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Toby Andrews Profile
Toby Andrews

@tobyandrews

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Developmental Biologist | Postdoc @TheCrick Organ Morphodynamics Laboratory | PhD @Cambridge_Uni | Form, Development, Evolution

London, UK
Joined June 2016
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@tobyandrews
Toby Andrews
1 year
Pumped to share our latest and first (!) work from @_Priya_R lab @TheCrick! Using the powers of #zebrafish, we uncover how multiscale mechanochemical coupling drives morphological and functional maturation of the developing heart 🫀. Stay tuned for the🧵 .
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@tobyandrews
Toby Andrews
10 months
RT @Dev_journal: Morphogens in the evolution of size, shape and patterning. In this Review, Lewis Mosby, Amy Bowen and @z_hvas @TheCrick @U….
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Toby Andrews
1 year
RT @IntSocDevBiol: Fantastic imaging! Check out Toby's preprint on heart mechanobiology.
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Toby Andrews
1 year
RT @jake_cs_: It was a lot of fun collaborating with @tobyandrews @_Priya_R on modelling mechanisms of organ-scale stretch. Check out Toby’….
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Toby Andrews
1 year
@jake_cs_ @mc_mcramel @Kirti_Guptatifr @briscoejames @_Priya_R @CALM_STP And get in touch with any questions, we'd love to hear what you think!.
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Toby Andrews
1 year
Big thanks and congrats to all authors, @jake_cs_ @mc_mcramel @Kirti_Guptatifr @briscoejames @_Priya_R, plus @CALM_STP, and the Crick aquatics team 🐟🐟🐟.
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Toby Andrews
1 year
Broadly, our study provides key insight into a fundamental problem – how organs are built with the right shape, size and function during embryonic development🫁🧠🫀📏 (11/11).
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Toby Andrews
1 year
All in all, we find that integration of multiscale mechanochemical cues tunes trabecular density to boost cardiac contractile force 💪, and expands heart size for improved blood filling capacity. The result is a functional beating heart 🫀 (10/11).
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Toby Andrews
1 year
. and improves their functional efficiency (9/11)
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Toby Andrews
1 year
To test our model predictions, we developed a nifty genetic tool to specifically dampen actomyosin tension in compact layer cells, allowing them to stretch. Amazingly, our approach makes hearts bigger.
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Toby Andrews
1 year
@jake_cs_ found tissue stretch occurs in a non-linear manner, at a tipping point when a critical fraction of cells (~40%) has activated Notch and dampened actomyosin tension. This behaviour enables robust tissue growth in response to small changes in input signals (8/11)
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Toby Andrews
1 year
But then, how do variable cellular properties yield reproducible changes in organ shape, size and function? 🤔 . We teamed up with @jake_cs_ to answer this question using a 3D vertex model (7/11)
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Toby Andrews
1 year
So, what remodels actomyosin? Not forces or cell shape changes. Instead, it's Notch, which is activated in a variable pattern in a small fraction of cells (6/11)
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Toby Andrews
1 year
Zooming in 🔬, stretched cells dampen their actomyosin tension. This allows them to undergo radical shape changes that increase heart size - a clever strategy to enable organ growth in the absence of significant proliferation (5/11)
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Toby Andrews
1 year
Using some cool morphometrics 📏, we find that as ridges grow, the outer compact layer cells stretch in response to organ-scale forces. Turns out, this blocks their further recruitment, thus stabilizing trabecular density in a self-organising manner⚖️ (4/11)
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Toby Andrews
1 year
Using lineage tracing, we find trabecular ridges don't grow through cell division . Instead, ridges grow by recruiting surrounding compact layer cells, which allows the heart to beat better and harder (3/11)
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@tobyandrews
Toby Andrews
1 year
As the embryo grows, the heart expands in size and forms two layers – an outer compact layer that defines heart shape and size, and an inner layer of multicellular muscular trabecular ridges – aka the force generating machinery (2/11)
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Toby Andrews
1 year
In zebrafish, we can watch hearts develop and beat in real time 👀 (1/11)
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@tobyandrews
Toby Andrews
1 year
RT @_Priya_R: We are recruiting! Fully funded post-doctoral positions are available. Interested in #morphogenesis #imaging #zebrafish? Join….
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Toby Andrews
1 year
How do embryos build organs with the right shape, size and function to keep our bodies ticking?🫀🫁👀. @_Priya_R and I give our take here, in a rollercoaster ride from local cell behaviors to organ-scale physiology and back .
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