasmic reticulum (ER)-derived membranes of unknown structure and...
Faithful chromosome segregation requires the assembly of a bipolar spindle, consisting of two antiparallel microtubule (MT) arrays having most of their minus ends focused at the spindle poles and their plus ends overlapping in the spindle midzone. Spindle assembly, chromosome alignment and segregation require highly dynamic MTs. The plus ends of MT...
Praying mantids are important models for studying a wide range of chromosome behaviors, yet few species of mantids have been characterized chromosomally. Here we show that the praying mantid Hierodula membranacea has a chromosome number of 2n = 27, and X1X1X2X2 (female): X1X2Y (male) sex determination. In male meiosis I, the X1, X2, and Y chromosom...
During cell division, kinetochore microtubules (KMTs) provide a physical linkage between the chromosomes and the rest of the spindle. KMTs in mammalian cells are organized into bundles, so-called kinetochore-fibers (k-fibers), but the ultrastructure of these fibers is currently not well characterized. Here we show by large-scale electron tomography...
During eukaryotic cell division, chromosomes are linked to microtubules (MTs) in the spindle by a macromolecular complex called the kinetochore. The bound kinetochore microtubules (KMTs) are crucial to ensuring accurate chromosome segregation. Recent reconstructions by electron tomography (Kiewisz et al. 2021) captured the positions and configurati...
Centrosomes are membraneless organelles that nucleate microtubules. At their core is a pair of centrioles that recruit pericentriolar material (PCM), a phase-separated condensate. In many cell types, including human cells, centrosomes are surrounded by endoplasmic reticulum-derived membranes of unknown structure and function. Using volume electron...
Faithful chromosome segregation requires the assembly of a bipolar spindle, consisting of two antiparallel microtubule (MT) arrays having most of their minus ends focused at the spindle poles and their plus ends overlapping in the spindle midzone. In mammalian cells, bipolar spindles have bundles of kinetochore microtubules (KMTs), called kinetocho...
Centrosomes are cellular structures that nucleate microtubules. At their core is a pair of centrioles that recruit pericentriolar material (PCM). Although centrosomes are considered membraneless organelles, in many cell types, including human cells, centrosomes are surrounded by endoplasmic reticulum (ER)-derived membranes of unknown structure and...
During cell division, kinetochore microtubules (KMTs) provide a physical linkage between the spindle poles and the chromosomes. KMTs in mammalian cells are organized into bundles, so-called kinetochore-fibers (k-fibers), but the ultrastructure of these fibers is currently not well characterized. Here we show by large-scale electron tomography that...
During eukaryotic cell division, chromosomes are linked to microtubules (MTs) in the spindle by a macromolecular complex called the kinetochore. The bound kinetochore microtubules (KMTs) are crucial to ensuring accurate chromosome segregation. Recent electron tomography reconstructions (Kiewisz et al. 2021) captured the positions and configurations...
Crosslinking of FcεRI-bound IgE triggers the release of a large number of biologically active, potentially anaphylactic compounds by mast cells. FcεRI activation ought to be well-controlled to restrict adverse activation. As mast cells are embedded in tissues, adhesion molecules may contribute to limiting premature activation. Here we report that E...
en We present a software-assisted workflow for the alignment and matching of filamentous structures across a three-dimensional (3D) stack of serial images. This is achieved by combining automatic methods, visual validation, and interactive correction. After the computation of an initial automatic matching, the user can continuously improve the resu...
The endosomal sorting complex required for transport (ESCRT) mediates cellular processes that are related to membrane remodeling, such as multivesicular body (MVB) formation, viral budding and cytokinesis. Abscission is the final stage of cytokinesis that results in the physical separation of the newly formed two daughter cells. Although abscission...
Live-imaging of meiotic cell division has been performed in extracted spermatocytes of a number of species using phase-contrast microscopy. For the nematode Caenorhabditis elegans, removal of spermatocytes from gonads has damaging effects, as most of the extracted spermatocytes show a high variability in the timing of meiotic divisions or simply ar...
We introduce a new workflow that allows screening and selection of staged mammalian cells in mitosis prior to subsequent electron microscopy. We mainly describe four improved steps of specimen preparation. Firstly, we describe a method to efficiently enrich mammalian cells and attach them to sapphire discs; secondly, we report on the use of 3D-prin...
The spindle shows remarkable diversity, and changes in an integrated fashion, as cells vary over evolution. Here, we provide a mechanistic explanation for variations in the first mitotic spindle in nematodes. We used a combination of quantitative genetics and biophysics to rule out broad classes of models of the regulation of spindle length and dyn...
The spindle shows remarkable diversity, and changes in an integrated fashion, as cells vary over evolution. Here, we provide a mechanistic explanation for variations in the first mitotic spindle in nematodes. We used a combination of quantitative genetics and biophysics to rule out broad classes of models of the regulation of spindle length and dyn...
The spindle shows remarkable diversity, and changes in an integrated fashion, as cells vary over evolution. Here, we provide a mechanistic explanation for variations in the first mitotic spindle in nematodes. We used a combination of quantitative genetics and biophysics to rule out broad classes of models of the regulation of spindle length and dyn...
The lipids phosphatidylserine (PtdSer) and phosphatidylethanolamine (PtdEth) are normally asymmetrically localized to the cytosolic face of membrane bilayers, but can both be externalized during diverse biological processes, including cell division, cell fusion, and cell death. Externalized lipids in the plasma membrane are recognized by lipid-bind...
We present a software-assisted workflow for the alignment and matching of filamentous structures across a 3D stack of serial images. This is achieved by combining automatic methods, visual validation, and interactive correction. After an initial alignment, the user can continuously improve the result by interactively correcting landmarks or matches...
The nuclear permeability barrier depends on closure of nuclear envelope (NE) holes. Here, we investigate closure of the NE opening surrounding the meiotic spindle in C. elegans oocytes. ESCRT-III components accumulate at the opening but are not required for nuclear closure on their own. 3D analysis revealed cytoplasmic membranes directly adjacent t...
Chromosome segregation during male meiosis is tailored to rapidly generate multitudes of sperm. Little is known about mechanisms that efficiently partition chromosomes to produce sperm. Using live imaging and tomographic reconstructions of spermatocyte meiotic spindles in Caenorhabditis elegans, we find the lagging X chromosome, a distinctive featu...
Chromosome segregation during male meiosis is tailored to rapidly generate multitudes of sperm. Little is known about mechanisms that efficiently partition chromosomes to produce sperm. Using live imaging and tomographic reconstructions of spermatocyte meiotic spindles in Caenorhabditis elegans, we find the lagging X chromosome, a distinctive featu...
Chromosome segregation during male meiosis is tailored to rapidly generate multitudes of sperm. Little is known about mechanisms that efficiently partition chromosomes to produce sperm. Using live imaging and tomographic reconstructions of spermatocyte meiotic spindles in Caenorhabditis elegans, we find the lagging X chromosome, a distinctive featu...
During mitosis, the centrosome expands its capacity to nucleate microtubules. Understanding the mechanisms of centrosomal microtubule nucleation is, however, constrained by a lack of knowledge of the amount of soluble and polymeric tubulin at mitotic centrosomes. Here we combined light microscopy and serial-section electron tomography to measure th...
Chromosome segregation during male meiosis is tailored to rapidly generate multitudes of sperm. Little, however, is known about the mechanisms that efficiently segregate chromosomes to produce sperm. Using live imaging in Caenorhabditis elegans , we find that spermatocytes exhibit simultaneous pole-to-chromosome shortening (anaphase A) and pole-to-...
Spindle microtubules, whose dynamics vary over time and at different locations, cooperatively drive chromosome segregation. Measurements of microtubule dynamics and spindle ultrastructure can provide insight into the behaviors of microtubules, helping elucidate the mechanism of chromosome segregation. Much work has focused on the dynamics and organ...
The organization of microtubules in spindles is complex and not fully understood. Here we report on current advances in generating 3D reconstructions of staged spindles by serial-section electron tomography, exemplified by the first mitotic spindle in early Caenorhabditis elegans embryo. We then review how advances in correlative light microscopy a...
Centrioles are nine‐fold symmetric barrel‐shaped organelles that exist as mother‐daughter pairs that participate in the assembly of bipolar spindles and the formation of cilia and flagella. During S phase of each cell cycle, centrioles are precisely duplicated through a process that involves the formation of a new daughter next to each preexisting...
During mitosis, the centrosome expands its capacity to nucleate microtubules. Understanding the mechanisms of centrosomal microtubule nucleation is, however, constrained by a lack of knowledge of the amount of soluble and polymer tubulin at mitotic centrosomes. Here we combined light microscopy and serial-section electron tomography to measure the...
Spindle microtubules, whose dynamics vary over time and at different locations, cooperatively drive chromosome segregation. Measurements of microtubule dynamics and spindle ultrastructure can provide insight into the behaviors of microtubules, helping elucidate the mechanism of chromosome segregation. Much work has focused on the dynamics and organ...
We describe a routine method to locate cells of appropriate meiotic stages in the gonad of Caenorhabditis elegans males prior to 3D reconstruction of meiotic spindles by electron tomography. For this, serial semi-thick (300 nm) sections of whole worms are pre-screened and recorded at low magnification by transmission electron microscopy. Cells of i...
Cancer cell proliferation and insufficient blood supply can lead to the development of hypoxic areas in the tumor tissue. The adaptation to the hypoxic environment is mediated by a transcriptional complex called hypoxia-inducible factor (HIF). HIF protein levels are tightly controlled by oxygen-dependent prolyl hydroxylase domain proteins (PHDs). H...
Chemically active droplets are nonequilibrium systems that combine phase separation with chemical reactions. We here investigate how the activity introduced by the chemical reactions influences solid particles inside such droplets. We find that passive particles are centered in active droplets governed by first-order reactions. In autocatalytic act...
In oocytes of many organisms, meiotic spindles form in the absence of centrosomes [1-5]. Such female meiotic spindles have a pointed appearance in metaphase with microtubules focused at acentrosomal spindle poles. At anaphase, the microtubules of acentrosomal spindles then transition to an inter-chromosomal array, while the spindle poles disappear....
The dynamic instability of microtubules is a conserved and fundamental mechanism in eukaryotes. Yet microtubules from different species diverge in their growth rates, lattice structures, and responses to GTP hydrolysis. Therefore, we do not know what limits microtubule growth, what determines microtubule structure, or whether the mechanisms of dyna...
Theodor Boveri is considered as the “father” of centrosome biology. Boveri’s fundamental findings have laid the groundwork for decades of research on centrosomes. Here, we briefly review his early work on centrosomes and his first description of the centriole. Mainly focusing on centriole structure, duplication, and centriole assembly factors in C....
The mitotic spindle is a complex three-dimensional (3D) apparatus that functions to ensure the faithful segregation of chromosomes during cell division. Our current understanding of spindle architecture is mainly based on a plethora of information derived from light microscopy with rather few insights about spindle ultrastructure obtained from elec...
The mitotic spindle ensures the faithful segregation of chromosomes. Here we combine the first large-scale serial electron tomography of whole mitotic spindles in early C. elegans embryos with live-cell imaging to reconstruct all microtubules in 3D and identify their plus- and minus-ends. We classify them as kinetochore (KMTs), spindle (SMTs) or as...
Mitotic and meiotic spindles are microtubule-based structures to faithfully segregate chromosomes. Electron tomography is currently the method of choice to analyze the three-dimensional (3D) architecture of both types of spindles. Over the years, we have developed methods and software for automatic segmentation and stitching of microtubules in seri...
The co-existence of males, females and hermaphrodites, a rare mating system known as trioecy, has been considered as an evolutionarily transient state. In nematodes, androdioecy (males/hermaphrodites) as found in Caenorhabditis elegans, is thought to have evolved from dioecy (males/females) through a trioecious intermediate. Thus, trioecious specie...
Asymmetric partitioning is an essential component of many developmental processes. As spermatogenesis concludes, sperm are streamlined by discarding unnecessary cellular into cellular wastebags called residual bodies (RBs). During nematode spermatogenesis, this asymmetric partitioning event occurs shortly after anaphase II, and both microtubules an...