Abstract: The present invention relates to a method for monitoring the effect of an environmental factor on the proteome of a cell. Furthermore, cell populations are provided that comprise multiple cells each comprising an inserted tag sequence in an intron of said cell, wherein the tag is inserted in-frame with the preceding exonic sequence and wherein the intron into which the tag is inserted is different between cells.

Abstract: The present invention relates to compounds of formula compounds of formulae (I) by which transmembrane proteins such as SLC transporters can be unlocked to chemically-induced degradation, whereby a multitude of diseases can be addressed for the first time. Particularly, the present invention relates to compounds with the ability to induce degradation of SLC transporters via the ubiquitin-proteasome pathway. The invention also relates to the compounds and composition for use as medicaments as well as pharmaceutical compositions comprising these compounds, particularly for use as degraders of SLC transporters which are, e.g., associated with cancer and for use in the treatment of various diseases such as cancer. Furthermore, the present invention relates to a method for treating a disease or condition, such as cancer, comprising administering the compound of the present invention.

Abstract: The present invention relates to compounds with the ability to stimulate/induce ubiquitination of a target protein/target proteins. The compounds of the present invention may stimulate/induce ubiquitination of a target protein/target proteins; i.e. via degradation of a target protein/target proteins by the cullin-RING ubiquitin ligase (CRL). Such target protein/target proteins may be proteins involved in diseases, like cancer, metabolic disorder, infectious disease and/or neurological disorder. The invention further relates to a method for identifying/obtaining and/or testing a compound able to induce ubiquitination of a target protein/target proteins. The invention also relates to the compounds and composition for use as medicaments as well as pharmaceutical compositions comprising these compounds. Particularly, the compounds of the present invention may degrade proteins associated with cancer, metabolic disorder, infectious disease and/or neurological disorder.

Abstract: The invention relates to peripheral blood mononuclear cell (PBMC) monolayers or bone-marrow cell monolayers and methods for its culture and corresponding uses of said monolayers. The present invention also relates, in some aspects, to screening methods comprising the PBMC monolayer or bone-marrow cell monolayer of the invention for determination of response or lack of response of a disease to a therapeutic agent and/or drug screening methods. In some aspects, the invention further relates to methods for diagnosing a disease or predisposition to a disease in a PBMC donor or bone-marrow cell donor comprising the PBMCs/bone-marrow cells cultured according to the method of the invention and/or to methods for determining whether the disease is likely to respond or is responsive to treatment with a therapeutic agent.

Abstract: The present invention relates to a method for diagnosing myeloid malignancy comprising determining the presence of a mutant allele of the calreticulin gene. Also genomic sequences, cDNA sequences, mRNA sequences and protein sequences of the mutant calreticulin are subject of the present invention. Further, the invention relates to medical uses of inhibitors of mutant calreticulin.

Abstract: The present invention relates to a method for identifying compounds or agents able to induce ubiquitination of a protein of interest. Further, the present invention relates to compounds/agents obtainable by the method of the present invention. Furthermore, the present invention relates to a method for treating cancer or other diseases comprising administering the chemical compound or agent obtainable by the method of the present invention. Moreover, the present invention relates to a eukaryotic cell comprising enhanced cullin-RING ubiquitin ligase (CRL) activity and/or constantly neddylated cullin-RING ubiquitin ligases/CRLs.

Abstract: The invention relates to methods for determining the selectivity of a test compound and related methods such as methods for determining whether a subject suffering from cancer will respond or is responsive to treatment with a test compound or compositions comprising more than one test compound.

Abstract: The present invention relates to methods for determining the propensity of cells to interact in a population of cells comprising at least two distinguishable subpopulations of cells. In addition, the present invention provides methods for diagnosing a disease or predisposition to a disease of a cell donor, wherein the method comprises the determination of the propensity of cells to interact in a population of cells obtained from the donor, wherein the population of cells comprises at least two distinguishable subpopulations of cells. The invention also provides methods for determining whether a subject suffering from or predisposed to a disease will respond or is responsive to treatment with a therapeutic agent by determining the alteration of the propensity of cells to interact in a population of ceils obtained from the subject, wherein the population of cells comprises at least two distinguishable subpopulations of cells.

Abstract: The present invention relates to a method for diagnosing myeloid malignancy comprising determining the presence of a mutant allele of the calreticulin gene. Also genomic sequences, cDNA sequences, mRNA sequences and protein sequences of the mutant calreticulin are subject of the present invention. Further, the invention relates to medical uses of inhibitors of mutant calreticulin.

Abstract: The present invention relates to a method for diagnosing myeloid malignancy comprising determining the presence of a mutant allele of the calreticulin gene. Also genomic sequences, cDNA sequences, mRNA sequences and protein sequences of the mutant calreticulin are subject of the present invention. Further, the invention relates to medical uses of inhibitors of mutant calreticulin.

Abstract: The present invention provides a novel method for preparing a sequencing library and studying molecular interactions involving a nucleic acid. In particular, the invention relates to a method for preparing a sequencing library, the method comprising the addition of an agent binding to chromatin to a sample comprising a nucleic acid; isolating chromatin bound by said agent; addition of transposase to the isolated chromatin; isolating nucleic acid from chromatin; and obtaining a sequencing library. Moreover, the present invention relates to a method for mapping of molecular interactions involving a nucleic acid, the method comprising the addition of an agent binding to chromatin to a sample comprising a nucleic acid; isolating chromatin bound by said agent; addition of transposase to the isolated chromatin; isolating nucleic acid from chromatin; amplification of nucleic acid; sequencing of amplified nucleic acid; and identifying molecular interactions.

Abstract: The present invention relates to an antibody that specifically binds to a mutant calreticulin protein, wherein the variable region of the heavy chain of said antibody comprises a CDR-H3 region having an amino acid sequence as depicted in SEQ ID NO.: 3, or a CDR sequence having 75% or more amino acid identity to said CDR; or wherein the variable region of the heavy chain of said antibody comprises a CDR-H3 region having an amino acid sequence as depicted in SEQ ID NO.: 6, or a CDR sequence having 75% or more amino acid identity to said CDR. Hybridoma 8B2-H6-10.7 deposited under accession number DSM ACC3249 with the depositary institute DSMZ on Sep. 12, 2014 as well as antibodies obtainable therefrom are subject of the present invention. The antibodies provided herein can be used in the diagnosis of or therapeutic intervention in myeloid malignancies.

Abstract: The present invention relates to an (S)-enantiomer of an aminoheteroaryl compound for use in treating and/or preventing cancer in a subject. The invention further relates to a pharmaceutical composition comprising said compound. Another aspect of the invention is directed to an in vitro method for determining the effectiveness of said (S)-enantiomer of an aminoheteroaryl compound, or said pharmaceutical composition, the method comprising the steps of: (a) obtaining a cell or tissue sample from a subject; and (b) determining the subject's NUDT1/MTH1-status; wherein a NUDT1/MTH1-positive cell or tissue sample is indicative of an effective treatment and/or prevention of cancer. In addition, provided herein is a screening method for identifying a target of an (S)-enantiomer of an aminoheteroaryl compound. Furthermore, in context of this invention, the herein described compounds inhibit the biological activity of MTH1.

Abstract: The present invention relates to an (S)-enantiomer of an aminoheteroaryl compound for use in treating and/or preventing cancer in a subject. The invention further relates to a pharmaceutical composition comprising said compound. Another aspect of the invention is directed to an in vitro method for determining the effectiveness of said (S)-enantiomer of an aminoheteroaryl compound, or said pharmaceutical composition, the method comprising the steps of: (a) obtaining a cell or tissue sample from a subject; and (b) determining the subject's NUDT1/MTH1-status; wherein a NUDT1/MTH1-positive cell or tissue sample is indicative of an effective treatment and/or prevention of cancer. In addition, provided herein is a screening method for identifying a target of an (S)-enantiomer of an aminoheteroaryl compound. Furthermore, in context of this invention, the herein described compounds inhibit the biological activity of MTH1.

Abstract: Mutations in calreticulin are discovered to be linked to myeloid malignancies. Disclosed are genomic sequences, cDNA sequences, mRNA sequences and protein sequences of mutant calreticulin that are linked to myeloid malignancies. Also disclosed are methods for diagnosing myeloid malignancy comprising determining the presence of a mutant allele of the calreticulin gene. Also disclosed are related compositions, kits and methods, including the medical use of inhibitors of mutant calreticulin.