Our latest from
@briscoejames
lab: How temporal & spatial pattering cues are integrated in the vertebrate neural tube to organise cell type generation during development.
Our latest: What controls the pace of embryonic development?
Human motor neurons differentiate 2.5X slower than mouse
Not due to differences in signalling or regulatory elements
Human proteome 2X more stable than mouse & explains tempo difference
I’m delighted & honoured to be elected a Fellow of the Royal Society
@royalsociety
Thank you to friends, colleagues & mentors for support over the years
Most importantly, to all lab members, past and present. It’s a privilege to work alongside them
Dramatic results from
@wendy_bickmore
& co on Shh gene regulation in the limb
Are TADs necessary? Nope
Are CTCF binding sites necessary? Nope
Is physical proximity of enhancer-promoter important? Nope
Do we understand long-range gene regulation? Nope
I’m delighted and honoured (and a little trepidatious) to be appointed the next Editor-in-Chief of
@Dev_journal
I take over in September & excited by the challenge. I’m making plans. I’d love to hear your thoughts, ideas, hopes and fears for the journal.
Job Alert!
@TheCrick
is recruiting early career group leaders (again)
All areas of bio, biomed & related research
12 years core funding, great facilities, fantastic colleagues (& me)
Deadline: 6 October
Details:
Surprised, delighted, and overawed to be elected an International member of the American Academy of Arts & Sciences
@americanacad
A huge honour, made even more so by the inspiring accomplishments of the other new members
Congratulations to our new members! Just announced! We are honoring the excellence of extraordinary leaders in an array of disciplines and professions. The first members were elected in 1781. Learn who was elected in 2023:
Our latest: a new optogenetic system for precise spatiotemporal control of gene expression
We use it to dissect the dynamics of Shh gradient formation & patterning
A thread 🧵
It's a shame
#CRISPRBabies
dominated the news this week as the development of placenta organoids likely to be of much more long term significance for Dev Bio and reproductive medicine
I'm working my way through this year's applicants for
@TheCrick
faculty positions
Lots of strong and exciting candidates. However I'm surprised by how many publication lists have "submitted"/"in revision" to some fancy journal but no preprint available
#showmethescience
Just realised it’s 20 years since I started my lab in the attic of MRC-NIMR
No idea where the time went. I’m still trying to figure out what I’m meant to be doing
Very grateful to friends, collegues, lab members past & present from
@GhostofNIMR
&
@TheCrick
for their support
New from the lab:
@robertblassberg
& co on how the levels of SOX2 influence where WNT signaling effectors bind to chromatin
This determines the WNT response & explains how one signal elicits different responses in different cell types
#OA
Sorry to learn of Sydney Brenner's death
Without diminishing his scientific & institutional contributions, I have fond memories of his
@CurrentBiology
column "Loose Ends"
As a student it gave me a humorous & honest insight into reality of research
I’m delighted and honoured to be taking over as Editor-in-Chief of
@Dev_journal
Here’s my first editorial
There’s never been a more exciting time to be a developmental biologist and
@Dev_journal
is here to support and champion the latest and greatest
Our latest: We explore how cells interpret morphogen gradients during development using optimal control theory
A thread explaining some of the ideas 🧵
1/12
Our latest: Quantifying Waddington Landscapes
* Constructed dynamical models of ES cell differentiation from data
* Identified 2 fundamentally distinct mechanisms of binary decisions
* Models make quantitative predictions & generally applicable
The burning questions in gene regulation:
Does liquid-liquid phase separation enable gene regulation?
Is chromatin topology important for gene expression?
Mustafa Mir & co provide answers in:
Surprising news:
@sangerinstitute
is closing its animal research facility
Because “using alternative technologies to deliver its scientific strategy”
I’m prepared to bet in ~5 years time, the next strategic review will propose to open an animal facility
Our latest: Notochord and axial progenitor generation by timely BMP and NODAL inhibition during vertebrate trunk formation
Combining transcriptome analysis of vertebrate embryos & 2D+3D ES cell differentiation to study trunk formation & notochord generation
Thread...
1/n
Our latest: What controls the pace of development?
Human motor neurons differentiate 2.5X slower than mouse
Not due to differences in signalling or regulatory elements
Human proteome 2X more stable than mouse & explains tempo difference
We're recruiting a PhD student
Interested in developmental & stem cell biology?
Want to live in London?
Like to be part of
@TheCrick
fantastic graduate student programme?
Applications are open. Deadline Nov 11
Enjoying reading today's single cell papers
I've done the calculation & extrapolating from recent publications I can confidently predict a paper will be published in 2020 in which more cells than atoms in the universe are sequenced at a depth of less than 1 transcript per cell
As 2020 peters out, one thing I never thought I’d be grateful for, as a scientist, is 26 consecutive weeks of negative results
Thanks
@TheCrick
#COVID19
testing for helping keep research going
How do precise boundaries of gene expression form in developing tissues?
Although differential adhesion & mechanics receive lots of attention, we find dynamics of gene regulatory network suppress effect of noise & contribute to precision
After 8 months & 80000+ jabs the vaccination centre
@TheCrick
is closing
Proud to have played a part with ~50 shifts & ~2000 jabs
I'll remember many happy patients, the professionalism of the
@uclh
staff, & some questionable choices of arm tattoo
Our latest review of neural tube development
Morphogen gradients, gene regulatory networks, spatial & temporal control of gene expression
New observations & experimental approaches offer insight into origin of neuronal diversity
The importance of theory and ideas (as well as data) for biology. By my
@TheCrick
colleague Paul Nurse
"Ideas, even tentative ones, are needed, along with the recognition that ideas will change as facts and arguments accumulate.”
Our latest: Deep dynamical modelling of developmental trajectories with temporal transcriptomics
Experimental & computational methods for robust dynamical modelling of gene expression from single-cell transcriptomic data
A thread 🧵
Our latest: an integrated experimental & computational framework for dynamical modelling of gene expression with time-resolved single-cell transcriptomics using metabolic labelling of RNA
by
@rorymaizels
et al
🧵
Developmental biology is fundamental to the human experience argues John Wallingford
Fantastic piece championing the field
And interesting fact:
"congenital disorders are twice as lethal as cancer for young people in the United States”
This is tragic news
Suzanne Eaton was a pioneer, scientific star & superb mentor
It's a devastating loss to the developmental and cell biology
My thoughts are with her family, friends & colleagues
This should give all of us serving on grant panels pause for thought:
“the peer review system is not substantially better than random selection in identifying the best candidates once an initial pre-selection of the most promising ones is performed”
Our latest: Quantifying Waddington’s landscape
Theory & xpts to construct dynamical models of differentiation:
- makes testable quantitative predictions
- reveals two fundamental cell decision mechanisms
- generally applicable to wide range of systems
Our latest: How does one signal produce different responses in different cell types?
WNT signaling maintains ES cells, posteriors epiblast, induces mesoderm
SOX2 levels determines WNT response by recruiting TCF/b-catenin to different genomic targets
Our latest: A shared transcriptional code orchestrates temporal patterning of the central nervous system
We define TFs expressed sequentially in neurons & progenitors that act in parallel to spatial patterning to diversify neurons throughout the CNS
1/n
Our latest: single cell RNAseq of ~20000 cells from developing neural tube
Main findings:
• identifies known & new cell types
• coordinated temporal programme complements spatial patterning
• reveals dynamics of gene expression during neurogenesis
Our latest: Developmental cell fate choice employs two distinct cis regulatory strategies
Two ways CREs interpret morphogens
1. Differential binding: CREs bind cell type specific inputs
2. Differential access: availability of CREs is cell type specific
Don’t miss the collection of articles in
@Dev_journal
commemorating the work of Suzanne Eaton
@eaton_lab
Highlights her contributions to understanding planar cell polarity, hedgehog signaling, tissue mechanics & the developmental role of lipids
How does DNA methylation regulate gene expression?
Howard Cedar & co hypothesise that it's about methylation of (non promoter) enhancers & silencers
Pioneer factors mediate cell-specific demethylation & open regulatory elements by recruiting TET etc
Our latest: Temporal patterning of the CNS by a shared transcription factor code
Sets of TFs expressed sequentially in neurons & progenitors act in parallel to spatial patterning to diversify neuronal subtype identity throughout the CNS
News from
@Dev_journal
We’ll be publishing (anonymous) peer review reports - as soon as we can sort out logistics
We’re signatories of the
@ASAPbio_
letter encouraging others to follow
See commentary from
@jessicapolka
and co
Big job alert! Probably the biggest job in UK science: CEO of
@wellcometrust
replacing
@JeremyFarrar
next year
Hopefully they'll find someone to champion discovery science & increase investment in the curiosity driven research that underpins innovation
Beautiful work by my
@TheCrick
colleagues in the
@jpvincentlab
A synthetic morphogen gradient made by secreted GFP can substitute for Dpp in the wing disc
No cytonemes, argosomes, multiprotein particles, just diffusion & receptor binding
In case anyone asks if now is the best time ever to be a developmental biologist. Two papers out today:
Insight into an ancient axis elongation gene regulatory network.
Generation of human organiser initiating axis formation
Congratulations and good luck to
@metzisv
Leaving
@TheCrick
to start her own group
@MRC_LMS
Drop her line if you're looking for a great post-doc/studentship/tech position in 2020
Our latest: Cis-regulatory strategies for morphogen dependent cell fate decisions
Two ways CREs interpret morphogens
1. Differential binding: CREs bind cell type TFs
2. Differential access: availability of CREs is cell type specific
ICYMI:
@MarinLab
& I wrote a perspective for
@ScienceMagazine
"Looking at neurodevelopment through a big data lens"
Started over coffee conversation about new technology in genomics, genetics & organoids changing our understanding of neurodevelopment
Human embryo research beyond the primitive streak
We argue it’s time to revisit the 14 day limit for in vitro culture & a science led progressive extension of culture period, coupled with public dialogue is the right way forward
Really excited to launch
@Dev_journal
"Pathway to Independence Programme"
Are you, or do you know, a dev bio or stem cell researcher planning to apply for their 1st PI position in 2023?
Then this scheme is for you. See how to apply:
This may have escaped notice in other news today:
@EMBO
have extended all active (as of 16 March 2020) EMBO Long-Term Fellowships for two months to compensate for any impact from closures or other safety measures taken in the labs they are working at.
Concerning news that
@The_MRC
is planning to close the Mammalian Genetics Unit of
@MRCHarwell
Doubly concerning as
@sangerinstitute
closes its mouse facilities
The UK urgently needs a coordinated strategy for mouse genetics and model research
Today at
@KITP_UCSB
#morpho19
we're celebrating Suzanne Eaton's contributions to the fields of cell and developmental biology
Here Frank Julicher describes his long running & successful collaboration with Suzanne, involving weekly joint lab meetings
cc
@eaton_lab
Extremely frustrating listening to gov ministers dissembling on testing capacity when universities & institutes have offered 1000s of skilled volunteers willing to help & the equipment (including for protein purification) to make & perform tests. Communication or policy failure?
Mistake or not (of course it’s complex), it clearly has been a policy decision. As you say, huge capacity for RT-PCR across the country - reagents, personnel and machines.
New paper: how to construct quantitative dynamical models of cell fate decisions
Combining catastrophe theory & experimental data
Provides a classification of decision types & relates dynamical systems to Waddington landscapes, competence, commitment
TAD-Da or TAD-Nah
Shuffling or fusing TADs or disrupting inter-TAD loops has no effect on most gene expression
Something other than chromatin topology determines enhancer–promoter specificity
Provocative results from
@Eileen_Furlong
& co
Are you a developmental or cell biologist?
Looking for an alternative social media platform?
Wouldn't it be good if it was especially for biologists to discuss science, research, teaching...?
Yes? Try
@Co_Biologists
Mastodon server
@biologists
.social
Completely agree with Ben MacArthur
"theory is not a dispensable add on to ... experimental science but ... a central part"
Helpful summary of what makes a good theory with examples
Our latest preprint. How gene regulatory networks make sharp boundaries
Main findings:
* Structure of GRN contributes to precision in neural tube
* GRN suppresses effect of gene expression noise
* GRN designs that produce precise gene expression patterns
“Assembloids” in
@sciencemagazine
OK, I’m calling it: we’ve hit peak “oid” - it’s only down hill from here
I’m eagerly anticipating launch of new journal Celluloid…
Back in the lab after >10 weeks. Still far from normal and won't be so for a while. But cells growing and can finally start those "last little" experiments to finish a couple of papers...
Great to see
@geochurch
becoming a developmental biologist (it's never too late)
Systematic identification of txn factor receipes for cell fate reprogramming
Paul Nurse: “We are facing an utterly chaotic situation, a failure of statecraft and political leadership, which has led to this almost wartime footing, driven by an ideology that simply doesn’t understand the modern world.”
🎙️ Our director Paul Nurse spoke to
@BBCr4today
this morning and spelled out the risks that a no-deal Brexit poses for science.
Listen to the full interview here from 2:50:00 ➡️
🇪🇺🇬🇧 |
#DealForScience
Just a reminder if you haven't had your 1st
#vaccine
yet, or it's time for your 2nd, we're still here and waiting for you
Book your appointment
@TheCrick
(or just turn up to a walk in centre)
So today I read TADs are really important for gene regulation:
And I also read that TADs are really unimportant for gene regulation:
<sigh> <shakes-head> <gives-up>
I’m attending
#DevDMM21
Developmental Disorders meeting this week
Despite all the "my embryo is better than yours” chat on my timeline, it reminds me that all models can be useful
And at
@Dev_journal
we don’t do favourites, we equally love all embryos (& organoids too)
I’m delighted to be elected a fellow of the Academy of Medical Sciences
Also great that it's alongside colleague & fellow developmental biologist
@devsiglab
- strong signal that the Academy continues to value fundamental research in medical science
"Is there a recent review of the
#morphogen
control of tissue patterning that I can read on my summer hols?" I hear you ask
Why, yes, there is. Here's
@AKicheva
& my summary of the current state of the field & open questions
Very pleased about the launch two new features in
@Dev_journal
1. Peer review history - referee reports, author responses, editor letters - will be published alongside papers
2. Publons partnership - allows reviewers to track refereeing contributions
An interview with Jean-Paul Vincent
JP
@jpvincentlab
@TheCrick
was awarded the 2024
@_BSDB_
Waddington Medal, which honours outstanding research performance and services to the developmental biology community. Read the interview:
Our latest: Revisiting CNS regionalisation. Wnt signaling commits cells to spinal cord fate before neural induction
Reverses order proposed in classic ‘Activation-Transformation’ model
Led by
@metzisv
&
@ssteinhauser2
great collaboration w/
@luscombelab
I was deeply saddened to hear that Tom Jessell died yesterday (April 29)
For me & many others he was an inspirational mentor and he leaves a towering scientific legacy
My thoughts are with his family
Are you a developmental or stem cell biologist looking for an academic job? Would you like support & advice
This year's
@Dev_journal
'Pathway to Independence' programme is open for applications
Deadline 31 Jan 2024
Spread the word
Details:
Commentary summarising current state of the
#DevBio
field with concrete proposals & a call to action
- Increase organismal diversity
- Improve funding (& support reviewing)
- Encourage new entrants to the field
- Support data sharing & public outreach
Just accepted the first paper for
@Dev_journal
from
@ReviewCommons
- it’ll be online soon
My perspective as an editor: reviews were science focused & helpful; authors’ responses constructive; the whole process rapid & efficient
The future of peer review?
Sad to hear Lewis Wolpert has died
An intellectual giant of developmental biology, committed contrainain but great supporter of many in the field
I have fond memories of several extended lunches in UCL’s Housman Room while Lewis held court & entertained
I am very sad to hear that the great developmental biologist Lewis Wolpert died this morning at the age of 91. He was a giant in my field, and will be missed.
The 2024 PhD programme
@TheCrick
is recruiting
Includes a project in my lab
• Innovative science
• International, collaborative environment
• Structured programme, training & career support
• £26,125 tax-free + tuition & visa fees
Apply by 9 Nov
Our human embryo spinal cord single cell
#scRNAseq
data now available through
#CZCELLxGENE
portal
For full description of the dataset see the original
@Dev_journal
paper
Useful reminder from
@LickertHeiko
& co that there is no such thing as
#mesendoderm
Meso- & endoderm are separate lineages in primitive streak
Mesoderm undergoes conventional EMT, but endoderm forms independent of Snail1 via epithelial cell plasticity
Touching obituary for Suzanne Eaton by Frank Julicher, one of her closest collaborators
"Working with her was always a joyful experience, playful and deeply enlightening"
Scholarly, insightful & a pleasure to read
The primitive streak & gastrulation
The authors argue conserved signals & GRNs characterise gastrulation but lead to variation in morphological appearance due to species differences in boundary conditions
Lots of excitement about
@DeepMind
#alphafold2
Props to
@embl
for making it available to everyone - it’s easy to forget the importance (but less glamorous business) of making data & services accessible & easy to use
Very pleased to see first
@Dev_journal
paper published with its peer review history
Shows referees’ reports, authors’ responses, editor’s letter, timeline
Offers more transparency to the publishing process & context to published papers
I hope more authors agree to participate
We've just published our first 'peer review history' file - includes a timeline, referee reports & author responses. Delighted to be opening up the editorial process to our readers.
Good news that UK passed 10M COVID-19 vaccines & pleased
@TheCrick
has played a small part
I hear Peter Ratcliffe is doing shifts alongside other staff & students, raises the question is it the only place you can get the jab from a
@NobelPrize
winner?
I like this definition of mechanism from
@yoginho
" [mechanism] not only requires the decomposition of a system through genetic and molecular methods, but also its reconstitution in terms of dynamic mathematical models"
Thomas M. Jessell (1951-2019)
Silvia Arber and I remember Tom Jessell, who died last month
Tom revolutionized our understanding of neural tube development and circuit formation. We highlight some of his most important scientific contributions
Our latest: Developing an optimal control approach for analysing tissue patterning
Morphogen signalling as a control strategy to guide patterning while minimising signalling & time
Offers insight into how patterning is timely, precise & reproducible
Are you a
#DevBio
or
#StemCell
post-doc going on the academic job market this year?
Take a look at
@Dev_journal
Pathway to Independence programme
Mentorship & networking to support the transition from post-doc to PI
Application deadline Jan 31
We at
@Dev_journal
allow format-free submission
At first submission, submit your manuscript in any format
And if you’re worried about scope, send us a presub enquiry and we should be able to answer you in a few days (even at Thanksgiving)
"the agreement enables the UK's continued participation in a number of flagship EU programmes for the period 2021-2027 (subject to a financial contribution by the UK to the EU budget), such as Horizon Europe"
Delighted our latest paper "Single cell transcriptome map of the developing mouse neural tube” is in
@devjournal
#singlecell
special issue
Summary follows: