Timothy Saunders

Major pet conference peeve - speakers not speaking to time. It shortens breaks, reduces chances to engage ECRs and sets a bad precedent. Typically the bigger the name, the worse the timing.

Fly embyro with cells labeled to show heart formation. The heart (cyan) forms from two distant regions of the embryo (far left). These regions migrate to the embryo midline, where they fuse into a tube to make the first heart structure (far right). Precise alignment and pairing of these cells are crucial for proper heart development.

Cells “speed date” to find their perfect neighbors when forming tissues. This marks a pivotal step in creating functional organs, like in this early heart development illustrated in a fly larvae.

Learn more: www.cell.com/biophysj/ful...

@timesaunders.bsky.social
@biophysj.bsky.social

👀 Looking for a Master Program in Physics of Life? Preferably free? Maybe in a collaborative and interdisciplinary environment? Check this out👇🏻

Nuclear speed and cycle length co-vary with local density during syncytial blastoderm formation in a cricket - Nature Communications Early in insect embryo development, many nuclei share one large cell, travel varied paths and self-organize into a single layer. Donoughe et al. illuminate this process with live-imaging, modeling, an...

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.

Aster repulsion drives short-ranged ordering in the Drosophila syncytial blastoderm Summary: The multinucleated embryo of the fruit fly D. melanogaster distributes nuclei with the help of centrosome-organised microtubule asters, with ordering dynamically adapting to synchronous nucle...

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.

Topological defects in epithelia govern cell death and extrusion - Nature By modelling epithelial cells as active nematic liquid crystals, stresses induced at the sites of topological defects are found to be the primary drivers of extrusion and cell death.

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...).

Geometry of gene regulatory dynamics | PNAS Embryonic development leads to the reproducible and ordered appearance of complexity from egg to adult. The successive differentiation of different...

There’s been exciting work recently linking ideas from topology to biological systems. This has ranged from bird flocking (www.pnas.org/doi/full/10....), to gene networks (www.pnas.org/doi/full/10....), and now how nuclei pack in the Drosophila blastocyst (www.nature.com/articles/s41...).

Enjoyed doing this interview. Hope it's helpful for a more general audience.

Latest lab paper is out :)

eur01.safelinks.protection.outlook.com?url=https%3A...

With Sham Tlili, we show that a surprisingly simple equilibrium physics model can explain the highly dynamic process of cell matching in the heart.

#ZebrafishMeeting featuring @nicolettapetridou.bsky.social & @rashmi-priya.bsky.social

Read about my amazing PhD student Ryan. Many thanks to CoB for hosting him for 3 months

A wonderful day. Thanks so much for the invitation

Decoding temporal interpretation of the morphogen Bicoid in the early Drosophila embryo Cell fates endowed by higher Bicoid concentration require input for longer duration, demonstrating a temporally non-linear morphogen-mediated pattern formation.

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.

Dev Mech 2024-25 logo

Since I have so many new friends 😄, I thought I'd advertise this. Together with @pritiagarwal.bsky.social and Lance Davidson, we run a Developmental Mechanics seminar series on Zoom (originally started by Ronen Zaidel-Bar). This coming Thursday, we have our last session for 2024. Join us!!

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)

The Gregor lab optimised fluorescent in situ hybridisation (PMID: 21390295) to reveal “>90% of all bicoid mRNA is continuously present within the anterior 20%.” They also concluded that Bicoid is rapidly removed in nuclear cycle 14, after patterning is set. (12/22)

Therefore, we see that up to 2010 there were still major questions regarding pretty much every part of how the Bicoid gradient formed, and this cast major doubts over the validity of the SDD model. (11/22).

Tweetorial continued -unable to post more on the previous one:
(ii) Bicoid could be produced in the oocyte, leading to early distribution of Bicoid (PMID: 28296637). (iii) Bicoid may not need to be degraded;dilution by nuclei could be sufficient to generate a gradient (PMID: 18001703) (10/22)

Therefore, we see that up to 2010 there were still major questions regarding pretty much every part of how the Bicoid gradient formed, and this cast major doubts over the validity of the SDD model. (11/22).

(ii) Bicoid could be produced in the oocyte, leading to early distribution of Bicoid (PMID: 28296637). (iii) If the diffusivity is small enough, then Bicoid may not need to be degraded; dilution by nuclei would be sufficient to generate a gradient on the relevant time scales (PMID: 18001703) (10/22)