Of course, biology likes to be complicated. The above work generally takes the microtubule interaction between nuclei to be repulsive - but this doesn’t have to be the case (www.nature.com/articles/s41...). Future work will hopefully reveal how general these principles are.

With Ivo Telley, we have looked at packing of nuclei in ex vivo systems (journals.biologists.com/dev/article/..., elifesciences.org/articles/90541). It’s exciting to see how quantitative measurements reveal deeper insight into how biological systems reliably generate complex form from simple rules.

Such topological behaviour has also been shown to potentially play a role in cell extrusion (www.nature.com/articles/nat...). I wrote a short commentary on this, which is hopefully accessible for the more general audience (www.nature.com/articles/s41...).

A wonderful day. Thanks so much for the invitation

Hi Joachim. Can you add me - we do optogenetics ( elifesciences.org/articles/26258), laser ablation (www.cell.com/current-biol... and any quantitative tools we can use in fish and flies.

Just discovering how clunky Bluesky is for this :(

Our collaborators - the Weil lab - primarily focused on the first question. They revealed that localisation of bicoid mRNA localisation to P bodies inhibits translation. Chemically releasing bicoid from the P bodies resulted in translation in the oocyte…

We generated a Bicoid::Suntag reporter line. Importantly, this could address two important questions: (i) is bicoid translated in the oocyte, and if not, what is regulating this process?; (ii) where and when is bicoid translated in the embryo? (20)

We were motivated by the development of SunTag (PMID: 25307933), especially its application to the living Drosophila embryo by the Mounia lab (PMID: 33927056). (19)

It has remained an open question as to precisely when and where bicoid mRNA is translated. If bicoid mRNA is not translated in the oocyte, what is the mechanism? This motivated us to revisit the “S” part of the SDD model. (18/22)

These direct measures of motion reveal that the “diffusive” part of the SDD model needs adaptation (e.g., spatial and temporal change), but Bicoid does move through the embryo sufficiently fast to generate a gradient. (18/22)

With Thorsten Wohland, we used FCS at multiple locations and time points on Bicoid. We demonstrated different rates of diffusivity in the anterior and posterior regions (PMID: 38345326). (17/22)

However, these measurements were essentially averaging over the whole system – what is happening with Bicoid at more local (e.g., within a nuclear domain) scales? (16/22)

While all the models proposed can generate an exponentially-decaying profile, they all made different predictions for how old Bicoid would be at different locations. Only the SDD model was consistent with the overall behaviour of the protein age. (15/22)

During my post-doc and into my own lab we developed a Bicoid-timer reporter. By tagging Bicoid with two fluorescent proteins with different folding rates, we could effectively measure the age (i.e., ratio of the two fluorophore signals) of Bicoid at different locations (PMID: 30181144). (14/22)

Fluorescence correlation spectroscopy (FCS) of Bicoid::eGFP revealed that the dynamics were more complicated than inferred from FRAP. In particular, an effective diffusion coefficient of around 7um2s-1 (PMID: 20712981). This measurement was more in line with expectations from the SDD model. (13/22)