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October 01 - October 31

10 entries found

Combining l..
Start date: October 05
11:00 am 12:00 pm



How a complex vascular network is established during development and remodelled in growing embryos has been difficult to analyse in the past due to the lack of appropriate model systems allowing at the same time high resolution live imaging and genetic dissection. Such analyses are possible in the zebrafish and I will report on progress made in the field to better understand the control of cell behaviour during the branching and remodelling process. To better dissect molecular players regulating cell behaviour, we are functionalizing protein binders to manipulate proteins directly and acutely during vascular morphogenesis. In the future, these novel tools should allow to dissect biological processes in much more detail in living organisms.

5 most recent papers

Junction-based lamellipodia drive endothelial cell rearrangements in vivo via a VE-cadherin-F-actin based oscillatory cell-cell interaction. Paatero I, Sauteur L, Lee M, Lagendijk AK, Heutschi D, Wiesner C, Guzmán C, Bieli D, Hogan BM, Affolter M, Belting HG. Nat Commun. 2018 Aug 31;9(1):3545.

Protein binders and their applications in developmental biology. Harmansa S, Affolter M. Development. 2018 Jan 26;145(2).

Cell behaviors and dynamics during angiogenesis. Betz C, Lenard A, Belting HG, Affolter M. Development. 2016 Jul 1;143(13):2249-60.

Endothelial cell self-fusion during vascular pruning. Lenard A, Daetwyler S, Betz C, Ellertsdottir E, Belting HG, Huisken J, Affolter M. PLoS Biol. 2015 Apr 17;13(4):e1002126.

In vivo analysis reveals a highly stereotypic morphogenetic pathway of vascular anastomosis. Lenard A, Ellertsdottir E, Herwig L, Krudewig A, Sauteur L, Belting HG, Affolter M. Dev Cell. 2013 Jun 10;25(5):492-506.

Assembly of..
Start date: October 11
04:00 pm 05:00 pm


A fundamental issue during brain development is the correct formation of connections. Accuracy of these events is critical for the correct function of the brain, including processes involved in memory, learning, perception and behaviour. My lab is interested in the molecular mechanisms underlying the assembly of the vertebrate visual circuitry. Our research mainly focuses on genes controlling synapse specificity between different subpopulations of retinal neurons, as well as long-range connections between the eye and retinorecipient areas. In addition, we are interested in how specific dendritic structures of retinal neurons generate visual functionalities.

5 most recent papers
Antinucci, P., Suleyman, O., Monfries, C. & Hindges, R. (2016). Neural Mechanisms Generating Orientation Selectivity in the Retina. Current Biology 26: 1802-1815.

Antinucci, P., Nikolaou, N., Meyer, M.P. & Hindges, R. (2013). Teneurin-3 specifies morphological and functional connectivity of retinal ganglion cells in the vertebrate visual system. Cell Reports 5: 582-592.

Maiorano N.A. & Hindges, R. (2013) Restricted perinatal retinal degeneration induces retina reshaping and correlated structural rearrangement of the retinotopic map, Nature Commun. 4:1938 doi: 10.1038/ncomms2926 (2013).

Pinter, R. & Hindges, R. (2010). Perturbations of MicroRNA Function in Mouse Dicer Mutants Produce Retinal Defects and Lead to Aberrant Axon Pathfinding at the Optic Chiasm, PLoS ONE 5(4): e10021.

Hindges, R., McLaughlin, T., Genoud, N., Henkemeyer, M. & O'Leary, D.D.M. (2002). EphB forward signaling controls directional branch extension and arborization required for dorsal-ventral retinotopic mapping. Neuron 35: 475-487.

Räumliches ..
Start date: October 17
10:00 am 11:30 am

Decoding li..
Start date: October 22
01:00 pm 02:00 pm


Cell fate control from multipotent progenitor cells of key importance to understanding organ formation, origins of congenital defects, and regeneration. We study the emergence of cardiovascular cell fates within the context of mesoderm patterning with cellular, molecular, and evolutionary approaches using zebrafish as principal model. We have uncovered gene-regulatory elements that reveal the developmental stages from earliest cardiovascular prongenitor formation to subsequent organ patterning. Decoding the upstream input for these regulatory elements, we uncovered an ancient molecular program that drives the formation of cardiovascular-competent mesoderm. Our approaches further instruct the discovery and mechanistic follow-up of genotype-phenotype associations in congential cardiovascular diseases.

5 most recent papers
1) Felker A, Prummel KD, Merks AM, Mickoleit M, Brombacher EC, Huisken J, Panáková D, Mosimann C. Continuous addition of progenitors forms the cardiac ventricle in zebrafish. Nat Commun. 2018 May 21;9(1):2001. doi: 10.1038/s41467-018-04402-6.

2) Cantù C, Felker A, Zimmerli D, Prummel KD, Cabello EM, Chiavacci E, et al.. Mutations in Bcl9 and Pygo genes cause congenital heart defects by tissue-specific perturbation of Wnt/beta-catenin signaling Genes Dev. accepted, in print.

3) Maximizing mutagenesis with solubilized CRISPR-Cas9 ribonucleoprotein complexes. Burger A, Lindsay H, Felker A, Hess C, Anders C, Chiavacci E, Zaugg J, Weber LM, Catena R, Jinek M, Robinson MD, Mosimann C. Development. 2016 Jun 1;143(11):2025-37. doi: 10.1242/dev.134809. Epub 2016 Apr 29.

4) Lindsay H, Burger A, Biyong B, Felker A, Hess C, Zaugg J, Chiavacci E, Anders C, Jinek M, Mosimann C, Robinson MD. CrispRVariants charts the mutation spectrum of genome engineering experiments. Nat Biotechnol. 2016 Jul 12;34(7):701-2. doi: 10.1038/nbt.3628.

5) Mosimann C, Panáková D, Werdich AA, Musso G, Burger A, et al. Chamber identity programs drive early functional partitioning of the heart. Nat Commun. 2015 Aug 26;6:8146. doi: 10.1038/ncomms9146.

Public Sele..
Start date: October 22
02:00 pm 06:00 pm


2:10 pm    Brüggemann, Dorothea "Nanobiophysics of cells“
2:40 pm    Fischer-Friedrich, Elisabeth "Structure and mechanics of living matter"
3:10 pm    Kayser, Jona “Evolution in dense cellular assemblies“
4:00 pm    Fouchard, Jonathan “Out-of-plane forces in cellular and tissular functions”
4:30 pm    Sabass, Benedikt “From molecules to micromechanics of cells and tissue”

Public Demo..
Start date: October 23
09:00 am 11:00 am


9:10 am   Sabass, Benedikt “Mechanisms of intrahost migration of parasites”
9:30 am   Kayser, Jona “Let’s start moving - The epithelial–mesenchymal transition”
9:50 am   Fouchard, Jonathan “Mammalian cells motility and the role of the mechanical environment”
10:20 am Fischer-Friedrich, Elisabeth "Running, tumbling and gliding - how bacteria move"
10:40 am Brüggemann, Dorothea “Mechanisms of cell motility - Muscle cell contraction“

Evolution o..
Start date: October 24
11:00 am 12:00 pm


Our group studies the evolution of primates. We are interested in the molecular forces that shape phenotypic differences between primate species. I am most fascinated by the differences in brain size and cognitive abilities. Our main focus is on the impact of Gene regulatory factors, such as transcription factors and non-coding RNAs, on differences in transcriptomes, gene regulatory networks, and ultimately the phenotype. We use computational and wet-lab methods to understand the evolution of human specific phenotypes.

5 most recent papers
Kutsche, L.K., Gysi, D.M.*, Fallmann, J., Lenk, K., Petri, R., Swiersy, A., Klapper, S.D., Pircs, K., Khattak, S., Stadler, P.F., Jakobsson, J., Nowick, K. and Busskamp, V. (2018) Combined experimental and system-level analyses reveal the complex regulatory network of miR-124 during human neurogenesis, Cell Systems in press (*my PhD student is shared first author)

Berto, S. and Nowick, K. (2018) Species-specific changes in a primate transcription factor network provide insights into the molecular evolution of the primate prefrontal cortex, Genome Biology and Evolution 2018 Jul 30. doi: 10.1093/gbe/evy149

Berto, S., Perdomo-Sabogal, A., Gerighausen, D., Qin, J., Nowick, K. (2016) A transcription factor consensus network of the human frontal lobe: insights into the molecular mechanisms of human cognitive abilities, Frontiers in Genetics: Special on Systems biology of transcriptional regulation

Perdomo-Sabogal, A., Nowick, K.*, Piccini, I., Sudbrak, R., Lehrach, H., Yaspo, ML., Warnatz, HJ.†, Querfurth, R.*† (2016) Human lineage-specific transcriptional regulation through GA binding protein transcription factor alpha (GABPa), Molecular Biology and Evolution 2016 May; 33(5):1231-44. doi: 10.1093/molbev/msw007 (*shared corresponding author)

Perdomo-Sabogal, A., Kanton, S., Walter, M.B.C., Nowick, K. (2014) The roles of gene regulatory factors in the history of human evolution, Current Opinion in Genetics and Development 9;29C: 60-67

Start date: October 25
04:00 pm 05:00 pm


The functions of proteins have traditionally been linked to their well-defined three-dimensional, folded structures. It is becoming increasingly clear, however, that many proteins perform essential functions without being folded. Single-molecule spectroscopy provides new opportunities for investigating the structure, dynamics, and interaction mechanisms of such unfolded or 'intrinsically disordered' proteins (IDPs). I will focus on a recent example of two IDPs that bind one another with very high affinity yet remain unstructured. This type of interaction has interesting ramifications for kinetic mechanisms of binding and cellular regulation.

5 most recent papers
Borgia, A., Borgia, M., Bugge, K., Kissling, V.M., Heidarsson, P.O., Fernandes, C.B., Sottini, A., Soranno, A., Buholzer, K., Nettels, D., Kragelund, B.B., Best, R.B., & Schuler, B. (2018) Extreme disorder in an ultra-high-affinity protein complex. Nature, 555, 61-66.

Zosel, F., Mercadante, D., Nettels, D. & Schuler, B. (2018) A proline switch explains kinetic heterogeneity in a coupled folding and binding reaction. Nat. Comm. 9:3332

Soranno, A., Holla, A., Dingfelder, F., Nettels, D., Makarov, D.E. & Schuler, B. (2017) Integrated view of internal friction in unfolded proteins from single-molecule FRET, contact quenching, theory, and simulations. Proc. Natl. Acad. Sci. USA 114, E1833-E1839.

Schuler, B. (2018) Perspective: Chain dynamics of unfolded and intrinsically disordered proteins from nanosecond fluorescence correlation spectroscopy combined with single-molecule FRET. J. Chem. Phys. 149, 010901

Schuler, B., Hofmann, H., Nettels, D. & Soranno, A. (2016) Single-molecule FRET spectroscopy and the polymer physics of unfolded and intrinsically disordered proteins. Annu. Rev. Biophys. 45, 207-231.

Start date: October 30
09:30 am 10:30 am


Chronic inflammation is a major risk factor for the development of several tumour types Inflammation acts as a double-edged sword: on one hand, it is a precise mechanism that allows proper response upon damage. However, when de-regulated or persistent, inflammation can promote tumour development. NR5A2 is indispensable for complete pancreatic acinar cell differentiation and homeostasis. SNPs in the vicinity of the NR5A2 locus have been associated with higher risk of developing pancreatic cancer. In this work, I have demonstrated that, in addition to its role in pancreas homeostasis, NR5A2 restrains an inflammatory program in the pancreas. In this regard, reduced NR5A2 expression both in normal mouse and human pancreas, leads to a basal pre-inflammatory state that resembles that one observed in the early stages of pancreatitis. During the pre-inflammatory state, NR5A2 is genomically relocated from the promoter of acinar differentiation genes to the promoter of inflammatory genes in a process that is dependent on AP-1 proteins. Our work opens the possibility of identifying scenarios of pre-inflammation in other tissues even when histology and functionality seems normal. In addition, I have drilled down into the tumour supressor role of NR5A2. I have found that the combination of mutant KRas activation and Nr5a2 heterozigosity in pancreatic epithelial cells leads to the formation of aggressive cystic lesions, in the absence of exogenous pancreatitis induction.

5 most recent papers
The molecular Basis of Radial Interacalation during Tissue Spreading in Early Development. András Szabó,1 Isidoro Cobo,1 Sharif Omara, Sophie McLachlan, Ray Keller, and Roberto Mayor,∗ 1 Equal contributors. Developmental Cell, 2016 May 9; 37(3): 213-225.

Nr5a2 couples differentiation and inflammation in the pancreas. Isidoro Cobo, Paola Martinelli, Marta Flández, Latifa Bakiri, Mingfeng Shang, Enrique Carrillo-de-Santa-Pau, Jinping Jia, Liv Themmesen, Torunn Bruland, Natalia del Pozo, Sara Olson, Jill Smith, William R. Bamlet, Gloria M Petersen, Núria Malats, Laufey T Amundadottir, Erwin F. Wagner and Francisco X Real. Nature, 2018. 554(7693):533-537.

c-Myc downregulation is required for preacinar to acinar maturation and pancreatic homeostasis. Victor J. Sánchez-Arévalo, Luis C. Fernandez, Enrique Carrillo-de-Santa-Pau, Laia Richart, Isidoro Cobo, Jerowslak Cendrowski, Ulises Moreno, Natalia del Pozo, Diego Megías, Bernardette Bréant, Cristopher Wright, Mark Magnuson and Francisco X. Real. Gut, 2016-312306.

Nr5a2 heterozygosity cooperates with KRas in the development of aggressive cystic tumours. Isidoro Cobo, Mar Iglesias, Marta Flández, Miriam Llorente, Natalia del Pozo and Francisco X. Real (manuscript in preparation).

Nfic is a novel Nr5a2 interactor and regulator of the acinar program. Isidoro Cobo, Julia Melia, Sumit Paliwal, Irene Millán, Fernando García, Javier Muñoz, Joo-Cheol Park and Francisco X. Real. (manuscript in preparation).

What signal..
Start date: October 30
04:00 pm 05:00 pm

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