van Amerongen Lab - Developmental, Stem Cell & Cancer Biology

New pre-print: Quantitative live cell imaging of WNT/CTNNB1 signaling dynamics

We are really excited to announce that we just posted a new pre-print on Biorxiv

PhD student Saskia de Man is first author on (and very much the driving force behind) this story, which combines CRISPR/Cas9-mediated genome editing in haploid cells, with quantitative live-cell imaging and computational modeling. This work is a collaboration with Mark Hink and Gooitzen Zwanenburg, both also from the Swammerdam Institute for Life Sciences (SILS).

Using CRISPR/Cas9, Saskia generated a scarless knock-in of SGFP2 into the endogenous CTNNB1 locus, resulting in the expression of a fully functional fluorescent CTNNB1 fusion protein. By using haploid cells, we ensured that all tagging events were homozygous. She then performed quantitative microscopy analysis using confocal time-lapse imaging, fluorescence correlation spectroscopy and number & brightness analysis to investigate the different functional pools of CTNNB1 in the cytoplasm and nucleus in the absence and presence of a WNT stimulus.

Check out the paper if you want to know all about the distribution of CTNNB1 across a fast diffusing, monomeric pool and a slow diffusing complex-associated pool, or if you are curious about the first ever in cellulo measurements of the absolute concentration of CTNNB1 in each of these different fractions, which we have also used to build a computational model for WNT/CTNNB1 signaling that reveals three critical nodes of regulation in our favorite signal transduction pathway. And there are really pretty movies too!



Congratulations to Saskia on this fine piece of work, which cost blood, sweat and multiple years. The feedback we got at the 2019 Gordon Research Conference on WNT signaling has really inspired us to whip this story into it’s final shape and we are happy that it is now ready to meet the world.

28 May, 2020

Playing with Science

ARTEZ students Iris Beek and Moritz Brill presented the outcome of their residency at Filip Studios in Arnhem, where they worked on the case study "Playing with Science", for which Renée was the case holder.

As always, it was inspiring and informative to witness how artists approach a scientific question, with exciting potential for future developments (of the project and the collaboration).


image by Iris Beek and Moritz Brill

21 May, 2020

Comment in Bionieuws

Renée was featured in the latest issue of Bionieuws, where she was asked to comment on a recent paper by Caleb Dawson and colleagues from the lab of Jane Visvader. The paper describes the discovery and characterization of a population of macrophages (a specific type of immune cell) in the mammary gland. What is really cool is that you can see this population sandwiched in between the basal and luminal epithelial cells of the mammary epithelium.

It is always really nice to be able to provide some background, context and perspective for journalists and the broader public. In this case, it also meant doing a bit of background reading and discovering two related papers published by the labs of Felicity Davis and Christine Watson.
Thanks to the author, Nina Wubben, for making sure that this is a balanced piece that also does not over promise an immediate therapeutic benefit of this basic finding.

The piece (in Dutch) is pasted below.

Those interested in the details should check out the following papers:
Dawson et al. (2020), Nature Cell Biology: https://doi.org/10.1038/s41556-020-0505-0
Hitchcock et al. (2020). The FEBS Journal: doi:10.1111/febs.15126
Stewart et al. (2019), Frontiers in Cell and Developmental Biology: doi: 10.3389/fcell.2019.00250

16 May, 2020

Did you catch the easter egg?

The April 30 issue of Cell is out, which means that the perspective that Renée wrote in honor of Roel Nusse winning one of the 2020 International Gairder Awards is now officially published.

Did you catch the easter egg that is hidden in the figure?



WNT proteins are morphogens, which means that they are produced by specific cells and then diffuse (i.e. dilute) as they spread in the nearby surroundings. This spreading occurs in a gradient. As a result, cells that are closer or further removed from the source are exposed to different concentrations of WNT proteins and they are also wired to respond (i.e. activate specific genes) differently to specific concentrations of the protein.
In the textbook, this principle is typically depicted as the "French Flag model" (with blue, white and red zones depicting zones of low, medium and high concentrations of the morphogen). For the occasion, Renée and Tanne (who drew the figure) changed this into a "Dutch Flag model". It still looks the same and just required a bit of tweaking: changing the order to red, white and blue and adding a dash of orange - the Dutch national color- on top.

May this model live long and prosper!

1 May, 2020

Blog post on collaboration between artists and scientists

Renée was featured on the LSE impact blog in a post titled "To drive innovation, scientists should open their doors to more equitable relations with the arts". Written by Paige Jarreau, the piece highlights the unexpected spin offs that can occur from collaborations between artists and scientists.

30 April, 2020

Lab life in times of the COVID-19 pandemic

Like everyone else on the planet, we are dealing with the effects of the COVID-19 pandemic as best as we can. We went into work-from-home mode on 16 March with only a few critical experiments continuing and are staying in touch via Zoom (for group meetings) and Skype (for 1-on-1 meetings).

The most important thing right now is that everybody tries to stay healthy and sane as we are mostly cooped up inside to #FlattenTheCurve.
Working from home under these conditions is definitely not your average working-from-home day where you can quietly focus and concentrate on the work at hand. The news and a surreal "new normal" are a constant distraction - as are the questions and uncertainties about how all of this is affecting the progress of PhD trajectories.

Two new internships students, Femke and Zino, joined our lab for their BSc and MSc internships earlier this year. Their practical training was brutally interrupted, but official arrangements are now in place from the Biomedical Sciences program to deal with this situation. Femke is developing some CellProfiler skills under the supervision of Tanne using an existing dataset from Saskia and Zino is interrupting his internship on Wnt reporters in 3D organoid cultures under the supervision of Yorick to first write his literature thesis.

So far, everyone else has also made great efforts to be as productive as possible under the circumstances. Renee is still making her way through the original to do list and is finding out that Zoom meetings are much more tiring than meeting people in person. Larissa, Saskia, Tanne and Yorick are all writing drafts of papers/reviews/thesis chapters. While everyone can keep themselves busy for a couple of weeks in this way, we have also begun thinking about how we can potentially pick up our experimental work again in the longer term.

Hang in there everyone!


Our 2020 lab picture is a screenshot from one of our zoom meetings

9 April, 2020

New pre-print

We are happy to share a pre-print describing the generation and characterization of the first mouse model we built in the lab. Read it here.

Former PhD student Anoeska van de Moosdijk and current PhD student Yorick van de Grift are joint first authors, with other important contributions by PhD student Saskia de Man and technician Amber Zeeman. This work was funded by a 2015 grant from KWF Kankerbestrijding/Alpe d’HuZes. With a special thanks to the patient advocate on the interview selection committee who understood and supported the basic research that is required for long-term progress and stepwise innovation as we try to build better models for cancer research.

For those interested in the details: We generated a new 3’ knock-in in the Axin2 locus to allow both direct visualization (3xNLS-SGFP2 reporter) and lineage tracing (using a doxycycline inducible rtTA3) of WNT/CTNNB1 responsive cells. The strain can be combined with a tetO- and/or lineage-tracing reporter of interest. We are in the process of submitting this strain to an international repository so we can share it as broadly and quickly as possible with the rest of the scientific community.

4 April, 2020

Essay on the contributions of Roel Nusse to the Wnt signaling field

Today it was announced that Roel Nusse is one of the winners of the 2020 Gairdner Award. In honor of his contributions to the field of Wnt signaling and its broader implications in cancer and stem cell biology, Renée wrote an invited essay for Cell.
Thanks to Tanne for designing the figure!

The piece is available as Open Access publication here and can also be downloaded as a PDF file here.

31 March, 2020

NWO Grant awarded

Renée was awarded a Klein1 grant in the NWO open competition. Using a combination of quantitative live cell imaging and fluorescent tagging of endogenous Wnt pathway components, we hope to achieve a better understanding of the central working mechanism of the WNT/CTNNB1 pathway.

This is the first funding we got for this new line of research in the lab, thanks in large part to all of the preliminary data that were carefully collected by Saskia over the past few years, in close collaboration with Mark Hink.

See the Dutch abstract below from the NWO website:.

26 March, 2020

Short review on WNT/CTNNB1 signaling in breast cancer

We published a short review article on the role of WNT/CTNNB1 signaling in human breast cancer in Frontiers in Cell and Developmental Biology, as part of the special topic on mammary gland biology (edited by Dr. Zuzana Koledova from Masryk University).

The review article was inspired by and based on an MSc literature thesis, written by Emma van Schie (who is first author on the paper). The best outcome of research based teaching! It also helped Renée organize her thoughts on the current knowledge gaps in the field.

2 February, 2020

First publication of 2020

We published our first paper in 2020! Previously out as a pre-print on BioRxiv we are happy that our study about the interaction between TMEM98 and FRAT2 found a peer-reviewed home in Plos One.

First author Tanne van der Wal just started her PhD in October, and this is earlier work from her BSc internship. Taking old data from Renée that had been accumulating since 2004, we wrapped up the characterization of the trafficking of this transmembrane protein and verified that 15 years after the start of this project across town at the Netherlands Cancer Institute this transmembrane protein still modulates FRAT2 protein levels, thereby reducing WNT/CTNNB1 signaling activity.

It was a nice bonus to see Figure 2 from the paper being highlighted on Twitter for #FluorescenceFriday.

24 January, 2020

Lecture about genome editing

On Monday evening 13 January, Renée gave a lecture for members and guests of the "Chemische Kring" (society of chemists) in Rotterdam about the ins and outs of gene editing. The lecture hall at the "Hogeschool Rotterdam" was filled with an exciting mixture of chemists, biologists (including some students who came to attend after working with CRISPR/Cas in the lab themselves) and the occasional philosopher.



We talked about bacterial immune systems, CRISPR babies and the history of cutting and pasting with DNA. Hopefully there was enough depth for the chemists and not too much detail for the less molecularly inclined!

13 January, 2020

NEMO Kinderlezing

Renee gave the last NEMO Kinderlezing of 2019 . This time the topic was aging. A lot of 8-12 year olds came to the NEMO Studio Theater and together we went searching for an answer to the question: "How old can I get?"

That took us on a journey deep inside our bodies, where we peaked into the cells to figure out how cells know what to do, to see how the DNA and mitochondria work, and to discover how little mistakes and malfunctions in these microscopically small components contribute to aging. We also talked about extending life span, and how new techniques like cutting-and-repairing our DNA might one day prevent us from getting old or sick.
But this crowd was not fooled very easily and the morning lecture essentially ended with a philosophical question from one of the younger kids: Why do we want to live forever? Can we just not accept the fact that life has an end to it? This was followed by a sobering conclusion from the first row that even if we were able to extend life into all eternity, the universe itself has a final lifespan. On that note, we all had a look at some cells under the microscope and went home. A little bit older, but also a little bit wiser.

Thanks to all the kids for asking such interesting questions, for offering your perspective and for making me need all of my science fiction and space knowledge to keep up with you! And of course thanks to everyone at NEMO and FNWI communication for the awesome help in prepping for this audience.


image credit: Marion Vetter

15 December, 2019

ENBDC Think Tank in Manchester

Renee travelled to Manchester, where she met up with the rest of the ENBDC organizing committee for a peptide hydrogel workshop (thanks to everyone involved!) and a full day talking about research gaps in breast (cancer) biology.


image credit: Leander Blaas (via Twitter).

Thank you to Rob Clarke for running such an entertaining and smoothly organized Think Tank and for taking us out to dinner in a former cotton exchange on the UK election evening to drown any Brexit-related sorrow in good conversation.

12 December, 2019

Seminar in Aberdeen

Renee gave a talk at the University of Aberdeen, the third oldest university in Scotland. She got to talk about science with loads of different and interesting people all day, which is always a bonus. Thank you to Stefan Hoppler for the invitation and for making this such an enjoyable visit, including the sampling of the local pub food and Indian cuisine!

28 November, 2019

Master class for artists and designers

Renee gave a masterclass for artists and designers at Filip Studios in Arnhem on pattern formation in biology and the molecular processes that normally take place unseen inside our cells.
It was good to meet up with Roos Meerman again, with whom the lab previously collaborated as part of the BioArt and Design Award competition. Thanks also to Sabine Winters for organizing this residency program and for the invitation!

12 November, 2019

Seminar by Jeroen van Zon

Jeroen van Zon, group leader on Quantitative Developmental Biology at AMOLF, visited us from just across the street to give a talk about his work on worms and intestinal organoids. A great example of how biology and physics can be combined to yield new insights about how cell division and differentiation are controlled to guide the development and maintenance of complex animal tissues.

8 November, 2019

Nika presents our work in Chicago

Nika presented her work at the Cell Symposium on Transcriptional Regulation in Evolution, Development and Disease in Chicago. She got good feedback on her work on Wnt gene regulation (a joint effort with Katrin and Yorick), which means that now it is on to writing the PhD thesis!

20 October, 2019

Keynote lecture at the Finnish Developmental Biology Society and Stem Cell Network meeting

Renee gave a keynote lecture at the Finnish Developmental Biology Society and Stem Cell Network during their annual retreat just outside of Helsinki. The awesome opening keynote by Josh Brickman was a tough act to follow... It was great to interact and hang out with so many stem cell and developmental biology aficionados for a couple of days. Very impressed by the cool science that is going on in Finland!



Thanks to Marja Mikkola, who turned out to be an excellent tour guide in addition to a developmental biologist, Renee also caught a glimpse of Helsinki on Saturday.

11 October, 2019

Outreach lecture

High school teachers and their students visited the University of Amsterdam for lectures and a behind-the-scenes tour of some of our labs and facilities. Renée gave a talk on the basic science behind stem cell biology and regenerative medicine.

2 October, 2019

Tanne has joined the lab as a new PhD student

On 1 October Tanne van der Wal started her PhD thesis research in the group. She will be dissecting the molecular mechanisms of WNT/CTNNB1 signaling using CRISPR/Cas9 mediated tagging and functional imaging.

1 October, 2019

Poster prize for Saskia de Man at the 2019 GRC on Wnt signalling

Saskia and Renée attended the 2019 GRC on Wnt signaling in Vermont.

Preceding the GRC, Saskia attended the GRS, where she chaired one of the sessions. Renée also chaired a session at the GRC, organised the power hour and gave a talk highlighting the lab’s ongoing work on Wnt gene regulation and functional imaging of Wnt signal transduction. Saskia presented her work in one of the GRC poster sessions and, as icing on the cake, won one of the poster prizes.



Saskia receives one of the poster prizes. photo credit: Arial Zeng

It was a great and interactive meeting and we return to the lab invigorated with lots of great feedback and new ideas.
The next Wnt meeting will take place in September 2020 in Japan. The Wnt meeting will return as a GRC meeting in 2021 and 2023 (location to be announced) and rumor has it that the 2022 Wnt meeting may be held in China or Singapore.

16 August, 2019

Veni grant for Katrin Wiese

We are very excited to announce that Katrin Wiese was awarded a Veni grant from NWO (the Dutch Science Foundation). This competitive personal grant allows Katrin to further develop her ideas on Wnt gene regulation and to zoom in on the molecular processes involved for the coming three years.

Congratulations Katrin!

15 July, 2019

Lab lunch

The Bsc students are wrapping up their internships, so the lab went for lunch at De Polder. Goodbye Beau, Delano and Kyah. Thanks for all your hard work and contributions and good luck in your future endeavors!

10 July, 2019

Travel grants for Nika Heijmans and Saskia de Man

Both Nika Heijmans and Saskia de Man were awarded travel grants from the Amsterdams Universiteitsfonds and the Genootschap ter Bevordering van Natuur-, Genees- en Heelkunde.
Thanks to these grants, Nika will be able to present her PhD work at the Cell Symposium on Transcriptional Regulation in Evolution, Development and Disease in Chicago in October and Saskia will present her PhD project at the 2019 GRS and GRC on Wnt signaling in Vermont in August.

1 July, 2019

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