Billions going unspent from Australia’s $24b medical research fund Costings commissioned by independent MP Monique Ryan reveal the government could double how much funding it gives to innovative health research each year.

www.theage.com.au/politics/fed...

18/ At large genomic distance, long encounters (=the important ones) are only due to loop extrusion; but at short genomic distance they can also be due to random collisions. This is why enhancers are no sensitive to loss of extrusion when they are close, but sensitive when they are far!

Really excited to share our latest work led by @mattiaubertini.bsky.social and @nesslfy.bsky.social: we report that cohesin loop extrusion creates rare but long-lived encounters between genomic sequences which underlie efficient enhancer-promoter communication.
www.biorxiv.org/content/10.1...
A🧵👇

We are looking for a student to continue our work on chromatin evolution:
www.nature.com/articles/s41...
www.biorxiv.org/content/10.1...

The project with @seanamontgomery.bsky.social will focus on chromatin state readers across eukaryotes.

More info: recruitment.crg.eu/content/jobs...

New preprint from the lab 🎉 on the evolution of gene regulatory network complexity, where we tested whether sexual recombination promotes more complex GRNs using biochemically-inspired evolutionary simulations 🧐. Bluetorial from 1st author @chapelmadison.bsky.social 👇

Regulation of somatic hypermutation by higher-order chromatin structure Schoeberl et al. employ Tri-C to unravel the higher-order chromatin architecture underpinning the co-transcriptional mutagenesis of immunoglobulin genes during antibody maturation in human B cells. They provide evidence that antibody maturation occurs within a dynamic multiway hub wherein transcription and mutation of different genes occur non-competitively.

Online Now: Regulation of somatic hypermutation by higher-order chromatin structure Online now:

A cellular entity retaining only its replicative core: Hidden archaeal lineage with an ultra-reduced genome Defining the minimal genetic requirements for cellular life remains a fundamental question in biology. Genomic exploration continually reveals novel microbial lineages, often exhibiting extreme genome...

So cool, a novel archaeon with a super small genome and no metabolic genes!
"An unprecedented level of metabolic dependence on a host, a condition that challenges the functional distinctions between minimal cellular life and viruses."
www.biorxiv.org/content/10.1...

Many cells during development are exposed to caspase activation and yet survive. Why some die and not others ? We found out that the memory of previous caspase activation bias significantly later death comitment and bias death distribution and single cell decision
www.biorxiv.org/content/10.1...

Clonal tracing with somatic epimutations reveals dynamics of blood ageing - Nature The discovery that DNA methylation of different CpG sites can serve as digital barcodes of clonal identity led to the development of EPI-Clone, an algorithm that enables single-cell lineage tracing th...

Out @nature.com: Clonal tracing with somatic epimutations

🧬 Single cell methylome encodes cell state & clonal identity

🔨 EPI-Clone reads out both (+mutations, +RNA) at scale

🩸 Clonal expansions of HSCs are universal from age 50, not driven by CH mutations

doi.org/10.1038/s415...
🧵

Design principles of cell-state-specific enhancers in hematopoiesis Screen of minimalistic enhancers in blood progenitor cells demonstrates widespread dual activator-repressor function of transcription factors (TFs) and enables the model-guided design of cell-state-sp...

Out in Cell @cp-cell.bsky.social: Design principles of cell-state-specific enhancers in hematopoiesis
🧬🩸 screen of fully synthetic enhancers in blood progenitors
🤖 AI that creates new cell state specific enhancers
🔍 negative synergies between TFs lead to specificity!
www.cell.com/cell/fulltex...
🧵

🐛🕷️🕸️ @science.org Hawaiian caterpillar patrols spiderwebs camouflaged in insect prey’s body parts | Science www.science.org/doi/10.1126/... #entomology

DNA-guided transcription factor interactions extend human gene regulatory code - Nature A large-scale analysis of DNA-bound transcription factors (TFs) shows how the presence of DNA markedly affects the landscape of TF interactions, and identifies composite motifs that are recognized by complexes of TFs rather than by individual ones.

Nature research paper: DNA-guided transcription factor interactions extend human gene regulatory code

https://go.nature.com/4j13XRc

DNA-guided transcription factor interactions extend human gene regulatory code - Nature A large-scale analysis of DNA-bound transcription factors (TFs) shows how the presence of DNA markedly affects the landscape of TF interactions, and identifies composite motifs that are recognized by ...

www.nature.com/articles/s41...

our work on the molecular differences between transcription factor isoforms is out now in Molecular Cell!

key point: 2/3rds of TF isos differ in properties like DNA binding & transcriptional activity

many are "negative regulators" & misexpressed in cancer

www.sciencedirect.com/science/arti...

1/ H3K27me3 mimicry has repeatedly emerged through evolution, but what's the physiological relevance?

We show that JARID2 and PALI1 mimic H3K27me3 to antagonise PRC2 in vivo and restrict the spread of Polycomb domains.
🧵
www.biorxiv.org/content/10.1...

Disabling leading and lagging strand histone transmission results in parental histones loss and reduced cell plasticity and viability Losing parental histones during DNA replication fork passage challenges differentiation competence and cell viability.

𝐇𝐨𝐰 𝐝𝐨 𝐜𝐞𝐥𝐥𝐬 𝐫𝐞𝐦𝐞𝐦𝐛𝐞𝐫 𝐰𝐡𝐨 𝐭𝐡𝐞𝐲 𝐚𝐫𝐞 𝐚𝐟𝐭𝐞𝐫 𝐃𝐍𝐀 𝐫𝐞𝐩𝐥𝐢𝐜𝐚𝐭𝐢𝐨𝐧? Our new study “Disabling leading and lagging strand histone transmission results in parental histones loss and reduced cell plasticity and viability” is out in 𝘚𝘤𝘪𝘦𝘯𝘤𝘦 𝘈𝘥𝘷𝘢𝘯𝘤𝘦𝘴. Led by @lleonie.bsky.social @biranalva.bsky.social 🧵 More below👇

We need a genbank database

Yeah I don’t really care how they made the plasmids. Just give me the genbank file.

Asteroid fragments upend theory of how life on Earth bloomed Samples from Bennu contain the chemical building blocks of life - but with a twist.

Not only does Bennu contain all 5 of the nucleobases that form DNA and RNA on Earth and 14 of the 20 amino acids found in known proteins, the asteroid’s amino acids hold a surprise

https://go.nature.com/4hDtGhL

We hope that people find these ideas interesting, and that they maybe even provide new hypotheses to test experimentally. Thanks to Omer Gilan and @faulknerlab.bsky.social for help exploring these ideas over the last 5-6 years.

One of the main goals of this review was to help clarify some of the confusion in the field about "epigenetics", specifically the interplay between TFs and histone mods. Here, we attempt to unify the role of transcription factors and histone modifications under a single conceptual framework.

Chromatin memory has been appreciated for a long time, but we believe its implications have not been fully explored. The capacity for local, chromatin memory to stabilise non-encoded cell states has major implications for the evolution of cell types and formation of resistant cell states in cancer.

Chromatin-based memory as a self-stabilizing influence on cell identity - Genome Biology Cell types are traditionally thought to be specified and stabilized by gene regulatory networks. Here, we explore how chromatin memory contributes to the specification and stabilization of cell states...

"Everything in epigenetics is circular". Here, we explore how memory that is stored locally on chromatin has a crucial role in stabilising cellular state, updating our view of the epigenetic landscape from one shaped by the genotype, to one moulded by experience

doi.org/10.1186/s130...

Collage of the 24 Development cover images in 2024

📢Vote for the 2024 Development cover image of the year

@dev-journal.bsky.social featured 24 cover images in 2024. Now is the chance to pick your favourite!

Browse through the images and vote by 13 Jan:
https://thenode.biologists.com/vote-for-the-2024-development-cover-image-of-the-year/

#DevBio

Timely TGFβ signalling inhibition induces notochord - Nature Through analysis of developing chick embryos and in vitro differentiation of embryonic stem cells, a study develops a method to generate a model of the human trunk with a notochord.

Our latest: how to generate the notochord
"Timely TGFβ signalling inhibition induces notochord"

A thread:

www.nature.com/articles/s41...

Building a backbone: scientists recreate the body’s ‘GPS system’ in the lab Scientists at the Francis Crick Institute have generated human stem cell models1 which, for the first time, contain notochord – a tissue in the developing embryo that acts like a navigation system, di...

Crick researchers have recreated a tissue in the lab that acts like a developing embryo’s navigation system, directing cells where to build the spine and nervous system.

The findings were led by Tiago Rito with senior author @jamesbriscoe@bsky.social

www.crick.ac.uk/news/2024-12...

Dynamics of positional information in the vertebrate neural tube | Journal of The Royal Society Interface In developing embryos, cells acquire distinct identities depending on their position in a tissue. Secreted signalling molecules, known as morphogens, act as long-range cues to provide the spatial info...

New in J R Soc Interface: How temporal dynamics of morphogen signalling increases positional precision in vertebrate neural tube development

Combining Shh & BMP signals over time provides significantly more spatial information than static gradients alone

doi.org/10.1098/rsif... #DevBio

Optimized reporters for multiplexed detection of transcription factor activity Direct measurements of transcription factor (TF) activity are crucial for understanding how TFs interpret signals and drive gene expression. TF reporter constructs have been widely used to detect activity in cell signaling, developmental biology, and disease models. However, many mammalian TFs lack reliable reporters. In this study, a library of reporters for 86 TFs was designed and evaluated to identify optimized “prime” TF reporters.

Excited to share that my main PhD project has been published! 🎉 We systematically designed and optimized reporters for 86 transcription factors in parallel. If you're interested in using these optimized reporters for your own research, don’t hesitate to reach out!

What is the origin of universality in complex systems? This 1979 paper by Ken Wilson in @sciam.bsky.social
explains the Renormalization Group, one of the most powerful ideas in physics. Used to study everything from magnets and liquids to ecosystems and societies.
jstor.org/stable/24965...