Highlights Methods

Breast epithelial cells in culture.
Breast epithelial cells in culture.

3D Screening for Breast Cancer Drugs

Radiation therapy is an important part of breast cancer treatment. Sometimes, however, tumor cells become increasingly resistant to radiation damage. Now a screening system has been developed which allows the investigation of artificial, three-dimensional microtissue to determine which chemotherapeutic drugs can resensitize the breast cancer cells to radiation. The three-dimensionality of the tissue simulates the natural conditions more closely than two-dimensional cell culture screening systems.

Nataša Anastasov et al.: A 3D-Microtissue-based Phenotypic Screening of Radiation Resistant Tumor Cells with Synchronized Chemotherapeutic Treatment. BMC Cancer 15:466 (2015) | doi:10.1186/s12885-015-1481-9

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Breast Cancer Research: Mini Breasts Grown in Petri Dishes

In Germany approximately 70,000 women are diagnosed with breast cancer every year. Despite significant progress in treatment, rare, particularly aggressive forms of breast cancer are still poorly understood. Now scientists have developed an assay to establish a complex, 3D in vitro system from individual human mammary gland cells that mimics the development of human mammary glands. By means of this method, organ development, the role of stem cells and the development of breast cancer can be analyzed in detail.

Jelena R. Linnemann et al.: Quantification of Regenerative Potential in Primary Human Mammary Epithelial Cells.  Development 142  (2015) | doi:10.1242/dev.123554

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CRISPR/Cas: Efficient Editing of the Genome

A new genetic method is currently causing quite a stir and electrifying life scientists: the CRISPR/Cas technology, with which genomic DNA can be edited precisely, quickly and at low cost. By deploying molecular biological tricks, scientists of Helmholtz Zentrum München, together with researchers in Berlin, have collaborated to make the technique significantly more efficient, increasing the success rate of the method by up to eightfold.

Van Trung Chu et al.: Increasing the Efficiency of Homology-directed Repair for CRISPR-Cas9-induced Precise Gene Editing in Mammalian Cells. Nature Biotechnology 33( 2015) | doi:10.1038/nbt.3198

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Improvement of Diagnostic Imaging

Magnetic resonance imaging (MRI) is a high-resolution method for clinical diagnostic imaging. Frequently, additional contrast agents are used to illustrate the specific tissue structures and pathological processes. In this case, however, the image signal does not correlate with the actual quantitative concentration of the contrast agent. Using imaging mass spectrometry (MALDI-MS imaging), researchers have now developed a method that allows the specific determination of the contrast agent concentration, thus improving the informative value of the imaging.

Michaela Aichler et al.:  Spatially Resolved Quantification of Gd (III)-based Magnetic Resonance Agents in Tissue by MALDI Imaging Mass Spectrometry after in vivo MRI. Angewandte Chemie - International Edition | doi: 10.1002/ange.201410555

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Identification of Cell Types Using Statistics

Cell populations have a high heterogeneity, even when they consist of the same type of cells. To determine various types of cells, scientists analyze the respective active transcriptome – in the form of RNA molecules – of the individual cells. However, confounding factors, such as short-term changes in gene expression due to the cell cycle or differentiation processes, can influence the result. Scientists have now developed a bioinformatics model that statistically determines such confounding factors and takes single cell types into account in the analysis.

Florian Buettner et al.: Computational Analysis of Cell-to-cell Heterogeneity in Single-cell RNA-Sequencing Data Reveals Hidden Subpopulation of Cells. Nature Biotechnology 33 (2015) |doi: 10.1038/nbt.3102

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Faster Collection of Extensive Metabolic Data

Metabolomics is a new approach in metabolic research, looking at the metabolic properties holistically - that is, involving conversion rates, interaction and spatial and temporal separation of individual metabolic pathways. Genetic and microbial influences are considered. Metabolomics data are extremely complex, so refined biological and mathematical analysis methods are needed. HMGU scientists use ultra high resolution mass spectrometry to obtain detailed information on the metabolic status of a sample in a very short time.

Michael Witting et al.: DI-ICR-FT-MS-based High-throughput Deep Metabotyping: a Case Study of the Caenorhabditis elegans–Pseudomonas aeruginosa Infection Model. Analytical and Bioanalytical Chemistry 407 (2015) | doi: 10.1007/s00216-014-8331-5

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Infrared Marker Improves Tissue Imaging

In biomedical imaging, molecular structures and processes can be visualized with fluorescent proteins. A newly developed method uses B cells of the immune system to produce fluorescent proteins with optimized properties. Depending on the light spectrum used and the organism under examination, these infrared markers can now deliver better-quality images. This novel technology can be used to optimize fluorescent markers for different imaging needs quickly and at low cost.

Ulrike Schoetz et al.: Usefulness of a Darwinian System in a Biotechnological Application: Evolution of Optical Window Fluorescent Protein Variants Under Selective Pressure. PLOS ONE 9 (2014) | doi: 10.1371/journal.pone.0107069

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Optimizing Gene Transfer

Lentiviruses are retroviruses which are used as gene vectors to transfer genes into cells. Thus, they can therefore be used in gene therapy to replace a defective gene. However, it is difficult to increase the efficiency of such treatment: The virus should specifically track the target cell, but the quantity of virus should be kept as small as possible. Researchers have now developed an adjuvant which enhances the efficiency of the virus transduction. Thus, the transfer into the target cells can be optimized without additional toxicity.

Ines Höfig et al:  Systematic Improvement of Lentivirus Transduction Protocols by Antibody Fragments Fused to VSV-G as Envelope Glycoprotein. Biomaterials 35/ 13 (2014) | doi: 10.1016/ j.biomaterials.2014.01.051

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Tracing Unique Cells with Mathematics

Each cell in the body is unique, even cells of the same tissue type are slightly different from each other. Scientists use single-cell mRNA analyses to investigate these heterogeneities. But they are laborious and expensive, and the handling of the single cells causes considerable inaccuracies. Scientists have now found a way to considerably improve single-cell analysis by applying methods of mathematical statistics.

Sameer S. Bajikar et al.: Parameterizing Cell-to-cell Regulatory Heterogeneities via Stochastic Transcriptional Profiles. PNAS 11 (2014) | doi: 10.1073/pnas.1311647111

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