News

Imaging protein three-dimensional nanocrystals with cryo-EM.

M van Heel M & JP Abrahams report in Acta Crystallogr.

Flash-cooled three-dimensional crystals of the small protein lysozyme with a thickness of the order of 100 nm were imaged by 300 kV cryo-EM on a Falcon direct electron detector. The images were taken close to focus and to the eye appeared devoid of contrast. Fourier transforms of the images revealed the reciprocal lattice up to 3 Å resolution in favourable cases and up to 4 Å resolution for about half the crystals.

E Snaar-Jagalska reports in Biochem Biophys Res Commun.

TGF-β plays a dual role in cancer; in early stages it inhibits tumor growth, whereas later it promotes invasion and metastasis. TGF-β is thought to be pro-invasive by inducing epithelial-to-mesenchymal transition (EMT) via induction of transcriptional repressors, including Slug and Snail. In this study, we investigated the role of Snail and Slug in TGF-β-induced invasion in an in vitro invasion assay and in an embryonic zebrafish xenograft model.

A Meijer, F Verbeek & H Spaink report in Gene Expr Patterns.

The function and structure of LysM-domain containing proteins are very diverse. Although some LysM domains are able to bind peptidoglycan or chitin type carbohydrates in bacteria, in fungi and in plants, the function(s) of vertebrate LysM domains and proteins remains largely unknown. In this study we have identified and annotated the six zebrafish genes of this family, which encode at least eight conceptual LysM-domain containing proteins.

JP Abrahams reports in ACS Chem Neurosci.

The cellular polyamines spermine, spermidine, and their metabolic precursor putrescine, have long been associated with cell-growth, tumor-related gene regulations, and Alzheimer's disease. Here, we show by in vitro spectroscopy and AFM imaging, that these molecules promote aggregation of amyloid-beta (Aβ) peptides into fibrils and modulate the aggregation pathways.

H Spaink & A Meijer report in Dis Model Mech.

Toll-like receptors (TLRs) are an important class of pattern recognition receptors (PRRs) that recognize microbial and danger signals. Their downstream signaling upon ligand binding is vital for initiation of the innate immune response.

Targeted radiosensitization in prostate cancer.

E Danen reports in Curr Pharm Des.

Radiotherapy is one of the treatment options for locally or regionally advanced prostate cancer, but radioresistance of prostate cancer cells is a practical limitation of radiotherapy. The identification of molecular targets of radioresistance in prostate cancer is important to improve therapeutic intervention.

E Danen reports in Int J Biochem Cell Biol.

Interactions with the extracellular matrix (ECM) provide cells with physical and chemical cues that act in concert with growth factors to support survival and proliferation. Transmembrane receptors of the integrin family mediate ECM attachment and play important roles in sensing and responding to ECM properties.

Prof Dr Doris Heinrich started her group on Feb 1. Dr Heinrich's research interests are on the physics of living cells, especially their cytoskeleton dynamics under defined external stimuli. Meet her at the CellObservatory.

Parallel Nanometric 3D Tracking of Intracellular Gold Nanorods Using Multifocal Two-Photon Microscopy.

T Oosterkamp & J van Noort report in Nano Letters.

We report a novel technique for long-term parallel three dimensional (3D)-tracking of gold nanorods in live cells with nanometer resolution.

J. Brouwer, M. Noteborn & Claude Backendorf report in Nature CCD.

Mitotic catastrophe is an oncosuppressive mechanism that senses mitotic failure leading to cell death or senescence. As such it protects against aneuploidy and genetic instability and its induction in cancer cells by exogenous agents is currently seen as a promising therapeutic endpoint.

R Dame reports in PLOS Gen.

The Escherichia coli curved DNA binding protein A (CbpA) is a poorly characterised nucleoid associated factor and co-chaperone. It is expressed at high levels as cells enter stationary phase. Using genetics, biochemistry, and genomics, we have examined regulation of, and DNA binding by, CbpA.

H Spaink, M Schaaf & A Meijer report in J Immunol.

Deficiency in Src homology region 2 domain-containing phosphatase 1/protein tyrosine phosphatase nonreceptor type 6 (SHP1/PTPN6) is linked with chronic inflammatory diseases and hematological malignancies in humans. In this study, we exploited the embryonic and larval stages of zebrafish (Danio rerio) as an animal model to study ptpn6 function in the sole context of innate immunity.

B vd Water reports in J Appl Tox.

Most of the current in vitro carcinogenicity assays assess the potential carcinogenic properties of chemicals through the detection of inflicted DNA damage or subsequent chromosome damage and gene mutations. Unfortunately, these assays generally do not provide mechanistic insight into the reactive properties of a chemical.

Rosalie Driessen and Shuning He win the Cell Observatory Publication of 2012 Award.

B van de Water, F Verbeek & J Meerman report in PLOSOne.

Nuclear entry and exit of the NF-κB family of dimeric transcription factors plays an essential role in regulating cellular responses to inflammatory stress. The dynamics of this nuclear translocation can vary significantly within a cell population and may dramatically change e.g. upon drug exposure. Furthermore, there is significant heterogeneity in individual cell response upon stress signaling. In order to systematically determine factors that define NF-κB translocation dynamics, high-throughput screens that enable the analysis of dynamic NF-κB responses in individual cells in real time are essential.

Submit your article for selection as publication of the year / Cell Observatory drinks

Dear colleagues,

To celebrate the start of the new year there will be drinks and snacks for all members (and users) of the Cell Observatory (organized by the newly established Cell Observatory drinks committee) on January 24 at 16.00h in the Cell Observatory lounge.

R Dame reports in Nat. Comm.

Architectural proteins have an important role in shaping the genome and act as global regulators of gene expression. How these proteins jointly modulate genome plasticity is largely unknown. In archaea, one of the most abundant proteins, Alba, is considered to have a key role in organizing the genome.

N Pannu reports in Nucl. Acid Res.

Repairing damaged DNA is essential for an organism's survival. UV damage endonuclease (UVDE) is a DNA-repair enzyme that can recognize and incise different types of damaged DNA. We present the structure of Sulfolobus acidocaldarius UVDE on its own and in a pre-catalytic complex

M Schaaf and C Backendorf report in Adv. Health. Mat.

Folic acid-modified mesoporous silica nanoparticles are designed for cellular and nuclear targeted drug delivery. Camptothecin is efficiently delivered to human cancer cells resulting in apoptosis without premature leakage.

R Dame and J van Noort report in Nucl. Acid Res.

Archaeal chromatin proteins share molecular and functional similarities with both bacterial and eukaryotic chromatin proteins. These proteins play an important role in functionally organizing the genomic DNA into a compact nucleoid.

John Meerman, Bob van de Water, Marjo de Graauw report in Biochemical Pharmacology.

Cisplatin-induced nephrotoxicity is an important limiting factor for cisplatin use. Tumor necrosis factor α (TNF-α) is known to contribute to cisplatin-induced nephrotoxicity by inducing an inflammatory process aggravating the primary injury, thereby resulting in acute kidney injury (AKI).

Meeting report by Remus Dame in Molecular Microbiology.

Bacterial genomes are organized by a plethora of chromatin proteins and physical mechanisms. This organization appears to be hierarchical with DNA folding events at the nm scale influencing higher levels of chromosome organization. Besides acting in shaping the genome these factors also play important regulatory roles in numerous DNA transactions.

Herman Spaink reports in Gene.

The Japanese eel is a much appreciated research object and very important for Asian aquaculture; however, its genomic resources are still limited. We have used a streamlined bioinformatics pipeline for the de novo assembly of the genome sequence of the Japanese eel from raw Illumina sequence reads.

John van Noort reports in PNAS.
Nucleosome positioning dictates eukaryotic DNA compaction and access. To predict nucleosome positions in a statistical mechanics model, we exploited the knowledge that nucleosomes favor DNA sequences with specific periodically occurring dinucleotides.

Erno Vreugdenhil reports in Molecular Psychiatry.
Glucocorticoids (GCs) secreted after stress reduce adult hippocampal neurogenesis, a process that has been implicated in cognitive aspects of psychopathology, amongst others. Yet, the exact role of the GC receptor (GR), a key mediator of GC action, in regulating adult neurogenesis is largely unknown.

Paper by Annemarie Meijer & Herman Spaink.

The zebrafish has proven itself as an excellent model to study vertebrate innate immunity. It presents us with possibilities for in vivo imaging of host-pathogen interactions which are unparalleled in mammalian model systems.

The first five seconds in the life of a clathrin-coated pit.

Tom Kirchausen et al report in Cell

Coated pits assemble by growth of a clathrin lattice, which is linked by adaptors to the underlying membrane. How does this process start?

Paper by the Erno Vreugdenhil.

Doublecortin-like (DCL) exhibits high amino acid sequence identity (73%) over its entire length with the neurogenesis marker doublecortin (DCX), and during embryogenesis, DCL is specifically expressed in radial glia cells, the progenitors for neurons.

January 2012 – Mathieu Noteborn provides a view into the life of a scientist and education program director through his weblog.

Week 50 – Susan Cox and colleagues reveal a faster timescale of podosome dynamics using Bayesian localization microscopy.

Week 49 - Scientists in Ohio developed a mathematical model that predicts how the protein myoferlin may effect cancer cell invasion.

Week 48 - Are electron tweezers possible?

November 2011 - The Foundation for Fundamental Research on Matter (FOM) funds a new research programme led by John van Noort.

Week 45 - Khalid Salaita and colleagues developed a fluorescent sensor that shows the mechanical tension experienced by receptors in the membrane of living cells.

November 2011 - By creating a live connection with the microscope 70 m from its location, deputy Liesbeth Spies officially opened the Netherlands Centre for Electron Nanoscopy (NeCEN) on October 27th.

November 2011 - Dr. Annemarie H. Meijer at the Cell Observatory will be coordinator of a new Marie Curie Initial Training Network.

October 2011 - NeCEN, a new high quality centre for electron microscopy, opens its doors in Leiden on October 27th.

Week 42 – A group of UK scientists reveals detailed information about remodeling of actin at the synapses of natural killer cells.

September 2011 - Prof. Herman P. Spaink of the Institute of Biology (IBL) received funding from the Leiden University Fund (LUF) to screen for new drugs
for treatment of tuberculosis.

Week 39 - Daniela Nicastro and colleagues resolved controversies about doublet microtubules in flagella using cryo-electron tomography.

Week 38 – David Baddely and coworkers developed a practical method for 4D super-resolution microscopy in thick samples.

Publication of the week #37

Week 37 - A research group in California developed a fluorescence microscope of 1.9 gram.

September 2011 -Mathieu Noteborn gives insight into the life of a scientist and education program director through his weblog.

Week 34 - Scientists at Yale University performed two-color STED microscopy in living cells for the first time.

Publication of the week #33

Week 33 – A research group in the US developed a new fluorescent marker that switches from orange to far-red after irradiation with blue-green light.

Week 32 – Scott Fraser and colleagues combined two-photon scanning and light-sheet microscopy in order to combine the advantages of both techniques.

Week 31 – A research group led by Gabriel Popescu developed a new optical method for measuring growth of individual cells during the cell cycle.

July 2011 - New publications on software by Pavol Skubak and Navraj Pannu have been cited over a hundred times within the first three months.

Week 30 – A US-Australian research group shows that broadband X-ray sources can be used for imaging.

July 2011 - The Cell Observatory will house the Netherlands Centre for Electron Nanoscopy NeCEN. You can find regular updates on www.necen.nl.

Publication of the week

Week 28 - Josef Lazar and colleagues studied membrane proteins using two-photon polarization microscopy. They obtained results on structure, conformation and protein-protein interactions.

July 2011- On the afternoon of Monday July 4th, about forty students of this summer course visited the Cell Observatory

Week 27 – A US research group shows that mammalian cells exhibit specific left-right asymmetry when cultured in ring-shaped micropatterns. This asymmetry depends on their phenotype and the functionality of the actin cytoskeleton.

Week 26 - William Grover and coworkers developed a method to measure single-cell density by using a microfluidic chip.

week 25 - A research group led by Kevin Sullivan reveals dynamic assembly of a histone fold protein complex during the cell cycle.

Week 24 – A group of US researchers claims to be the first to have imaged human rod photoreceptors noninvasively.

Week 23 – Scientists from Stanford University showed that single walled carbon nanotubes can be useful fluorophores for imaging through deep tissue.

Week 22 - Scientists at the University of Twente have developed a lens that can reach a sub-100 nm resolution with visible light.

Week 21 - A group of US scientists can force tumors to secrete detectable biomarkers. This method may provide the basis for a new way of screening for cancer.

Receive updates on lectures, news and the journal club automatically by following the Cell Observatory on twitter.

John Reif chairs journal club on May 25th

May 2011 - Professor John Reif from Duke University will chair an interdisciplinary discussion on DNA nanostructures and devices.

Week 19 - A research group led by Garry Nolan measured 34 parameters simultaneously with single-cell mass cytometry.

week 18 - Christine Chaffer and colleagues demonstrate that differentiated cells can spontaneously convert to stem-like cells. The US research group reveals this plasticity for human mammary epithelial cells (HMECs).

April 2011 - The movie shows how the building that will house the Netherlands Centre for Electron Nanoscopy (NeCEN) was built.

Week 17 – Research of Marisa Müller and colleagues provides more insight into the specific localization of mRNA. They found that specific mRNA recognition takes place after transport out of the nucleus and is mediated by a cytoplasmic complex.

Week 16 - A Dutch research group experienced third-harmonic generation (THG) microscopy to be a useful tool for brain imaging without contrast agents or fluorescent dyes. This finding may bring noninvasive optical biopsy of brain tissue one step closer.

Week 15 - Scientists of the University of California and the Florida State University developed a new tool for correlated light and electron microscopy. They designed miniSOG, a small encodable protein that “may do for EM what Green Fluorescent Protein did for fluorescence microscopy”*.

Week 12 - Thomas Planchon and colleagues developed a microscope that reaches an isotropic 3D resolution down to 0,3 μm in living cells.

Week 11 - Is it a model or a tool? Hazel Sive proposes new definitions to distinguish biological systems that recapitulate human disorders from systems without this precise correspondence.

February 2011 - On February 24th, forty-seven members of the Netherlands Academy of Technology and Innovation (AcTI) visited Leiden.

Week 10 – A group of Chinese and US scientists claims to have found a new role for tumour suppressor p53.

March 2011 - The building for NeCEN will be delivered before Pentecost, long before the official opening in late October. The housing for the centre is built right next to the Cell Observatory.

Week 9 - Scientists from the University of Illinois developed a method for measuring displacements of fluorophores with single molecule sensitivity.

February 2011 - Ralph Carvalho, Jan de Sonneville and other colleagues from the Cell Observatory published this new method in PloS ONE on February 16th.

Week 8 - This paper will be discussed in the journal club on Thursday. The authors describe how they use spin-images to characterize protein surfaces and how similar regions can be discovered using this method.

February 24th 12:30-14:00
Location: Cell Observatory lecture room
Chair: Joris Slob, LIACS
Subject: Discovering similar regions on protein surfaces

Week 7 – A group of scientists from Belgium, Switzerland and The Netherlands has made a 3D reconstruction of a nanoparticle at atomic resolution.

Week 6 - Henry Chapman and colleagues have developed a method for protein structure determination with femtosecond X-ray laser pulses.

Week 5 - Scientists at EMBL have developed software that is able to identify cells of interest and collect detailed information automatically.

January 2011 - SV LIFE recommended Nora Goosen because she is able to provide the foundation for difficult subject matter with her creative, enthusiastic and clear way of teaching.

Week 4 - Scientists of the University of North Carolina have identified the first mammalian micro RNA that inhibits neuronal apoptosis.

January 2011 – Marin van Heel from Imperial College London chaired the first Cell Observatory Journal Club session on January 14th. He helped PhD and MSc students discuss two articles about “4D cryo-EM: biological complexes in action”.

Week 3 – A group of scientists from Tenessee has developed a faster method for identifying ligands that may bind to protein targets. They developed a new version of the program Autodock 4, ran it on a supercomputer and concluded that in 1 day “about 300,000 compounds can be docked in a flexible ligand fashion or about 11 million compounds docked rigidly.”*

January 2011 - During the New Year's reception on January 10th, the results of the "Discoverer of the Year 2010" contest were announced.

Week 2 - This paper will be discussed during the journal club on Friday. The article describes research of Niels Fischer and his colleagues on tRNA movement through the ribosome. They use cryo electron microscopy to obtain about 2,000,000 images. Computational sorting of these images resulted in 50 distinct three dimensional reconstructions that provide insight in the translocation step of protein synthesis.

Week 51 - The axial resolution of a confocal microscope can be improved, by simply shaping the incident beam and placing a mirror behind the sample. Scientists of the Fresnel Institute in France published this finding in Physical Review Letters on November 12th.

Publication of the week

Week 50 - A research team of the University of Michigan has designed a new bifunctional molecule: it can bind Zn2+ and Cu2+ and interact with A-beta peptides at the same time. Accumulation of these metal ions and A-beta aggregates may be involved in Alzheimer's disease and therefore this molecule may be useful for further Alzheimer's disease research and therapeutic use.

November 2010 - By cutting a huge DNA string, Jan Pieter Abrahams officially opened the Cell Observatory on November 29th.

June 2010, two very powerful electron microscopes of the Netherlands Centre for Electron Nanoscopy will be housed by the Cell Observatory. Jan Pieter tells more about this first national facility for electron microscopy and explains what makes it special (in Dutch).

Publication of the week

Cells may have simpler modes of gene expression than generally thought. According to the group of Robert Singer, transcription of constitutive genes in yeast is not coordinated, not even if genes are functionally related.

October 2010 - The Cell Observatory will house the Netherlands Centre for Electron Nanoscopy (NeCEN) from april 2011. Two new cryo-transmission electron microscopes will be placed in a temporary expansion of the building. The first microscope has arrived and funds for the second are secured.

May 20, 2010, U.S. Scientist Craig Venter announced his team had succeeded in producing bacterial DNA in their laboratory and introducing this DNA into a bacteria whose own DNA had been removed. The next day, reporters from RTL4 asked Mathieu to explain this new discovery.

May 2010:NWO (Nederlandse organisatie voor Wetenschappelijk Onderzoek) has agreed to finance the first microscope of NeCEN (Nederlands Centrum voor Elektronen Nanoscopie). This microscope will be placed in the Cell Observatory.

In what could be described as a coherent superposition of science and media art, this documentary contributes to the public debate about genetic modification for advanced biosolar cells with a non-normative approach. It exposes straight into mass media public space the aesthetics of modern life science as it develops in the minds of scientists and the ethical dilemma's that arise, while leaving it to the observer to take a moral position on the issues raised.

A group of six PhD and master students has been set up, in order to start up cross-institutional journal clubs. All institutes involved in the Cell Observatory are represented in this 'hot group'.

Professor Ten Cate has been appointed Scientific Director of the Institute of Biology Leiden for a period of four years with effect from September 1, 2010.