Cell signalling & mitosis

deconvolved histone and wf EGFP — Marking the chromosomes (Green) and the nucleus (Magenta) with fluorescent tags allows us to monitor mitotic events in cultured cells

During the complex voyage of building tissues, cells integrate intrinsic factors, as well as extrinsic cues from their niches to modulate the progression, symmetry, orientation, and fate of their divisions. Misregulation of these processes is associated with loss of the cellular hierarchies, genome instability, and can ultimately lead to disease, notably cancer. We aim to unravel how different signalling pathways, including Wnt, shape the cell fate during mammalian development and tissue renewal by modulating cell division.

Related publication: Bufe et al, PNAS 2021

Wnt signalling in stem cell & cancer biology

The fate of adult stem cells is determined by the integration of extracellular signals released from their niches. For example, Wnt and R-spondin ligands are essential for stem cell maintenance and tissue homeostasis across many organs. We study the transduction of Wnt signals, notably in mammalian adult stem cells of the gut. We aim to identify and characterise signalling components, interactions and modifications that play key roles in stem cell renewal, and whose misregulation can lead to cancer.

Intestinal organoids.png — Intestinal stem cells cultured ex vivo form organoids shaped as the intestinal crypts. The organoids retain the cellular hierarchy of the original tissue.

Wnt signal transduction & crosstalk

NePCs in neurospheres — Neural progenitors self renew *ex vivo* in neurosphere cultures by integrating extracellular cues

The extracellular signalling pathways are notorious for their cross talk, but it is still not well understood how stem and progenitor cells integrate different extracellular signals from a multi-signalling niche to modulate their fate and behaviour. We aim to characterise the fundamental molecular hubs where the Wnt pathway and other signals converge, and uncover biological functions regulated by these mechanisms.

Cellular Recorders

New generation of molecular devices that allow cells to record in their DNA the amplitude and timeline of different biochemical events

We aim to develop novel modular DNA-based memory devices controlled by recombinases and Cas endonucleases to record complex and transient cellular events into permanent and readable genetic memories. We will use these molecular devices explore the long-term dynamics on mitotic and signal events across scales, from cells to organisms.

Collaborations

Prof. Holger Bastians – University Medical Center Göttingen (UMG)

Dr. Xabier Contreras – University of the Basque Country

Prof. Gislene Pereira – Heidelberg University

Dr. Bon-Kyoung Koo – Institute of Molecular Biotechnology (IMBA, Vienna)

Prof. Rocio Sotillo – DKFZ

Dr. Marina Mapelli – IEO Istituto Europeo di Oncologia

Dr. Josephine Bageritz – Heidelberg University

Dr. Chris Tape – UCL Cancer Institute

Prof. Andrei Chabes –Umeå University

Prof. Thomas W. Holstein – Heidelberg University

Dr. Petra Beli – Institute of Molecular Biology (IMB, Mainz)

Dr. Vanesa Fernandez Saiz – LMU

Prof. Thomas Worzfeld – Institute of Pharmacology, Marburg

Dr. Jan Ellenberg and Dr. Rainer Pepperkok – EMBL

Prof. Anna Marciniak – IWR/Bioquant

Funding