EMBL Seminars

Abstract
 

Genotype-Environment Integration Across Generations: A Plant Case Study 

Developmental plasticity in response to environmental conditions is a characteristic property of organisms that allows for substantial adaptive adjustment at the individual level. Evolutionary biologists have generally accounted for such plasticity by assuming that the individual's responses to its environment are genetically pre-programmed. Studies of transgenerational plasticity in the annual plant Polygonum persicaria provide new insights that challenge this view. Experimental tests of contrasting parental light and soil moisture treatments show that parental and grandparental conditions influence the phenotypes expressed by progeny. Moreover, conditions during the parental generation affect how progeny respond developmentally to their own environments. Individual phenotypes thus reflect a complex developmental integration over time of current and ancestral environmental signals. Because these developmental integration trajectories vary genetically (i.e., as multi-generation Genotype x Environment interactions), the integration process itself can potentially evolve.

About the speaker
Professor of Environmental Studies and Biology at Wesleyan University

Abstract
The medial prefrontal cortex (mPFC) is at the core of numerous psychiatric conditions, including fear and anxiety-related disorders. Whereas an abundance of evidence suggests a crucial role of the mPFC in regulating fear behaviour, the precise role of the mPFC in this process is not yet entirely clear. While studies at the single-cell level have demonstrated the involvement of this area in various aspects of fear processing, such as the encoding of threat-related cues and fear expression, an increasingly prevalent idea in the systems neuroscience field is that populations of neurons are, in fact, the essential unit of computation in many integrative brain regions such as prefrontal areas. What mPFC neuronal populations represent when we face threats? To address this question, we performed over the years electrophysiological recordings and calcium imaging of neuronal population in the dorsal mPFC while mice faced threat-predicting cues eliciting defensive behaviours. I will present some results demonstrating the dynamic encoding at the neuronal population level of danger representation in dmPFC networks and how these dynamics constrain learned defensive behaviours.

Abstract

Organelles such as centrosomes, nucleoli or mitochondria perform well-known common functions in all cell types. I will discuss their surprisingly large degree of different composition in the context of development, disease and direct reprogramming. For example, the centrosome of human neural stem cells differs by more than half of its proteome from the one in neurons (O’Neill et al., Science 2022). Such cell type-specific composition also explains why some ubiquitous proteins have organ-specific defects, when mutated in patients, as they are only at a specific organelle in specific cell types. I will explain this for the splicing protein PRPF6 that plays specific roles at the centrosome in neural stem cells which is relevant for the disease periventricular heterotopia. I will then turn to organellar heterogeneity in direct neuronal reprogramming and discuss the role of mitochondria heterogeneity in this process and how to overcome hurdles in this conversion process due to late change of the mitochondrial proteome to a neuronal identity. This will bring us to human glia-to-neuron reprogramming where we discovered that the unfolded protein response is a hurdle elicited by mitochondrial dysfunction during the reprogramming process. Its inhibition results in much improved reprogramming allowing even to convert glia of patients with mitochondrial dysfunction. I will then proceed to discuss recent unpublished data on how to bring human glia-to-neuron reprogramming to an in vivo setting. Taken together, a better understanding of the distinct composition of organelles in a highly cell type-specific manner in development, helps treating disease and improving repair processes.   

Zoom details: https://www.embl.org/internal-information/updates/distinguished-visitor-lecture-magdalena-gotz/ 
 

Abstract
Chromatin regulators are typically multi-protein complexes that contribute to transcription regulation by modulating the chemical and structural features of chromatin. Polycomb repressive complex 2 (PRC2) is a histone methyltransferase (HMTase) specific for the methylation of lysine 27 of histone H3 (H3K27me3) that is associated with transcriptional repression. 

Multiple structural studies have together established key characteristics of PRC2 engagement with chromatin and its localized regulation. In particular, single-particle cryo-electron microscopy (cryo-EM) has been instrumental in elucidating how PRC2 integrates chromatin features to adapt its catalytic activity in response to the local chromatin state. Not only is PRC2 a prime example for recruitment and regulatory mechanisms of chromatin regulators, it also showcases the technical challenges posed to the structural investigation of these factors, particularly in complex with chromatin substrates. Similar to other chromatin complexes, PRC2 requires dedicated sample preparation and stabilization strategies to obtain a sample amenable to structural analysis by cryo-EM. Therefore, I will use our work on PRC2 to elaborate on some of the sample optimization approaches that may be required for studying delicate and challenging samples.  

Abstract

The adaptive immune responses mediated by T lymphocytes play a critical role in host protection against pathogens and tumors. Following activation by antigens, naïve CD8+ T lymphocytes establish specific heritable gene expression programs that define the progression to long-lasting memory or to short-lived effector subsets.
Our findings have defined a critical role of Suv39h1-dependent gene silencing in the establishment and maintenance of memory CD8+ T cell stemness, plasticity during infection. We have also recently examined CD8 + T cell heterogeneity during the different stages of differentiation, by developing an integrative approach involving the combined analysis of chromatin dynamic changes and gene expression profiles. These results establish a transcriptional “map” during CD8+ T cell lineage commitment, highlighting new interclonal relationships during the different stages of CD8+ T cell differentiation. Our findings reveal a pivotal role of H3K9/heterochromatin structure to confer specificity and to gene regulation during T cell fate determination. Recent results and new perspectives will be discussed in the context of long-term memory.

Christian Tidona is a scientist entrepreneur and founder of the BioMed X Institutes in Heidelberg, Germany and New Haven, Connecticut. He studied biology and received his doctoral degree in natural sciences from the University of Heidelberg. Throughout his career, his focus was always to seed innovation at the interface between academia and industry. Christian is co-founder of BioRN in Heidelberg, the cluster management organization at the heart of one of the strongest biomedical innovation hubs in Europe, co-founder of the Heidelberg Institute for Stem Cell Technology and Experimental Medicine HI-STEM, and member of the Board of Directors of Yeda Research and Development, one of the world's most renowned technology transfer organizations at the Weizmann Institute of Science in Israel. Christian is married and father of two children.

The event will take place in-person (Heidelberg, Large Operon) and online - we ask all participants to register using the link below, and indicate whether they will attend in-person or online.

https://embl-org.zoom.us/webinar/register/WN_3ZVNZQ5gQXO-wR2efB79Nw#/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) or the “raise your hand” function and turn on your microphone.

Abstract
Understanding how cells translate extracellular cues into specific patterns of gene expression is one of the major goals of modern neurobiology. Neurons are cells with a complex morphology, which maintain their cellular structure through the compartmentalized expression of proteins essential for growth and plasticity. Asymmetric localization of RNA is an evolutionarily conserved mechanism that allows spatial restriction of protein synthesis to specific cellular compartments. Incorrect processing and delivery of mRNA causes developmental defects and severe human neurological disorders. In neurons, mRNA transcripts are transported to both dendrites and axons where they are rapidly translated in response to stimuli. This talk will explore how transcripts localized in sympathetic neuron axons are transported, processed and translated in response to neurotrophins. Special emphasis will be given to the epigenetic modifications of the RNA of targeted axons and how they may determine the transcripts fate. I will also discuss our recent important findings indicating that at least some axonal RNA transcripts interact with the signalling endosomes and other organelles, generating a signalling mechanism that regulates the spatial expression of genes essential for neuronal survival and axon growth. 

Please register to attend: https://embl-org.zoom.us/webinar/register/WN_ygrUsfRNTRy4Y-hNJUHujQ

More information on EMBL Skills & Careers Webinars: https://www.embl.org/about/info/embl-fellows-career-service/#Careerwebinars

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.

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.

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*: [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
[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.