AboutThis is the 6th ZOO meeting since 1993. The ZOO meeting series has become a landmark event in the field of cell adhesion and migration due to unique theme selection, high scientific profile with excellent speakers and limited number of attendees ( < 200).
The themes address molecular cell biological principles in the fields of cancer and immunology, with focus on cell-tissue interaction, migration and cell-cell communication. The speakers are leaders in their field and all make extensive use of imaging in their research. Scientific sessions will offer the latest developments in mechanobiology, leukocyte trafficking and cancer cell invasion. Live cell confocal imaging, super resolution imaging, quantitative imaging using innovative approaches and biosensors and computational modelling will be highlighted as part of the presentations.
The meeting will be organized in the Rotterdam Zoo conference facilities.
Photo: Wilbert Boelens.
Anna Akhmanova Utrecht UniversityAnna Akhmanova's group studies cytoskeletal organization and trafficking processes, which contribute to cell polarization, differentiation, vertebrate development and human disease. They are interested in understanding, at a systems level, how different aspects of cell architecture are coordinated.
Anna Akhmanova is a recipient of the ALW Vernieuwingsimpuls VIDI in 2001 and VICI awards in 2007, an ERC Synergy grant in 2013, and Spinoza Prize in 2018.
Jason Cyster University of CaliforniaThe major goals of the Cysterlab are (i) Decipher the guidance cue codes controlling leukocyte migration and interaction events during tissue surveillance and immune responses; (ii) Visualize immune response dynamics using advanced imaging approaches; (iii) Define the selection mechanisms for antibody affinity maturation and that help prevent autoantibody production.
Jason Cyster is currently the recipient of an HHMI Investigator Award and 2 NIH grants.
- Ansel KM, Ngo VN, Hyman PL, Luther SA, Forster R, Sedgwick JD, Browning JL, Lipp M, Cyster JG. 2000. A chemokine-driven positive feedback loop organizes lymphoid follicles. Nature 406:309- 314.
- Matloubian M, Lo CG, Cinamon G, Lesneski MJ, Xu Y, Brinkmann V, Allende ML, Proia RL, Cyster JG. 2004. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 427:355-360.
- Schwab SR, Pereira JP, Matloubian M, Xu Y, Huang Y, Cyster JG. 2005. Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients. Science 309:1735- 1739.
- Allen CD, Okada T, Tang HL, Cyster JG. 2007. Imaging of Germinal Center Selection Events During Affinity Maturation. Science 315:528-531
- Pereira, J.P., Kelly, L.M., Xu, Y. and Cyster, J.G. 2009. EBI2 mediates B cell segregation between the outer and center follicle. Nature 460
- Arnon TI, Xu Y, Lo C, Pham T, An J, Coughlin S, Dorn GW, Cyster JG. 2011. GRK2-dependent S1PR1 desensitization is required for lymphocytes to overcome their attraction to blood. Science 333:1898-1903.
- Muppidi JR, Schmitz R, Green JA, Xiao W, Larsen AB, Braun SE, An J, Xu Y, Rosenwald A, Ott G, Gascoyne RD, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Vaidehi N, Staudt LM, Cyster JG. Loss of signalling via Gα13 in germinal centre B-cell-derived lymphoma. Nature 2014; 516:254-258
Reinhold Förster Hannover Medical SchoolThe working group headed by Prof. Förster sees to the clarification of the cellular and molecular mechanisms forming the basis of the functional organisation of the lymphoid organs. We are particularly interested in clearing up the function of chemokines and chemokine receptors during the migration of immune cells into the secondary lymphoid organs and within these organs.
Reinhold Förster received many grants among SFB grants, DFG grant and an ERC advanced grant in 2013.
Jacco van Rheenen Netherlands Cancer InstituteBy intravital microscopy, the van Rheenen group studies the identity, behavior, and fate of cells that drive tumor initiation, progression, metastasis and the development of therapy resistance.
For his work Jacco van Rheenen received several international awards including the Stem Cells Young Investigator Award, ERC consolidator grant, and the Dr. Josef Steiner Cancer Research Foundation Award.
- Scheele CL, Hannezo E, Zomer A, Langedijk NSM, Simons BD, van Rheenen J, (2017) Identification of mammary stem cells and their dynamics during branching morphogenesis, Nature, 542(7641):313-317.
- Hannezo E, Scheele CLGJ, Moad M, Drogo N, Heer R, Sampogna RV, van Rheenen J#, Simons BD# (2017) A Unifying Theory of Branching Morphogenesis, Cell, Sep 21;171(1):242-255.e27. #co-senior
- Zomer A, Maynard C, Verweij FJ, Kamermans A, Schäfer R, Beerling E, Schiffelers RM, de Wit E, Berenguer J, Ellenbroek SIJ, Wurdinger T, Pegtel DM, van Rheenen J, (2015) In vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior, Cell, 161(5):1046-1057.
- Ritsma L, Ellenbroek SIJ, Zomer A, Snippert HJ, de Sauvage FJ, Simons BD, Clevers H, van Rheenen J, (2014) Intestinal crypt homeostasis revealed at single stem cell level by in vivo live-imaging, Nature, 507(7492):362-365.
Abstracts speakersAnna Akhmanova, Cell Biology, Faculty of Science, Utrecht University, The Netherlands
Control of cell morphology and migration by dynamic microtubules
Microtubules are dynamic polymers that can switch between phases of growth and shortening. This process, termed dynamic instability, is regulated by numerous cellular factors and can be affected by drugs used for cancer therapy. We found that mesenchymal cells embedded in a three-dimensional matrix become immobilized when microtubule growth is attenuated by drugs or due to the lack of specific regulatory factors. Such cells cannot form elongated protrusions and penetrate the matrix, and as a result, cancer cells with perturbed interphase microtubule growth are impaired in forming invasive tumors in mice. To uncover the underlying molecular mechanisms, we have reconstituted some essential properties of microtubule growth regulation in vitro using purified components.
Jason Cyster, HHMI and University of California, San Francisco, USA
Molecular cues controlling cell migration during the B cell response
Germinal centers (GCs) are important sites of antibody diversification and affinity improvement as well as lymphomagenesis. GC B cells are highly motile and this permits their surveillance for antigen and encounter with helper T cells. Despite this motility, GC B cells are tightly confined to the germinal center structure. Our work has identified a role for Ga13-coupled migration-inhibitory receptors in GC B cell confinement. This talk will give an overview of our studies on cell migration in GCs as well as detailing our latest findings on the molecular cues and mechanisms promoting GC B cell confinement.
Andy Ewald, Johns Hopkins University School of Medicine
E-cadherin is an invasion suppressor, survival factor, and metastasis promoter across multiple models of breast cancer
E-cadherin (E-cad) mediates adhesion and is considered a metastasis suppressor. However, invasive ductal breast cancers (IDC) retain E-cad in both primary tumors and metastases. To resolve this discrepancy, we tested the requirement for E-cad in three models of IDC. Loss of E-cad increased invasion but also reduced cancer cell proliferation, survival, circulating tumor cell number, tumor cell seeding, and metastasis formation. Transcriptionally, loss of E-cad was associated with increased TGF-ß, reactive oxygen, and apoptosis signaling. Disseminating E-cad-negative cells exhibited nuclear enrichment of SMAD2/3, oxidative stress, and apoptosis. Colony formation of E-cad-negative cells was rescued by treatment with TGF-ß receptor inhibitors, N-acetyl cysteine, or apoptosis inhibitors. These results suggest that E-cad can act as a survival factor during the detachment, systemic dissemination, and seeding phases of metastasis by limiting reactive oxygen-mediated apoptosis.
Louis Hodgson, Albert Einstein College of Medicine, New York, USA, Michael F. Price Center, New York, USA
New Windows on Living Cells: Spatiotemporal dynamics of Rho GTPases regulate cancer invasion
P21 Rho family small GTPases are critically important in many disease processes including cancer, inflammatory diseases, and developmental defects. This class of signaling molecules is critical in these diseases by impacting directly: cell polarity, motility and migration through their actions on downstream cytoskeleton/adhesion dynamics. Rho GTPases regulate these processes by coordinating, in both space and time, their activities in response to various environmental cues. However it has been difficult to dissect the coordinated dynamics by conventional approaches. Here, I will introduce several new biosensors specifically targeting different isoforms of Rho GTPases useful for live-cell imaging, based on Förster resonance energy transfer (FRET) that we have developed in our laboratory.
Kairbaan Hodivala-Dilke, Barts Cancer Institute, Queen Mary University of London
Cancer stroma modifications and the control of cancer growth
Our laboratory research aims to unravel the complex intercellular regulation of cancer growth via the inherent cross talk between cells within the tumour microenvironment and malignant cells. Using a combination of in vivo cancer models, stromal specific genetic ablation, proteomics, transcriptomics and metabolomics we dissect the molecular controllers of cancer growth. We exploit these discoveries to develop improved methods of cancer control and chemosensitivity. My talk will detail an example of current findings.
Sussan Nourshargh, William Harvey Research Institute, Barts and The London Medical School, Queen Mary University of London
Neutrophil breaching of venular walls: Mode, dynamics & mechanisms
Neutrophil migration into tissues forms a fundamental arm of innate immunity but is also a key instigator of numerous inflammatory disorders. Despite our increased knowledge of this process, there remain many open questions. Our group aims to decipher the mechanisms through which neutrophils breach venular walls, applying high resolution confocal intravital microscopy to analysis of neutrophil-endothelial cell and neutrophil-pericyte interactions in vivo. Our work has shed light on the mode and dynamics of such fundamental responses and identified key molecular players. Furthermore, we have discovered numerous disrupted modes of neutrophil transendothelial cell migration (TEM) that could have pathological implications. Principal concepts will be discussed.
Jacco van Rheenen, Department of Molecular Pathology, Oncode Institute, Netherlands Cancer Institute
Amsterdam, the Netherlands
Intravital microscopy revealed cancer stem cell plasticity to be important for metastasis
Although histological techniques have provided important information on stem cells and cancer, they draw static images of dynamic processes. To study dynamic processes, we have developed intravital microscropy techniques to monitor these cells in real time in living animals. We have used these techniques to study the identity and (migratory) behavior of (cancer) stem cells during pubertal mammary morphogenesis, during tumor growth, and during the metastatic process. Our IVM experiments illustrate that cellular properties and fate of (cancer) stem cells are highly dynamic, and that stemness is a state as opposed to an intrinsic property of a cell.
Martin Schwartz, Yale Cardiovascular Research Center
Force transmission and mechanotransduction through integrins.
Xavier Trepat, ICREA @ Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain, Barcelona Institute for Science and Technology (BIST), Barcelona, Spain
Mechanobiology of epithelial migration, growth and folding
Biological processes such as morphogenesis, tissue regeneration, and cancer invasion are driven by collective migration, division, and folding of epithelial tissues. Each of these functions is tightly regulated by mechanochemical networks and ultimately driven by physical forces. I will present maps of cell-cell and cell-extracellular matrix (ECM) forces during cell migration and division in a variety of epithelial models, from the expanding MDCK cluster to the regenerating zebrafish epicardium. These maps revealed that migration and division in growing tissues are jointly regulated. I will also present direct measurements of epithelial traction, tension, and luminal pressure in three-dimensional epithelia of controlled size and shape. By examining epithelial tension over time-scales of hours and for nominal strains reaching 1000%, we establish a remarkable degree of tensional homeostasis mediated by superelastic behavior.
Linda Le Noble