Synthetic Biology (SB) https://heika-research.de/en/research/synthetic-biology-sb en 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 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 Modulation of epithelial-to-mesenchymal transition (EMT) with small molecules https://heika-research.de/en/research/synthetic-biology-sb/modulation-epithelial-mesenchymal-transition-emt-small-molecules <span class="field field--name-title field--type-string field--label-hidden">Modulation of epithelial-to-mesenchymal transition (EMT) with small molecules</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 - 17:17</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-GB" xml:lang="EN-GB" xml:lang="EN-GB">EMT is a widespread and important biological process that relies on a genetically induced reduction of coordinated cell behavior. This reduction allows individual cells inside an epithelium to change their properties (i.e. enhanced migratory capacity, invasiveness, elevated resistance to apoptosis, and increased production of extracellular matrix components) and leave it as individual, mesenchymal cells. Understanding the regulation of cell behavior during EMT is crucial for understanding core developmental processes like muscle and heart development, and it has recently become a focus in the investigation of new strategies against cancer and cancer resistance.</span></span></span></span></span></p> <p><span><span><span><span><span lang="EN-GB" xml:lang="EN-GB" xml:lang="EN-GB">The Lemke lab has identified two extreme modes of EMT-related processes in the midge C. riparius and the fruit fly D. melanogaster. In Chironomus, levels of cell coordination were low: future muscle cells leave the epithelium and translocate to the inside of the embryo using canonical EMT. In Drosophila, levels of cell coordination were high and EMT was delayed: cells remained in an epithelium, collectively folded into the inside of the embryo, and only then gradually separated. Genetic investigations have shown that two genes act as a switch to evoke canonical EMT in Drosophila, and delayed EMT in Chironomus, rendering this pair of species as an in vivo test tube to reveal factors that are necessary and/or sufficient to strengthen epithelial integrity and suppress EMT. To identify factors beyond the known genetic players, we will identify and investigate small molecules that trigger changes in cell and tissue behavior. The initial compounds will be obtained by natural product isolation and selection of promising core structures from the ComPlat library. By comparing genetic with compound-induced changes, the mechanism of EMT suppression will be further dissected. More generally, we aim to identify previously proposed but still unknown biological targets that regulate the coordination of cell behavior.</span></span></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/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="203" role="article" about="/en/jun-prof-dr-steffen-lemke" 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/jun-prof-dr-steffen-lemke" rel="bookmark"><span class="field field--name-title field--type-string field--label-hidden">Jun.-Prof. Dr. Steffen Lemke</span> </a> </h2> </div> <div class="field field--name-field-institute field--type-string field--label-hidden field__item">Centre for Organismal Studies Heidelberg (COS)</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.cos.uni-heidelberg.de/index.php/s.lemke?l=_e">Junior Research Group Lemke</a></div> </div> </div> </article> <article data-history-node-id="204" role="article" about="/en/dr-nicole-jung" 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-nicole-jung" rel="bookmark"><span class="field field--name-title field--type-string field--label-hidden">Dr. Nicole Jung</span> </a> </h2> </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.complat.kit.edu/26.php">ComPlat @KIT</a></div> </div> </div> </article> </div> </div> Mon, 12 Nov 2018 16:17:19 +0000 Regine Kleber 213 at https://heika-research.de 3D bioprinting of a blood-retina-barrier to elucidate the role of mesenchymal stromal/stem cells as potential therapy in diabetic retinopathy (3D-BRB) https://heika-research.de/en/research/synthetic-biology-sb/3d-bioprinting-blood-retina-barrier-elucidate-role-mesenchymal <span class="field field--name-title field--type-string field--label-hidden">3D bioprinting of a blood-retina-barrier to elucidate the role of mesenchymal stromal/stem cells as potential therapy in diabetic retinopathy (3D-BRB)</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 - 17:18</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-GB" xml:lang="EN-GB" xml:lang="EN-GB">Pericyte loss is the earliest morphological sign of diabetic retinopathy. During the course of the disease the retinal blood vessels face a loss in the stabilizing pericytes which leads to destabilization of the blood vessel, haemorrhage, and due to local hypoxia to the angiogenesis of new capillaries leading to blindness. It has been hypothesized that diabetic retinopathy can be delayed or prevented through restoration of pericytes and pericyte function by adipose tissue-derived stem/stromal cells (ASC). According to surface and internal marker validation, ASCs share pericyte characteristics, and may have a therapeutic benefit in injured micro vessels in the eye. In combination with endothelial cells (ECs), ASCs are able to establish functional vessels in vivo. However, the factors that coordinate EC-ASC communications to promote migration of these cells toward one another, and their heterotypic assembly into vascular structures are not well defined. To understand the mechanisms of EC-ASC interaction, we will team up to develop a sophisticated in vitro 3D model by 3D bio printing of retinal blood vessels from EC in which the migration and homing and differentiation of the ASCs can be monitored over a long period of time. There are preclinical data that prove the homing of ASCs towards these blood vessels when injected intravitreally. Eventually they migrate, adhere to and interact with EC, differentiate to take over the function of the formerly lost pericytes. We would like to understand, what are the secreted or presented factors of the EC-layer or other involved cells responsible for homing of ASCs and how the interact with the endothelium affects pericyte-like differentiation and subsequently control of endothelial cells. In addition the 3D systems offers a unique chance to study the influence of ASC/pericyte-like ASC on additional cell types, especially immune and inflammatory cells such as regulatory T cells and microglia in the context of diabetic retinopathy.</span></span></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/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="205" role="article" about="/en/prof-dr-karen-bieback" 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-karen-bieback" rel="bookmark"><span class="field field--name-title field--type-string field--label-hidden">Prof. Dr. Karen Bieback</span> </a> </h2> </div> <div class="field field--name-field-institute field--type-string field--label-hidden field__item">Medical Faculty Mannheim / Experimental Cell Therapy</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/transfusionsmedizin-und-immunologie/forschung/ag-bieback/">Research Group Bieback</a></div> </div> </div> </article> <article data-history-node-id="206" role="article" about="/en/prof-dr-ute-schepers" 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-ute-schepers" rel="bookmark"><span class="field field--name-title field--type-string field--label-hidden">Prof. Dr. Ute Schepers</span> </a> </h2> </div> <div class="field field--name-field-institute field--type-string field--label-hidden field__item">Institute of Toxicology and Genetics (ITG)</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.itg.kit.edu/schepers/index.php">Research Group Schepers</a></div> </div> </div> </article> </div> </div> Mon, 12 Nov 2018 16:18:40 +0000 Regine Kleber 214 at https://heika-research.de