Advanced Imaging Platform (AIP) https://heika-research.de/en/research/advanced-imaging-platform-aip en High-throughput selective cell isolation based on imprinted microfluidics and fluorescence microscopy https://heika-research.de/en/research/advanced-imaging-platform-aip/high-throughput-selective-cell-isolation-based-imprinted <span class="field field--name-title field--type-string field--label-hidden">High-throughput selective cell isolation based on imprinted microfluidics and fluorescence microscopy</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span lang="" about="/en/user/32" typeof="schema:Person" property="schema:name" datatype="">Regine Kleber</span></span> <span class="field field--name-created field--type-created field--label-hidden">Mon, 07/30/2018 - 13:11</span> <div class="field field--name-field-introduction-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-introduction-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <!--[if IE 9]><video style="display: none;"><![endif]--> <source srcset="/sites/default/files/styles/introduction_image_1x_desktop/public/2018-08/IMG_2025.JPG?h=71976bb4&amp;itok=CLlglwzw 1x, /sites/default/files/styles/introduction_image_2x_desktop/public/2018-08/IMG_2025.JPG?h=71976bb4&amp;itok=oQbfy3Xh 2x" media="all and (min-width: 769px)" type="image/jpeg"/> <source srcset="/sites/default/files/styles/introduction_image_1x_tablet/public/2018-08/IMG_2025.JPG?h=71976bb4&amp;itok=aH62sG0W 1x, /sites/default/files/styles/introduction_image_2x_tablet/public/2018-08/IMG_2025.JPG?h=71976bb4&amp;itok=v12a-_YN 2x" media="all and (min-width: 481px) and (max-width: 768px)" type="image/jpeg"/> <source srcset="/sites/default/files/styles/introduction_image_1x_phone/public/2018-08/IMG_2025.JPG?h=71976bb4&amp;itok=qLjkUPH2 1x, /sites/default/files/styles/introduction_image_2x_phone/public/2018-08/IMG_2025.JPG?h=71976bb4&amp;itok=48HTbpXQ 2x" media="all and (max-width: 480px)" type="image/jpeg"/> <!--[if IE 9]></video><![endif]--> <img src="/sites/default/files/styles/introduction_image_1x_desktop/public/2018-08/IMG_2025.JPG?h=71976bb4&amp;itok=CLlglwzw" alt="Presentation on HEiKA Day 2018" typeof="foaf:Image" /> </picture> </div> <div class="field field--name-field-copyright field--type-string field--label-visually_hidden"> <div class="field__label visually-hidden">Copyright</div> <div class="field__item">Heika</div> </div> </article> </div> <div class="clearfix text-formatted field field--name-field-summary field--type-text-long field--label-hidden field__item"><p>Functional analysis of biological samples for diagnostic or research purposes often requires the isolation of small cell populations from heterogeneous mixtures. Traditionally, this is accomplished using either flow cytometry or microdissection/manipulation performed using microscopes. Flow cytometry-based cell sorters provide unparalleled throughput, but the information output is very limited when it comes to subcellular organization and cellular structures. This information can be collected through cell sorting using microscopy-based cell enrichment methods. However, these methods lack the required throughput for the analysis of large, complex samples and usually require expensive equipment.<br /> In this interdisciplinary project, we aim to develop a fluorescence microscope with the ability to image and isolate highly parameterized subpopulations of phenotypic cell mixtures in real time. Cell imaging will be accomplished using roll-to-roll fabricated flexible microfluidic devices with an integrated cell immobilization mechanism for high throughput and high image resolution. The microfluidic chips will be designed, fabricated, and tested in house. Selective cell isolation will be achieved by directing a high energy laser beam onto cells exhibiting an unwanted phenotype, killing them, and thereby removing them from the pool. The remaining subpopulation of cells will be collected alive for further propagation and analysis. This process will be completely automated and repeated as many times as necessary using the same microfluidic device until the desired cell population has been isolated.<br /> This cell isolation microscope will be developed and tested in the context of basic cell biology, but the impact of the successful development of such a system is expected to extend far beyond basic research into applications such as drug development and cancer research. </p> </div> <div class="field field--name-field-research-bridges field--type-entity-reference field--label-above"> <div class="field__label">Research bridges</div> <div class="field__items"> <div class="field__item"><a href="/en/research/advanced-imaging-platform-aip" hreflang="en">Advanced Imaging Platform (AIP)</a></div> </div> </div> <div class="field field--name-field-start-date field--type-datetime field--label-above"> <div class="field__label">Start date</div> <div class="field__item"> <time datetime="2018-01-01T12:00:00Z" class="datetime">01/01/2018</time> </div> </div> <div class="field field--name-field-end-date field--type-datetime field--label-hidden field__item"><time datetime="2018-12-31T12:00:00Z" class="datetime">12/31/2018</time> </div> <div class="field field--name-field-contact-person field--type-entity-reference field--label-above"> <div class="field__label"><h3>Project management</h3></div> <div class="field__items"> <article data-history-node-id="75" role="article" about="/en/dr-iordania-constantinou" class="node node--type-people-profile node--view-mode-teaser"> <div class="node__content"> <div class="content-container"> <div class="header-container"> <h2> <a href="/en/dr-iordania-constantinou" rel="bookmark"><span class="field field--name-title field--type-string field--label-hidden">Dr. Iordania Constantinou</span> </a> </h2> </div> <div class="field field--name-field-institute field--type-string field--label-hidden field__item">Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH)</div> <div class="field field--name-field-facility field--type-string field--label-hidden field__item">Heidelberg University</div> <div class="field field--name-field-link field--type-link field--label-hidden field__item"><a href="https://www.zmbh.uni-heidelberg.de/Knop/staff.html">Knop Lab @ ZMBH</a></div> </div> </div> </article> <article data-history-node-id="76" role="article" about="/en/dr-dario-mager" class="node node--type-people-profile node--view-mode-teaser"> <div class="node__content"> <div class="content-container"> <div class="header-container"> <h2> <a href="/en/dr-dario-mager" rel="bookmark"><span class="field field--name-title field--type-string field--label-hidden">Dr. Dario Mager</span> </a> </h2> </div> <div class="field field--name-field-institute field--type-string field--label-hidden field__item">Institute of Microstructure Technology (IMT)</div> <div class="field field--name-field-facility field--type-string field--label-hidden field__item">Karlsruhe Institute of Technolgoy</div> <div class="field field--name-field-link field--type-link field--label-hidden field__item"><a href="https://www.imt.kit.edu/mager.php">Mager Group</a></div> </div> </div> </article> </div> </div> Mon, 30 Jul 2018 11:11:01 +0000 Regine Kleber 77 at https://heika-research.de Synthesis of single cell, single molecule RNA probes for the detection of enogenous microRNAs in human cancer to dentify metastatically relevant cance cell fractions in heterogenous tumors https://heika-research.de/en/research/advanced-imaging-platform-aip/synthesis-single-cell-single-molecule-rna-probes-detection <span class="field field--name-title field--type-string field--label-hidden">Synthesis of single cell, single molecule RNA probes for the detection of enogenous microRNAs in human cancer to dentify metastatically relevant cance cell fractions in heterogenous tumors</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span lang="" about="/en/user/32" typeof="schema:Person" property="schema:name" datatype="">Regine Kleber</span></span> <span class="field field--name-created field--type-created field--label-hidden">Mon, 07/30/2018 - 13:16</span> <div class="clearfix text-formatted field field--name-field-summary field--type-text-long field--label-hidden field__item"><p>Cancer metastasis is the major cause of death of cancer patients, and novel diagnostic methods are urgently needed to prevent metastasis. Especially, methods are needed to identify metastatically critical cells within the heterogeneity of diverse cells in patients’ primary tumors, to predict which patient, despite an initial curative treatment, would need additional (targeted) therapy to prevent metastasis. Our recent work has characterized the most critical microRNAs for metastasis in a systematic approach at resected metastasis tissues, and we have already succeeded in introducing the first single cell, single molecule laser superresolution microscopy to visualize specific microRNA molecules marked with photostable cyanine-styryl dyes in subcellular compartments (including exosomes) of fixed single cells in vitro in tumour cell lines. Own work and publications of others have confirmed the importance of the action of particular pro-metastatic miRs in exosomes, which can communicate a cross-talk between cancer and surrounding cells, and also helps cancer cells to prime the metastatic niche in distant organ compartments. Also, the differential interaction of miRs with different 3’UTR targets, depending on a specific cellular context, might be able to support, or inhibit, a pro-metastatic phenotype in a given cell.<br /> The aim of our project therefore is to attempt to synthesize, develop and establish, for the first time, a single cell, single molecule superresolution protocol able to detect, and visualize, 1) naturally occurring miRs in single cells by sequence-specific fluorescence nucleic acid “light up” probes 2) Naturally occurring miRs in single living cells and 3) miRs within single cells of tissue sections of primary tumors of patients. We also will try to attempt multicolour protocols by using differently labelled nucleic acid probes to visualize microRNA intracellular patterns critical for metastasis. </p> </div> <div class="field field--name-field-research-bridges field--type-entity-reference field--label-above"> <div class="field__label">Research bridges</div> <div class="field__items"> <div class="field__item"><a href="/en/research/advanced-imaging-platform-aip" hreflang="en">Advanced Imaging Platform (AIP)</a></div> <div class="field__item"><a href="/en/research/synthetic-biology-sb" hreflang="en">Synthetic Biology (SB)</a></div> </div> </div> <div class="field field--name-field-start-date field--type-datetime field--label-above"> <div class="field__label">Start date</div> <div class="field__item"> <time datetime="2018-01-01T12:00:00Z" class="datetime">01/01/2018</time> </div> </div> <div class="field field--name-field-end-date field--type-datetime field--label-hidden field__item"><time datetime="2018-12-31T12:00:00Z" class="datetime">12/31/2018</time> </div> <div class="field field--name-field-contact-person field--type-entity-reference field--label-above"> <div class="field__label"><h3>Project management</h3></div> <div class="field__items"> <article data-history-node-id="78" role="article" about="/en/prof-dr-heike-allgayer" class="node node--type-people-profile node--view-mode-teaser"> <div class="node__content"> <div class="content-container"> <div class="header-container"> <h2> <a href="/en/prof-dr-heike-allgayer" rel="bookmark"><span class="field field--name-title field--type-string field--label-hidden">Prof. Dr. Heike Allgayer</span> </a> </h2> </div> <div class="field field--name-field-institute field--type-string field--label-hidden field__item">Medical Faculty Mannheim </div> <div class="field field--name-field-facility field--type-string field--label-hidden field__item">Heidelberg University</div> <div class="field field--name-field-link field--type-link field--label-hidden field__item"><a href="https://www.umm.uni-heidelberg.de/inst/exp_chir/index_e.html">Experimental Surgery, Cancer Metastasis </a></div> </div> </div> </article> <article data-history-node-id="79" role="article" about="/en/prof-dr-hans-achim-wagenknecht" class="node node--type-people-profile node--view-mode-teaser"> <div class="node__content"> <div class="content-container"> <div class="header-container"> <h2> <a href="/en/prof-dr-hans-achim-wagenknecht" rel="bookmark"><span class="field field--name-title field--type-string field--label-hidden">Prof. Dr. Hans-Achim Wagenknecht</span> </a> </h2> </div> <div class="field field--name-field-institute field--type-string field--label-hidden field__item">Institute for Organic Chemistry </div> <div class="field field--name-field-facility field--type-string field--label-hidden field__item">Karlsruhe Institute of Technolgoy</div> <div class="field field--name-field-link field--type-link field--label-hidden field__item"><a href="http://www.ioc.kit.edu/wagenknecht/26.php">Wagenknecht Group</a></div> </div> </div> </article> </div> </div> Mon, 30 Jul 2018 11:16:37 +0000 Regine Kleber 80 at https://heika-research.de In vitro and in vivo Monitoring of Dopamine Levels in Neural Tissues using Novel Zeolite-based Chemosensors https://heika-research.de/en/research/advanced-imaging-platform-aip/vitro-and-vivo-monitoring-dopamine-levels-neural-tissues <span class="field field--name-title field--type-string field--label-hidden">In vitro and in vivo Monitoring of Dopamine Levels in Neural Tissues using Novel Zeolite-based Chemosensors</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span lang="" about="/en/user/32" typeof="schema:Person" property="schema:name" datatype="">Regine Kleber</span></span> <span class="field field--name-created field--type-created field--label-hidden">Mon, 11/12/2018 - 17:00</span> <div class="clearfix text-formatted field field--name-field-summary field--type-text-long field--label-hidden field__item"><p><span><span><span><span><span lang="EN-US" xml:lang="EN-US" xml:lang="EN-US">We propose the application of artificial neurotransmitter receptors (ANR) for the monitoring of dopamine levels in neuronal tissues as well as in prefrontal cortex and basal nuclei of intact mice. In the first step, existing and newly prepared fluorescent ANRs will be tested under the conditions of 2-photon microscopy and single photon microendoscopic imaging. Parameters that will be changed are the zeolite and dye identity, dye loading, surface functionalization and the size of the zeolites. Kinetic rates of signal appearance, which is related to the neurotransmitter uptake rates, will be measured. Additional ANRs will be prepared that contain widely used 2-photon absorbing dyes such as DAPI, either directly as the “indicator dye” or as the “antenna dye” (in combination with FRET to the indicator dye). The sensing performance of such ANRs for different aromatic amine neurotransmitters will be evaluated in buffers and biological media (e.g. cell culture media). Promising ANR candidates will be then tested first by application to acute brain slices using single-photon and two-photon excitation. To image dopamine signalling in the intact brain, ANRs will be directly delivered to the brain region of interest by stereotaxic injection.</span></span></span></span></span></p> <p><span lang="EN-US" xml:lang="EN-US" xml:lang="EN-US"><span><span>Regions of the prefrontal cortex accessible to two-photon microscopy will be examined with in vivo two-photon microscopy. Deep regions such as the striatum or nucleus accumbens will be imaged via implanted microendoscopes using either two-photon imaging in head-fixed mice or single-photon imaging with miniature microscopes in freely behaving mice. This approach promises systemic readouts of dopamine action in the context of the behaving animal, allowing to directly link neuronal and circuit mechanisms related to dopamine signalling with distinct behaviours.</span></span></span></p></div> <div class="field field--name-field-research-bridges field--type-entity-reference field--label-above"> <div class="field__label">Research bridges</div> <div class="field__items"> <div class="field__item"><a href="/en/research/advanced-imaging-platform-aip" hreflang="en">Advanced Imaging Platform (AIP)</a></div> </div> </div> <div class="field field--name-field-start-date field--type-datetime field--label-above"> <div class="field__label">Start date</div> <div class="field__item"> <time datetime="2019-01-01T12:00:00Z" class="datetime">01/01/2019</time> </div> </div> <div class="field field--name-field-end-date field--type-datetime field--label-hidden field__item"><time datetime="2019-12-31T12:00:00Z" class="datetime">12/31/2019</time> </div> <div class="field field--name-field-contact-person field--type-entity-reference field--label-above"> <div class="field__label"><h3>Project management</h3></div> <div class="field__items"> <article data-history-node-id="192" role="article" about="/en/prof-dr-thomas-kuner" class="node node--type-people-profile node--view-mode-teaser"> <div class="node__content"> <div class="content-container"> <div class="header-container"> <h2> <a href="/en/prof-dr-thomas-kuner" rel="bookmark"><span class="field field--name-title field--type-string field--label-hidden">Prof. Dr. Thomas Kuner</span> </a> </h2> </div> <div class="field field--name-field-institute field--type-string field--label-hidden field__item">Institute for Anatomy and Cell Biology</div> <div class="field field--name-field-facility field--type-string field--label-hidden field__item">Heidelberg University</div> <div class="field field--name-field-link field--type-link field--label-hidden field__item"><a href="http://www.ana.uni-heidelberg.de/index.php?id=ag-kuner">Kuner Group</a></div> </div> </div> </article> <article data-history-node-id="193" role="article" about="/en/dr-frank-biedermann" class="node node--type-people-profile node--view-mode-teaser"> <div class="node__content"> <div class="content-container"> <div class="header-container"> <h2> <a href="/en/dr-frank-biedermann" rel="bookmark"><span class="field field--name-title field--type-string field--label-hidden">Dr. Frank Biedermann</span> </a> </h2> </div> <div class="field field--name-field-institute field--type-string field--label-hidden field__item">Institute of Nanotechnology</div> <div class="field field--name-field-facility field--type-string field--label-hidden field__item">Karlsruhe Institute of Technolgoy</div> <div class="field field--name-field-link field--type-link field--label-hidden field__item"><a href="https://www.int.kit.edu/staff_2034.php">Research Group Biedermann</a></div> </div> </div> </article> </div> </div> Mon, 12 Nov 2018 16:00:21 +0000 Regine Kleber 207 at https://heika-research.de Modular shining architectures for cellular imaging https://heika-research.de/en/research/advanced-imaging-platform-aip/modular-shining-architectures-cellular-imaging <span class="field field--name-title field--type-string field--label-hidden">Modular shining architectures for cellular imaging</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span lang="" about="/en/user/32" typeof="schema:Person" property="schema:name" datatype="">Regine Kleber</span></span> <span class="field field--name-created field--type-created field--label-hidden">Mon, 11/12/2018 - 17:06</span> <div class="clearfix text-formatted field field--name-field-summary field--type-text-long field--label-hidden field__item"><p><span><span><span><span><span lang="EN-US" xml:lang="EN-US" xml:lang="EN-US">In this project, we will design and develop a modular approach to address target-specifically accumulating conjugates consisting of bright fluorescent dyes and target-affine peptides. For this, we will create fluorescent dyes with bright fluorescence in the optimal optical imaging window (targeting the IR range) and derivatize them with functional groups to obtain substances which can be efficiently introduced in various bioactive molecules such as - but not limited to - receptor-affine peptides. On the other side, we will synthesize receptor-specific peptides being able to efficiently address our model receptor system (gastrin-releasing peptide receptor) and chemically modify them to achieve a high stability and appropriate hydrophilicity (depending on the respective fluorescent dye used) to obtain fluorescent drugs with high potential for prospective in vivo imaging.</span></span></span></span></span></p> <p><span><span><span><span><span lang="EN-US" xml:lang="EN-US" xml:lang="EN-US">For this purpose, chemical developments have to be carried out to establish an approach yielding substances with high future potential. The developed model ligands will be characterized regarding their optical properties as well as their hydrophilicity and in vitro stability.</span></span></span></span></span></p> <p><span><span><span><span><span lang="EN-US" xml:lang="EN-US" xml:lang="EN-US">This project complements the activities of the Bräse group within the GRK 2939 - the Wängler group has profound expertise in particular in in vitro evaluations and tumor mouse models which is not present in this depth in the GRK.</span></span></span></span></span></p> <p><span lang="EN-US" xml:lang="EN-US" xml:lang="EN-US"><span><span>In addition, the Wängler group adds radiochemistry expertise lacking in Karlsruhe and its GRK.</span></span></span></p></div> <div class="field field--name-field-research-bridges field--type-entity-reference field--label-above"> <div class="field__label">Research bridges</div> <div class="field__items"> <div class="field__item"><a href="/en/research/advanced-imaging-platform-aip" hreflang="en">Advanced Imaging Platform (AIP)</a></div> <div class="field__item"><a href="/en/research/synthetic-biology-sb" hreflang="en">Synthetic Biology (SB)</a></div> </div> </div> <div class="field field--name-field-start-date field--type-datetime field--label-above"> <div class="field__label">Start date</div> <div class="field__item"> <time datetime="2019-01-01T12:00:00Z" class="datetime">01/01/2019</time> </div> </div> <div class="field field--name-field-end-date field--type-datetime field--label-hidden field__item"><time datetime="2019-12-31T12:00:00Z" class="datetime">12/31/2019</time> </div> <div class="field field--name-field-contact-person field--type-entity-reference field--label-above"> <div class="field__label"><h3>Project management</h3></div> <div class="field__items"> <article data-history-node-id="194" role="article" about="/en/prof-dr-carmen-wangler" class="node node--type-people-profile node--view-mode-teaser"> <div class="node__content"> <div class="content-container"> <div class="header-container"> <h2> <a href="/en/prof-dr-carmen-wangler" rel="bookmark"><span class="field field--name-title field--type-string field--label-hidden">Prof. Dr. Carmen Wängler</span> </a> </h2> </div> <div class="field field--name-field-institute field--type-string field--label-hidden field__item">Institut für Klinische Radiologie und Nuklearmedizin</div> <div class="field field--name-field-facility field--type-string field--label-hidden field__item">Heidelberg University</div> <div class="field field--name-field-link field--type-link field--label-hidden field__item"><a href="https://www.umm.uni-heidelberg.de/inst/radchem/Mitarbeiter_Waengler_Carmen.html">CV Carmen Wängler</a></div> </div> </div> </article> <article data-history-node-id="82" role="article" about="/index.php/en/prof-dr-stefan-brase" class="node node--type-people-profile node--view-mode-teaser"> <div class="node__content"> <div class="field field--name-field-profile-picture field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-portrait-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <!--[if IE 9]><video style="display: none;"><![endif]--> <source srcset="/sites/default/files/styles/portrait_1x_tablet/public/2018-07/BD_member_SBraese.jpg?h=e6a3be71&amp;itok=6QuZdlcq 1x, /sites/default/files/styles/portrait_2x_tablet/public/2018-07/BD_member_SBraese.jpg?h=e6a3be71&amp;itok=dCT6rQg1 2x" media="all and (min-width: 769px)" type="image/jpeg"/> <source srcset="/sites/default/files/styles/portrait_1x_tablet/public/2018-07/BD_member_SBraese.jpg?h=e6a3be71&amp;itok=6QuZdlcq 1x, /sites/default/files/styles/portrait_2x_tablet/public/2018-07/BD_member_SBraese.jpg?h=e6a3be71&amp;itok=dCT6rQg1 2x" media="all and (min-width: 481px) and (max-width: 768px)" type="image/jpeg"/> <source srcset="/sites/default/files/styles/portrait_1x_phone/public/2018-07/BD_member_SBraese.jpg?h=e6a3be71&amp;itok=Fo3LUysR 1x, /sites/default/files/styles/portrait_1x_tablet/public/2018-07/BD_member_SBraese.jpg?h=e6a3be71&amp;itok=6QuZdlcq 2x" media="all and (max-width: 480px)" type="image/jpeg"/> <!--[if IE 9]></video><![endif]--> <img src="/sites/default/files/styles/portrait_1x_tablet/public/2018-07/BD_member_SBraese.jpg?h=e6a3be71&amp;itok=6QuZdlcq" alt="Prof. Dr. Stefan Braese" typeof="foaf:Image" /> </picture> </div> </article> </div> <div class="content-container"> <div class="header-container"> <h2> <a href="/index.php/en/prof-dr-stefan-brase" rel="bookmark"><span class="field field--name-title field--type-string field--label-hidden">Prof. Dr. Stefan Bräse</span> </a> </h2> </div> <div class="field field--name-field-function-1 field--type-string field--label-hidden field__item">Director Research Bridge SB</div> <div class="field field--name-field-institute field--type-string field--label-hidden field__item">Institute of Organic Chemistry (IOC)</div> <div class="field field--name-field-facility field--type-string field--label-hidden field__item">Karlsruhe Institute of Technolgoy</div> <div class="field field--name-field-link field--type-link field--label-hidden field__item"><a href="http://www.ioc.kit.edu/braese/english/26.php">Research Group Bräse</a></div> </div> </div> </article> </div> </div> Mon, 12 Nov 2018 16:06:46 +0000 Regine Kleber 208 at https://heika-research.de