EMBL Seminars

Abstract
African Trypanosomes proliferate within the bloodstream and tissue spaces of mammals and can maintain a long-term infection often lasting for years. To do this, trypanosomes must avoid the host adaptive and innate immune response at the same time as acquiring nutrients from the host. There is a good understanding of how the adaptive immune response is distracted through a population survival strategy based on antigenic variation a densely packed surface coat made of a variant surface glycoprotein (VSG). There is also a strong selection pressure to prolong the survival of individual trypanosomes presumably to increase the chances of returning to a tsetse fly, the definitive host. There is rapid clearance of antibodies bound to the cell surface and a set of conserved receptors that decrease the effectiveness of complement pathways. A second set of receptors is involved in the acquisition of host macromolecular nutrients. 

Why do these conserved receptors not lead to immune clearance?  Work on how the receptors bind ligands, how trypanosomes have evolved to have a wide host range, and what happens when on ligand binding have been integrated to form a model of how they are able to form life-long infections. 

Connection details
Zoom*: https://embl-org.zoom.us/j/99010203982?pwd=eKlBm1821yrpjddaCbanN6CjooJL8y.1 

(Meeting ID: 990 1020 3982, Password: 717935)

Please note that the talk will 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
Advances in AI now make it possible to mine unprecedentedly large and multimodal biomedical datasets for mechanisms that could transform scientific discovery, diagnostics and therapy. Yet, without formal guarantees of identifiability, these models risk producing representations and predictions that are scientifically ungrounded and clinically unreliable. Identifiability refers to the statistical property of being able to infer structure from data relating to the actual causal or generative processes rather than arbitrary representations. In this talk, I first present recent advances in representation learning for uncovering mechanisms directly from neural time-series data. I then turn to foundation models, presenting new methods for interpretability that map their learned representations to semantic concepts understandable to human experts. Such a tight integration of theoretically grounded AI for mechanism discovery paired with semantic interpretability offers a path toward AI systems that are both scientifically valid and clinically reliable.

Abstract
Group leaders based in Germany, Austria, and the US, will share their experience of negotiating their group leader role. Following the speakers' introductory presentations, participants will have the opportunity to ask questions during a panel discussion. Join to gain insights into the negotiation process and how to prepare to make the most of your first group leader position!

Please register for this zoom webinar: https://embl-org.zoom.us/webinar/register/WN_NNV9KmXCRFSGCfRgqJSxEQ#/registration

Please note that the talk will be recorded.
*For the FAQ section, as a zoom participant, please use either the chat function (the host will read out your question).

Abstract
Bridging the concentration gap between the dispersed state of intrinsically disordered biopolymers and their high-concentration states relevant for cellular environment, including membrane-less organelles, as well as for food biochemistry and food technology, is a serious challenge. In this talk, I will present an approach based on the conventional and newly developed pulse EPR techniques and aimed to describe the spatial and conformational distributions in biomolecular condensates and weak aggregates. This methodology can potentially also shed light on the biomolecules’ solvation. Furthermore, comparison of pulse EPR data with small angle scattering and THz calorimetry data might appear very interesting. Importantly, new EPR method to determine local biopolymer density will be presented, which might appear an efficient support for SAXS/SANS based determination of conformational ensembles of intrinsically disordered biomolecules.

About the speaker
[Biographical information about the speaker].

Meet the speaker
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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*: [link] (Meeting ID: [XXXXXXXXX], Password: [XXXXXXX])

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
Super-resolution microscopy has opened new possibilities for visualizing chromatin architecture in situ at nanoscale resolution. Leveraging quantitative super-resolution imaging, we revealed the heterogeneous nature of nucleosome folding and demonstrated that chromatin structure at both nano- and meso-scales is highly plastic, dynamically remodeling in response to chemical and mechanical cues in health and disease. By combining biologically interpretable feature extraction with machine learning, we further showed that cells can be accurately classified into distinct states based solely on their multi-scale chromatin organization, while also identifying the specific chromatin features that drive classification, thus offering mechanistic insight into cell-state regulation.

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.