Researchers at the Hubrecht Institure study a variety of biological processes, mainly concerning the developmental biology of animals. Developmental biologists are interested in the mechanism by which an organism grows from a single fertilized egg into a fully formed adult. This encompasses many areas, from basic (pre-)embryonic processes, such as the establishment of a body plan, to the specifics of organ growth in adult animals. Closely linked to developmental biology is stem cell research. Embryonic, fetal, adult and cancer stem cells are all studied. Deregulation of developmental processes can lead to cancer, which is also a key theme of research within the institute. Knowledge and expertise gained within the Hubrecht will be beneficial for prevention and treatment of diseases and therefore for the quality of life.
Alexander van Oudenaarden firstname.lastname@example.org
Added value Hubrecht Institute for hDMT
The Hubrecht Institute performs basic research in the field of developmental biology, with an emphasis on the biology of stem cells. The institute aspires to be a world leader in this field. The institute currently ranks as one of top institutes worldwide in the field of developmental biology and stem cell research. This is reflected by the citation impact score of 2.86, which puts the Hubrecht at the top of the list of all institutes and universities in the Netherlands. Internationally, this score is also impressive and is comparable to the EMBL Heidelberg (2.98), Harvard (2.40), and MIT (2.45).
To maintain and improve this position we implement the following strategy:
• We use an international recruitment strategy focusing strictly on excellence.
• We have a tenure-track system for junior group leaders with a flat organizational structure; group leaders have full scientific freedom and receive all the positive and negative consequences of such responsibility. Currently approximately half of the junior group leaders receives tenure after 6 years. The evaluation procedure is transparant and is based on external referees.
• The institute is equipped with the most advanced equipment (microscopes, cell sorters, DNA sequencers) managed from a well-embedded facility support.
• We aim at increasing the critical mass of the institute by active national and international grant recruitment (including donations from foundations and wealthy individuals) and by closely collaborating with UMC Utrecht.
• We collaborate with the best national and international groups in the field of stem cell biology and developmental biology.
Expertise and facilities:
• Single-cell sequencing
• Organoid technology.
• Stem cells
• 4C, Hi-C technology
• Hubrecht Imaging facility
• Mouse facility
• FACS facility
• Media Kitchen
• Single-cell sequencing facility
Lgr5 stem cells, Wnt signaling & cancer
Originally focused on T lymphocyte transcription factors, we cloned Tcf1 in 1991. With the discovery that Tcf factors are the final effectors of Wnt signaling, we changed our interests to the biology of Wnt signaling in intestinal self-renewal and cancer. We identified a series of adult tissue stem cells with the novel Lgr5 marker and technologies for long-term culture of these stem cells as epithelial organoids, currently our major focus of research.
Group van Oudenaarden
Quantitative biology of development & stem cells
The van Oudenaarden lab is using a combination of experimental, computational, and theoretical approaches to quantitatively understand decision-making in single cells with a focus on questions in developmental and stem cell biology. We are particularly interested in how cells use gene networks to make robust decisions even in the presence of significant fluctuations in gene expression.
• Barker, N., van Es, J.H., Kuipers, J., Kujala, P., van den Born, M., Cozijnsen, M., Haegebarth,
A., Korving, J., Begthel, H., Peters, P.J., Clevers, H. Identification of stem cells in small
intestine and colon by marker gene Lgr5. Nature. 2007 Oct 25;449(7165):1003-7. Epub 2007
• Sato, T., van Es, J.H., Snippert, H.J., Stange, D.E., Vries, R.G., van den Born, M., Barker, N.,
Shroyer, N.F., van de Wetering, M., Clevers, H. Paneth cells constitute the niche for Lgr5 stem
cells in intestinal crypts. Nature. 2011 Jan 20;469(7330):415-8. doi: 10.1038/nature09637.
Epub 2010 Nov 28.
• Grün D, Kester L, van Oudenaarden A. Validation of noise models for single-cell
transcriptomics. Nat Methods. 2014 Jun;11(6):637-40. doi: 10.1038/nmeth.2930. Epub 2014
• Junker, J.P., van Oudenaarden, A. Every cell is special: genome-wide studies add a new
dimension to single-cell biology. Cell. 2014 Mar 27;157(1):8-11. doi: 10.1016/j.cell.2014.02.010.
• de Wit, E., Bouwman ,B.A., Zhu, Y., Klous, P., Splinter, E., Verstegen, M.J., Krijger, P.H.,
Festuccia, N., Nora, E.P., Welling, M., Heard, E., Geijsen, N., Poot, R.A., Chambers, I., de
Laat, W. The pluripotent genome in three dimensions is shaped around pluripotency factors.
Nature. 2013 Sep 12;501(7466):227-31. doi: 10.1038/nature12420. Epub 2013 Jul 24.
• Karthaus, W.R., Iaquinta, P.J., Drost, J., Gracanin, A., van Boxtel, R., Wongvipat, J., Dowling,
C.M., Gao, D., Begthel,H., Sachs, N., Vries, R.G., Cuppen, E., Chen, Y., Sawyers, C.L.,
Clevers, H.C. Identification of multipotent luminal progenitor cells in human prostate organoid
cultures. Cell. 2014 Sep 25;159(1):163-75.
• Junker, J.P., Noel, E.S., Guryev, V., Peterson, K.A., Shah, G., Huisken, J., McMahon, A.P.,
Berezikov, E., Bakkers, J. and van Oudenaarden,A. Genome-wide RNA tomography in the
zebrafish embryo Cell 159, 662 – 675 (2014).
• Ritsma, L., Ellenbroek, S.I.J., Zomer, A., Snippert, H.J., de Sauvage, F.J., Simons, B.D.,
Clevers, H., van Rheenen, J. Intestinal crypt homeostasis revealed at single-stem-cell level
by in vivo live imaging. Nature. 2014 Mar 20;507(7492):362-5.
• Stange, D.E., Koo, B.K., Huch, M., Sibbel, G., Basak, O., Lyubimova, A., Kujala, P., Bartfeld,
S., Koster, J., Geahlen, J.H., Peters, P.J., van Es, J.H., van de Wetering, M., Mills, J.C.,
Clevers, H. Differentiated Troy+ chief cells act as reserve stem cells to generate all lineages
of the stomach epithelium. Cell. 2013 Oct 10;155(2):357-68.
• Huch, M., Dorrell, C., Boj, S.F., van Es, J.H., Li, V.S., van de Wetering, M., Sato, T., Hamer, K.,
Sasaki, N., Finegold, M.J., Haft, A., Vries, R.G., Grompe, M., Clevers, H. In vitro expansion
of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature. 2013 Feb