Dorothee Childs presented her work at the EMBL-Wellcome Genome Campus Conference “Target Validation using Genomics and Informatics 2015″, which took place from 8th to 10th December 2015 in Cambridge.
More than 200 people attended this ground-breaking conference. Dorothee gave a talk on “Screening for drug targets in intact cells by thermal proteome profiling”, a project in which she is involved as part of a collaboration between EMBL Heidelberg and GSK’s SME Cellzome, which is also based in Heidelberg.”
Annika Gable has a B.Sc. in Molecular Biotechnology from the University of Heidelberg. She joined the Huber group in December 2015. At EMBL, she is finishing up her M.Sc. in Molecular Biotechnology (major: Bioinformatics) with a thesis on analyzing high-throughput chromatin conformation capture (Hi-C) data.
Abstract: We extended thermal proteome profiling to detect transmembrane protein–small molecule interactions in cultured human cells. When we assessed the effects of detergents on ATP-binding profiles, we observed shifts in denaturation temperature for ATP-binding transmembrane proteins. We also observed cellular thermal shifts in pervanadate-induced T cell–receptor signaling, delineating the membrane target CD45 and components of the downstream pathway, and with drugs affecting the transmembrane transporters ATP1A1 and MDR1.
Junyan has a PhD in Computational Biology and Drug Design from Shanghai Institute of Materia Medica, Chinese Academy of Sciences. His previous research focused on understanding mechanisms of drug response using integrated multi-omics technology and large scale ex-vivo drug testing approaches. In November 2015, he joined the Huber Group as a postdoctoral fellow and is now working on the SOUND project.
Mike joined EMBL in October 2015 as part of the de.NBI project where he is working on the development pipelines, workflows and computational approaches for large scale biological experiments. He has a PhD in computational biology from the University of Cambridge, UK.
Abstract: Studies on signalling dynamics in living embryos have been limited by a scarcity of in vivo reporters. Tandem fluorescent protein timers provide a generic method for detecting changes in protein population age and thus provide readouts for signalling events that lead to changes in protein stability or location. When imaged with quantitative dual-colour fluorescence microscopy, tandem timers offer detailed ‘snapshot’ readouts of signalling activity from subcellular to organismal scales, and therefore have the potential to revolutionize studies in developing embryos. Here we use computer modelling and embryo experiments to explore the behaviour of tandem timers in developing systems. We present a mathematical model of timer kinetics and provide software tools that will allow experimentalists to select the most appropriate timer designs for their biological question, and guide interpretation of the obtained readouts. Through the generation of a series of novel zebrafish reporter lines, we confirm experimentally that our quantitative model can accurately predict different timer responses in developing embryos and explain some less expected findings. For example, increasing the FRET efficiency of a tandem timer actually increases the ability of the timer to detect differences in protein half-life. Finally, while previous studies have used timers to monitor changes in protein turnover, our model shows that timers can also be used to facilitate the monitoring of gene expression kinetics in vivo.
Summary: Morphogenesis of multicellular organisms is driven by localized cell shape changes. How, and to what extent, changes in behavior in single cells or groups of cells influence neighboring cells and large-scale tissue remodeling remains an open question. Indeed, our understanding of multicellular dynamics is limited by the lack of methods allowing the modulation of cell behavior with high spatiotemporal precision. Here, we developed an optogenetic approach to achieve local modulation of cell contractility and used it to control morphogenetic movements during Drosophila embryogenesis. We show that local inhibition of apical constriction is sufficient to cause a global arrest of mesoderm invagination. By varying the spatial pattern of inhibition during invagination, we further demonstrate that coordinated contractile behavior responds to local tissue geometrical constraints. Together, these results show the efficacy of this optogenetic approach to dissect the interplay between cell-cell interaction, force transmission, and tissue geometry during complex morphogenetic processes.