Friedrich Miescher Institute for Biomedical Research
Friedrich Miescher Institute for Biomedical Research | Date: 2017-08-02
The present invention relates to a method for treating breast cancer in a subject having a breast cancer of the estrogen receptor (ER) negative type, which method comprises the step of administering to said subject a therapeutically effective amount of a modulator of the Large Tumor Suppressor Kinase (LATS). Also provided are a si RNA decreasing or silencing the expression of the Large Tumor Suppressor Kinase (LATS), and an antibody specifically binding to the Large Tumor Suppressor Kinase (LATS), for use to treat breast cancer of the estrogen receptor (ER) negative type.
Friedrich Miescher Institute for Biomedical Research | Date: 2017-04-19
The present application provides a method for treating an influenza virus infection in a subject characterised in that a therapeutically effective amount of a modulator of the ubiquitin-binding property of HDAC6 is administered to said subject. The present application also provides an antibody binding to HADC6 and decreasing or blocking its ubiquitin-binding properties for use in treating an influenza virus infection.
Friedrich Miescher Institute for Biomedical Research and University of Basel | Date: 2017-01-04
The application relates to a method for predicting a risk for preeclampsia in a subject, said method comprising analysing a sample from the subject for the level of expression of miR455 and comparing the level of expression of miR455 in the sample from the subject to the levels of miR455 in a control sample, wherein a significantly lower expression of miR455 as compared to the expression of miR455 in the control is indicative of a risk for preeclampsia.
Friedrich Miescher Institute for Biomedical Research | Date: 2017-04-26
The present application relates to a method for the targeted formation of heterochromatin and/or induction of epigenetic gene silencing in a cell using a small RNA, said method comprising the step of inhibiting the Paf1 complex in said cell and the step of contacting said cell with a small RNA targeted to a region of the genome of the cell, said region being the region where heterochromatin formation and/or induction of epigenetic gene silencing should be induced.
Friedrich Miescher Institute for Biomedical Research | Date: 2017-06-07
The present invention provides an isolated nucleic acid molecule comprising, or consisting of, the nucleic acid sequence of SEQ ID NO:1 or a nucleic acid sequence of at least 200 bp having at least 80% identity to said sequence of SEQ ID NO:1, wherein said isolated nucleic acid molecule specifically leads to the expression in rod photoreceptors of a gene when operatively linked to a nucleic acid sequence coding for said gene.
Friedrich Miescher Institute for Biomedical Research | Date: 2017-05-10
The invention relates to a pharmaceutical combination which comprises (a) a compound inhibiting BRAFV600E and (b) a compound which inhibits MerTK activation; for simultaneous, separate or sequential use; a commercial package or product comprising such a combination as a combined preparation for simultaneous, separate or sequential use; and to a method of treatment of a warm-blooded animal, especially a human.
Zhu P.,Friedrich Miescher Institute for Biomedical Research
Nature protocols | Year: 2012
Optogenetic approaches allow the manipulation of neuronal activity patterns in space and time by light, particularly in small animals such as zebrafish. However, most techniques cannot control neuronal activity independently at different locations. Here we describe equipment and provide a protocol for single-photon patterned optical stimulation of neurons using a digital micromirror device (DMD). This method can create arbitrary spatiotemporal light patterns with spatial and temporal resolutions in the micrometer and submillisecond range, respectively. Different options to integrate a DMD into a multiphoton microscope are presented and compared. We also describe an ex vivo preparation of the adult zebrafish head that greatly facilitates optogenetic and other experiments. After assembly, the initial alignment takes about one day and the zebrafish preparation takes <30 min. The method has previously been used to activate channelrhodopsin-2 and manipulate oscillatory synchrony among spatially distributed neurons in the zebrafish olfactory bulb. It can be adapted easily to a wide range of other species, optogenetic probes and scientific applications.
Schubeler D.,Friedrich Miescher Institute for Biomedical Research |
Schubeler D.,University of Basel
Nature | Year: 2015
Cytosine methylation is a DNA modification generally associated with transcriptional silencing. Factors that regulate methylation have been linked to human disease, yet how they contribute to malignances remains largely unknown. Genomic maps of DNA methylation have revealed unexpected dynamics at gene regulatory regions, including active demethylation by TET proteins at binding sites for transcription factors. These observations indicate that the underlying DNA sequence largely accounts for local patterns of methylation. As a result, this mark is highly informative when studying gene regulation in normal and diseased cells, and it can potentially function as a biomarker. Although these findings challenge the view that methylation is generally instructive for gene silencing, several open questions remain, including how methylation is targeted and recognized and in what context it affects genome readout. © 2015 Macmillan Publishers Limited.
Schubeler D.,Friedrich Miescher Institute for Biomedical Research
Science | Year: 2012
Mammalian methylomes reveal how DNA methylation is infl uenced by the underlying nucleotide sequence.
Agency: European Commission | Branch: H2020 | Program: ERC-COG | Phase: ERC-CoG-2015 | Award Amount: 2.00M | Year: 2017
RNAi refers to the ability of small RNAs to silence expression of homologous sequences. A surprising link between epigenetics and RNAi was discovered more than a decade ago, and I was fortunate enough to be involved in this exciting field of research from the beginning. It is now well established that endogenous small RNAs have a direct impact on the genome in various organisms. Yet, the initiation of chromatin modifications in trans by exogenously introduced small RNAs has been inherently difficult to achieve in all eukaryotic cells. This has sparked controversy about the importance and conservation of RNAi-mediated epigenome regulation and hampered systematic mechanistic dissection of this phenomenon. Using fission yeast, we have discovered a counter-acting mechanism that impedes small RNA-directed formation of heterochromatin and constitutes the foundation of this proposal. Our goal is to close several knowledge gaps and test the intriguing possibility that the suppressive mechanism we discovered is conserved in mammalian cells. We will employ yeast and embryonic stem cells and use cutting-edge technologies (i.e., chemical mutagenesis combined with whole-genome sequencing, genome editing with engineered nucleases, and single-cell RNA sequencing) to address fundamental, as yet unanswered questions. My proposal consists of four major aims. In aim 1, I propose to use proteomics approaches and to perform yeast genetic screens to define additional pathway components and regulatory factors. Aim 2 builds on our ability to finally trigger de novo formation of heterochromatin by synthetic siRNAs acting in trans, addressing many of the outstanding mechanistic questions that could not be addressed in the past. In Aims 3 and 4, experiments conducted in yeast and mouse cells will elucidate missing fragments critical to our understanding of the conserved principles behind RNAi-mediated epigenetic gene regulation.