EMBL Seminars

Abstract
Our research focuses on the role of RAF kinases in transmitting signals within the RAS-RAF-MEK-ERK (RAS/ERK) cascade. Hyperactivation of the RAS/ERK pathway caused by activating mutations in RAS and RAF is a major driver of tumor formation in ~30% of all cancers1. Improving our understanding on the regulation of the RAS/ERK pathway is of paramount importance for the development of next-generation therapeutics.  

The RAF family comprises three catalytically active isoforms (ARAF, BRAF, CRAF) and two pseudokinase isoforms (KSR1, KSR2), which adopts dimers conformation to activate RAF catalytic outputs2. Our goal is to investigate the molecular mechanisms governing the dimerisation of KSRs with RAFs. Our investigation uncovered an allosteric mechanism driving KSR1:BRAF heterodimerization and BRAF activation, which depends on MEK binding to KSR and on the interactions between the N-Terminal domains of KSRs and BRAF3. Additionally, we revealed how the scaffold proteins CNK and HYP potentiate this KSR-dependent mechanism through the formation of an unexpected CNK:HYP:MEK:KSR quaternary complex4.

Employing integrative structural biology techniques combining NMR, X-Ray crystallography and cryo-EM alongside biochemical analyses, we aim to deepen our understanding of the pivotal role of the pseudokinase KSR in regulating the RAF kinases, providing novel insights into the multi-layered regulation of the oncogenic RAS/ERK signaling pathway.

1Lavoie H et.al., Nat Rev Mol Cell Biol (2015) - 10.1038/nrm3979 
2Rajakulendran T et.al., Nature (2009) -10.1038/nature08314
3Lavoie H et.al., Nature. (2018) -10.1038/nature25478
4Maisonneuve P et.al., Nat Struct & Mol Biol (2024) -10.1038/s41594-024-01233-6

Connection details
Zoom*: https://embl-org.zoom.us/j/97170620085?pwd=LklFaC4gFmlJHvw5tMSbT2vqaKsaNV.1   
Webinar ID: 971 7062 0085
Passcode: 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
The inhibitor of kB kinase (IKK) is the master regulator of NF-kB signalling and plays a key role in the activation and regulation of inflammatory processes and innate immune response. Biochemically, IKK exists as different complexes comprising a shared catalytic core and variable regulatory subunits. Research in our team focuses on the dissection of the mechanisms of IKK-substrate interactions mediated by the catalytic core using biochemical, in cellulo and structural approaches. Results concerning the identification of a novel linear motif and its regulation, as well as the overall assembly of larger kinase-substrate complexes will be discussed during the talk.

Connection details
Zoom*: https://embl-org.zoom.us/j/97170620085?pwd=LklFaC4gFmlJHvw5tMSbT2vqaKsaNV.1  
Webinar ID: 971 7062 0085
Passcode: 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.

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Connection details
Zoom*: [https://embl-org.zoom.us/j/97077851213?pwd=7amfBr45hvPeJn3bSMzdtfudKIpC5C.1] 
*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
Cell mechanical forces play an increasingly well-appreciated role in tissue morphogenesis, wound healing, and collective cellular organization. Cells embedded in an extracellular matrix generate forces, sense the mechanical properties of their surroundings, and respond by changing their migration, orientation, and interactions with neighboring cells. In this talk, I will discuss our recent theoretical work, in combination with two distinct experimental systems, that show how collective cellular behaviors emerge through mechanically mediated interactions in soft biological materials.

I will first describe how cells interacting through deformable elastic substrates can communicate over long distances through the deformations they generate in the surrounding matrix. Such mechanically mediated interactions can drive spontaneous cellular alignment, cooperative force generation, and multicellular pattern formation relevant to tissue organization in vascular morphogenesis.

I will then discuss the role of fibrous extracellular matrices such as collagen and fibrin, whose mechanics are highly nonlinear due to fiber stretching, bending, and buckling. Using a minimal physical model, we investigate how microscopic fiber mechanics shape tissue-scale force transmission and collective cellular cooperativity. We demonstrate these ideas by measuring blood clot mechanics. Importantly, we show that compression-induced buckling of fibers can effectively screen force propagation, softening clots and lowering contractility. Together, these studies illustrate how the nonlinear mechanics and architecture of extracellular matrices regulate collective cell organization and tissue function.

Abstract
Public engagement is an important part of the research landscape for any scientist or researcher, especially those whose work is funded by public money. By engaging in two-way conversations with diverse groups of people, you can:
• Connect science and society through meaningful communication
• Inspire curiosity and promote informed scientific dialogue
• Support policy-making and accountability in publicly funded research

On top of all that, involvement in public engagement also enables you to develop communication, leadership and project-management skills, and to achieve more visibility for your work.

In this webinar, Sally Hall, Public Engagement Officer at EMBL, will offer an overview of the what, why and how of public engagement in practice, giving practical tips for how you can get involved, and highlighting the ways in which public engagement can enhance professional development and support your career journey, as well as bringing new insights to your research.

Registration
Please register to attend: https://embl-org.zoom.us/webinar/register/WN_TMo9LvC3TtuKXW_6W_IMVQ

 https://trincebio.com/

Abstract:

Access to the intracellular space remains a central challenge across molecular biology, cell engineering, and advanced imaging applications. Existing delivery methods often require trade-offs between efficiency, cell viability, flexibility, and scalability, limiting their broader applicability.

We introduce LumiPore, an intracellular delivery platform based on a photoporation approach, in which laser-activated LumiSense nanoparticles generate transient pores in the cell membrane. This enables controlled delivery of diverse molecular cargoes, including nucleic acids, proteins, antibodies, and imaging probes, while maintaining high cell viability and functionality, even in sensitive and difficult-to-manipulate cell types.

The talk will present the key principles behind the LumiPore technology and an overview of the workflow and the parameters that shape its performance. Demonstrated across a range of use cases in functional biology and imaging, including CRISPR-based assays, gene editing, and intracellular labeling, these results position LumiPore as a versatile tool for both discovery-driven and translational research.

Abstract
The study of bacterial swimming is one of the most classical and fundamental approaches to understanding motility at the cellular level. It helps us solve not only the biological puzzles of how microorganisms spread infections or communicate with each other, but also pave the way to "un-blackboxing" physical phenomenon far from equilibrium like anomalous diffusion and pattern formation. While bacterial motility has been well characterized in liquid environments, only little is known about how bacteria navigate complex environments mimicking their natural habitats like soil, mucus or tissues, where they generally face strong confinements and heterogenities. In this talk, I will discuss how we can combine experimental analysis using the soil bacterium Pseudomonas putida and active particle modeling to examine migration patterns of bacteria in disordered environments (agar gel), which leads to remarkable motility characteristics like transient subdiffusion and ergodicity breaking. Next, I will address another paradoxical question in this direction: how can bacteria perform chemotaxis in a confined environment, providing insights about the role of signaling in active transport. Finally, I will introduce a coarse-grained model that we are working on recently, where the non-reciprocal interplay of two chemicals, coupled with a Keller–Segel-like motility of microorganisms, leads to a prolific variety of patterns, ranging from different types of novel phase separation to travelling waves, breathing spots and spiral waves. ].

About the speaker
Agniva Datta is a doctoral researcher and physicist at the University of Potsdam in Germany. He works within the Institute of Physics and Astronomy and specializes in the fields of biological physics, statistical physics, nonlinear dynamics, and active matter.].

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.