EMBL Seminars

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Abstract
With their Janus-faced property of being at once dynamic and stable, epigenetic mechanisms have for long been proposed to act as molecular mnemonics, and multiple studies have revealed that learning induces an altered epigenetic make-up in neuronal cells. However, whether inversely, an altered epigenetic make-up can lead to altered memory performance has so far remained unresolved. My recent research has contributed to answering this question two-fold. 

First, we identified chromatin plasticity as a novel form of plasticity important for information encoding. We found that the epigenetic makeup of developmentally identical neurons in the adult mouse brain is characterized by intrinsic heterogeneity, which, when experimentally altered, dictates which neurons become recruited into the ensemble of cells storing the memory. Second, we provided a proof-of-principle that site-specific epigenetic dynamics are causally implicated in memory expression. Focusing on the promoter region of Arc, a master regulator of synaptic plasticity, we found that its locus-specific and temporally controllable epigenetic editing is necessary and sufficient to regulate memory expression. 

These studies indicate that the brain may capitalize on epigenetic mechanisms to store behaviorally acquired memories by means of co-opting processes otherwise used for defining cellular memories.

Abstract

Moving cells navigate inside living tissues often encountering obstacles and junctions, where their path branches into alternative directions of migration. This is the case of cells moving on top or within blood vessels, which often bifurcate into branches. Cells have diverse migratory strategies that differentially rely on the adhesion to the substrate. Cells that undergo mesenchymal migration are highly dependent on the adhesion to the substrate, and when facing bifurcations are forced to coordinate the adhesion and detachment of the competing branches. Recent studies showed how the decision is made -to keep or retract a branch and choose a new direction- when there is bias: open versus dead-end, differences in pressure, presence/absence of a chemoattractant. However, much less is know about how cells decide a new direction when the decision is unbiased. Similarly, it is poorly understood how migrating cells coordinate membrane dynamics during branching to maintain a good trade-off between microenvironmental exploration and migratory efficiency.  Here, we use in vitro live-cell imaging using different levels of complexity, and advanced image analysis to analyze the response of migrating cells when facing symmetric junctions, and extreme branching when cells simultaneously face several bifurcations. We found that actin and membrane dynamics play a key role to choose a new direction path in both cases i) when cells face a single junction (Ron et al. 2024), and ii) when cells exhibit high levels of branching because they face several junctions at the same time (Liu et al.). In addition, we found that migrating immune cells have a fine tune regulation of branching in order to coordinate surveillance and migration. These results shed light on the mechanisms by which cells resolve unbiased junctions and branching during cell migration. 

Abstract
I will discuss how vertebrate skin colours and skin appendages (scales, feathers, hairs, …) are spatially patterned through Turing and mechanical instabilities. First, I will show that Reaction-diffusion (RD) models are particularly effective for understanding skin colour patterning at the macroscopic scale, without the need to parametrise the profusion of variables at the microscopic scales. I suggest that the efficiency of RD is due to its intrinsic ability to exploit continuous colour states and the relations among growth, skin-scale geometries, and the (Turing) pattern intrinsic length scale. Second, I will show how drug treatments can permanently trigger transitions between scale appendage types or even between chemical and mechanical self-organisation. Third, I will show that a three-dimensional mechanical model, integrating growth and material properties of embryonic skin layers, captures most of the dynamics and steady-state pattern of head scales in crocodiles. Finally, I will show how these two processes (mechanical and RD) can co-exist in some lineages such as tortoises. These studies indicate that Biology, despite its ‘messy’ nature (with its unmanageable profusion of cellular & molecular variables) can be efficiently and quantitatively investigated mathematically, including with simple phenomenological models. 

Join us at the next Project Management Network event to discover how AI is reshaping project management.

Generative AI is reshaping the way programme and project managers work. From automating documentation to building project plans and identifying risks—AI is becoming a powerful ally in smarter, more strategic project management.

Speaker:

Prof. Dr. rer. nat. Daniel Mertens (Research Group Leader, German Cancer Research Centre (DKFZ) & University Hospital Ulm). Since 2023, Prof. Mertens has led more than 170 AI-focused workshops, training over 8,000 participants to integrate AI into daily work. He has also trained more than 9,000 scientists and professionals in transferable skills, while coordinating major international research networks.

What you’ll learn:

·       Generative AI for project management
·       Smarter project planning & scheduling with AI
·       Identifying, evaluating and responding to project risks using AI

This session will be perfect for anyone looking to strengthen their project management skills with the power of AI.

If you have any questions, please contact Anna Rupaningal (alr@ebi.ac.uk) or Simone Vegh (vegh@ebi.ac.uk).

All are welcome! We look forward to seeing you at the session.

Anna & Simone
 

Abstract
Olfactory sensory neurons express in a seemingly stochastic, monogenic, and monoallelic fashion one out of more than a thousand genes. This singular choice is accomplished by overlapping epigenetic mechanisms that gradually reduce the complexity of olfactory receptor expression to a few co-transcribed alleles that compete for transcriptional dominance. I will describe how the assembly of interchromosomal, multi-enhancer hubs enables oligogenic olfactory receptor expression in immature olfactory neurons, and how and RNA-mediated symmetry breaking process assures that only one of the co-transcribed alleles will remain transcriptionally active in mature olfactory neurons. 

Abstract
The mechanisms underlying specific enhancer-promoter (E-P) pairing remain largely unclear. While chromosome extrusion by cohesin has been proposed to facilitate E-P proximity, cohesin loss affects only a small subset of genes, suggesting additional factors mediate spatial regulatory connections. Beyond the generic CTCF/cohesin machinery, few nuclear factors have been examined through acute perturbation to determine their direct role in physically linking regulatory elements. Through acute degradation experiments, we discovered that the transcription co-factor LDB1 spatially connects a substantial fraction of E-P loops. LDB1 exerts this function in cooperation with single-stranded DNA binding proteins (SSBPs). Leveraging the dynamic re-establishment of nuclear architecture during the transition from mitosis to G1-phase, we established a relationship between LDB1-dependent chromatin occupancy and loop formation. Region-Capture-Micro-C (RCMC) and Tri-C experiments revealed that LDB1 organizes multi-enhancer networks to activate transcription. Using multiple degron systems, I will outlined the varied yet limited influence of CTCF, cohesin, and the chromosome loop extrusion factor NIPBL on LDB1-dependent regulatory connectivity.

The adapter molecule LMO2, which links LDB1 to transcription factors at specific genomic loci, is frequently overexpressed in T-Cell Acute Lymphoblastic Leukemia (T-ALL). I will present recent studies LDB1's role in spatially connecting enhancers to oncogenes in T-ALL.

In sum, I look forward to discussing how the LDB1 complex spatially organizes the mammalian genome in normal and cancerous cells.

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Abstract
The presentation will outline recent advances in disease prediction through the integration of national health registries, genomic data, and artificial intelligence. Using data from the Finnish FinRegistry (over 7 million individuals and 6.5 billion records), large-scale machine learning models achieve high predictive accuracy for disease outcomes but also reveal disparities across regions and socioeconomic groups, emphasizing fairness and generalizability challenges. The presentation will further demonstrate how polygenic scores (PGS) capture lifelong disease risk and complement electronic health record–derived phenotype risk scores (PheRS), with each excelling for different disease categories. Combining genomic and EHR data enhances trial emulation, strengthens causal inference, and supports the design of more representative clinical studies. The talk will underscore that equitable, ethically guided AI and genetic integration are key to realizing precision prevention at a population scale.

Abstract
[Text for abstract].

About the speaker
[Biographical information about the speaker].

Meet the speaker
To meet with the speaker informally after the talks,sign up here [add link]. We especially encourage predocs and postdocs to take advantage of this opportunity.

Attachments
[Link to a file (for example a pdf of the seminar’s programme) - the file can be uploaded on the intranet]

Connection details
Zoom*: [https://embl-org.zoom.us/j/96374261689?pwd=TnNxRWtQY2lyc2pSa2JpY3NGcDlhZz09] (Meeting ID: [963 7426 1689], Password: [DBU])

Please note that the talk will yes/not be recorded.
*For the FAQ section, as a zoom participant, please use either the chat function (the host will read out your question) or the “raise your hand” function and turn on your microphone.

Abstract

Epigenetic components regulate many biological phenomena during development and normal physiology. When dysregulated, epigenetic components can also accompany or drive diseases. One main class of epigenetic components are Polycomb group proteins. Originally, Polycomb proteins were shown to silence gene expression. We found that this function involves the regulation of 3D chromosome folding and we found that Polycomb components can induce the formation of long-distance interactions or chromatin loops that may play instructive roles in gene regulation as well as serve as scaffolding elements that contribute to enhancer-promoter specificity. Perturbation of Polycomb components is involved in human cancer and leads to tumorigenesis in flies. Surprisingly, even upon a transient depletion followed by restoration of the full Polycomb compendium, epithelial cells lose their normal differentiated fate, continue proliferating and establish aggressive tumors, demonstrating that cancer can have a fully epigenetic origin. Similarly, transient perturbation of histone acetylation in mouse ES cells and gastruloids shows that they can record chromatin changes and that this results in cellular memory of the perturbation states. The implication of these data will be discussed.