Dr. Roy van der Meel
Roy van der Meel is a biomedical engineer specialized in nanomedicine and RNA therapeutics. After obtaining a PhD from Utrecht University under guidance of Wim Hennink and Gert Storm, and a postdoc appointment at the UMCU in Raymond Schiffelers’ lab, he moved to Pieter Cullis’ lab at the UBC in Vancouver, Canada. During his 3.5-year postdoctoral tenure, he gained extensive experience with developing lipid nanoparticle (LNP) technology that has enabled the approval of the first siRNA therapeutic Onpattro® and the COVID-19 mRNA vaccines. In 2019, he was recruited to TU/e Willem Mulder and appointed Assistant Professor in the Precision Medicine group. His current research focuses on establishing platform nanotechnology for delivering RNA therapeutics to specific immune cells and regulating the innate immune response. He has co-authored over 50 publications in leading nanotechnology-focused journals including Nature
Title: Engineering platform nanotechnology for RNA delivery to immune cells
Nucleic acid therapeutics are revolutionizing healthcare via gene inhibition, addition, replacement or editing. However, nucleic acid-based drugs require chemical modifications and sophisticated nanotechnology to prevent their degradation, reduce immunostimulatory effects, and ensure intracellular delivery. Lipid nanoparticle (LNP) technology is the current gold standard platform that facilitated the first siRNA drug Onpattro’s clinical translation and the COVID-19 mRNA vaccines. Nevertheless, current LNP systems are mostly suited for vaccine purposes following local administration or hepatic delivery following intravenous administration. To unleash RNA’s full therapeutic potential, this talk will demonstrate modular nanoplatform technology for systemic nucleic acid delivery to immune cells in hematopoietic organs using apolipoproteins developed in the Precision Medicine group at TU/e.
Utrecht University – The Netherlands
Daniel Hurdiss investigates the three-dimensional structure of viral proteins and how this relates to their function. After studying for a Microbiology degree at the University of Leeds (UK), Daniel stayed on to do his PhD in the Astbury Centre for Structural Molecular Biology. During this time, he used cryo-electron microscopy to study the structure of pathogenic viruses and their interaction with cellular receptors. After he obtained his doctoral degree in 2018, he moved to Utrecht University, where he uses structural, biochemical, and molecular virology techniques to study the lifecycle of pathogenic viruses. By understanding how viruses enter, hijack and escape host cells, he aims to make significant contributions to our understanding of viral pathogenesis and the development of effective antiviral treatments.
Title: Coronaviruses: Past, Present and Future.
Dr. Sandrine Etienne-Manneville (GSLS lecture)
Sandrine Etienne-Manneville is a CNRS research director at the Institut Pasteur, where she heads the Cellular Polarity, Migration and Cancer unit. She studied at the Ecole Normale Supérieure de Paris and obtained a PhD in Immunology, working on the mechanisms by which immune cells enter the central nervous system. During her post-doc in London she initiatied the study of the migration of astrocytes, nerve tissue cells involved in numerous brain pathologies. In 2006, she became group leader at the Institut Pasteur, where she continued to study the migration of normal astrocytes and astrocyte derived tumors, gliomas. Named Chevalier de l’Ordre du Mérite and also elected EMBO member, her work has also been recognized by numerous national and international awards, including the René Turpin award for cancerology from the French science academy in 2022.
Her demonstration that adhesion molecules activate conserved polarity pathways, such as the Cdc42-Par6-aPKC pathway, has been a major breakthrough in the field (Cell 2001, Nature 2003, JCB 2010a). The study of polarity signaling in migrating astrocytes revealed the role of major tumour suppressors (APC(Adenomatous Polyposis Coli), LKB1, PTEN, Scrib and Dlg) in the control of cell polarity, leading to the now commonly accepted hypothesis that loss of polarity could directly promote oncogenesis (JCB 2005, Curr Biol 2006, Hum Mol Gen 2008, EMBO 2011, Elife 2015). More recently, her group has revealed that cadherins control front-to-rear polarization to direct astrocyte migration, broadening the role of adherens junctions in polarity and migration to non-epithelial cells (JCB 2009, JCS 2011, Nat Cell Biol 2014). The astrocyte and glioma models have proven to be ideal to demonstrate the essential role of microtubules and intermediate filaments in cell polarization and directed migration. This work also led to the development of new imaging techniques, and to fruitful collaboration with mathematicians and biophysicists to investigate cytoskeletal crosstalk in the context of cell mechanics and mechanotransduction (J Cell Biol, 2017, Biomaterials 2021, Nat. Materials 2022). This model has paved the way to a better characterization of cytoskeletal interplay, that she will describe during her lecture.
Title: Cytoskeletal crosstalk in cell adhesion and migration
Cell migration is essential during development and in the adult where it participates in immune responses, tissue renewal, wound healing as well as cancer turning a locally growing tumor into a live-threatening disease. Our research objective is to elucidate the intricate molecular mechanisms governing cell migration in both health and disease. Although the process of migration varies with the cell type, the cell environment and the molecular cues triggering and regulating cell movement, the cytoskeleton consistently plays a central role in promoting cell migration and invasion. The different elements of the cytoskeleton, actin microfilaments, microtubules and intermediate filaments organize from the front to the back so that cells can adhere to the substrate, contract and retract while also interacting with their neighbours. The contribution of actin in promoting cell protrusion, adhesion, and in cell rear contractility has been extensively studied. Acto-myosin stress fibers anchored at focal adhesions generate the traction forces required for movement. However, not only actin, but also microtubules and intermediate filaments interact with focal adhesions. We will delve into how these distinct cytoskeletal networks contribute their unique mechanical and signaling properties to the regulation of focal adhesion dynamics, acto-myosin contractility, and the overall process of mesenchymal cell migration.
Amsterdam UMC (AMC)– The Netherlands
René Lutter is trained as a protein biochemist at the University of Amsterdam and Sanquin (with Dirk Roos, Mic Hamers, Joseph Tager) on a topic related to innate immunology. He then moved to MRC Lab Molecular Biology in Cambridge, UK, with John Walker, and managed to develop the procedure for crystallizing the mitochondrial ATPase. This enabled them to determine its structure, for which the 1997 Nobel Prize was awarded to John. Subsequently, René returned to Amsterdam at the AMC to set up a research lab for lung diseases and a diagnostic lab. His studies focus on biological mechanisms and the approach is translational, involving studies with patients and healthy individuals. He has been active within national (NRS, Astmafonds) and international (European Respiratory Society) bodies, served as associate editor for various journals, as expert on several advisory boards, as reviewer for various funding bodies, and more.
Title: From chronic inflammation and viral induced exacerbations in asthma to metabolic stress in post-Covid
Asthma affects about 340 million people, about 10% of whom are affected severely. Although treatment options have expanded considerably, treatments are not always effective, are costly and do not lead to a cure. We have been working on the mechanism underlying chronic inflammation in asthma, and how a respiratory viral infection worsens airway inflammation. The mechanism that we have found, also explains the heterogeneity in asthma. Our studies with viral challenges in patients and healthy individuals have led us to also assess effects of SARS CoV2 infection, which ultimately led us to the concept of metabolic stress in patients with post-acute symptoms of Covid.
Imperial College London – England
Bacterial infections are a leading cause of human mortality and have had a major influence of the evolution of the human immune system. As bacteria cause minor to life-threatening infections and trigger inflammatory diseases such as sepsis when the responses of the innate immune cells are imbalanced, rebalancing the innate immune response could be an effective strategy to prevent bacterial diseases. Our research investigates the molecular mechanisms that fine-tune innate immune responses and characterises how bacterial pathogens exploit these mechanisms to cause infection or trigger inflammation. More specifically, we study the structural, functional and biological properties of inhibitory immune receptors on innate immune cells. Inhibitory immune receptors regulate the activity of our cells to maintain immune balance. They are like brakes on a car, that are essential to regulate immune cell activity to prevent them going into overdrive. More specifically, they recognise endogenous ligands and produce intracellular signals that dampen cell activity. They are also known to be targeted by human pathogens as a means to hijack immunosuppressive signalling to promote immune evasion and infection.
Our research is aligned into two broad themes,
1) Inhibitory Receptors in Innate Immunity. As there are many inhibitory receptors for which we poorly understand their role in human biology, we ask; Where and when are inhibitory receptors expressed? What are the endogenous ligands of inhibitory receptors? How do inhibitory receptors signal? What are the immunomodulatory functions of inhibitory receptors?
2) Inhibitory Receptors in Bacterial Infections. As bacteria are known to interact with inhibitory receptors, we ask; Which bacteria interact with human inhibitory receptors? How do bacteria interact with inhibitory receptors? What is the impact of the interactions on antibacterial responses? How does this influence the outcome of infection?
Title: An Inhibitory Immune Receptor is the Key Bacterial Receptor in Puerperal Sepsis
Amsterdam UMC (VUmc)– The Netherlands
Since the start of her career Prof. dr. van Egmond has studied the function of antibodies, with emphasis on understanding the role of immunoglobulin A (IgA) in physiology and pathology. Her research also addresses (1) the contribution of abnormal antibody responses in chronic inflammation and autoimmunity and (2) monoclonal antibody therapy of cancer. Prof. dr. van Egmond’s research is highly translational and she has a cross appointment with the Department of Surgery and the Department of Molecular Cell Biology and Immunology at Amsterdam UMC, to facilitate the rapid progression of pre-clinical findings into clinical applications. Prof.dr. van Egmond is the spokeswoman of the Dutch Society for Immunology, and since the COVID-19 crisis she has an active role in providing information on the immune system and vaccines to the general public.
Title: Immunoglobulin A: Trojan horse or magic bullet?
Immunoglobulin A (IgA) is the most prevalent antibody at mucosal sites, and it is now increasingly accepted that it has an important role in mucosal immune defense by preventing invasion of pathogens. We previously demonstrated that IgA is a very potent stimulus to trigger myeloid immune cell activation, most notably as it induces neutrophil migration through interaction with the IgA Fc receptor (FcaRI). This will be beneficial in (mucosal) infections, as potential infectious threats can be cleared. However, abnormal or excessive IgA immune complexes induce disproportionate neutrophil recruitment and activation, ultimately leading to significant tissue damage. In this presentation the contribution of auto-IgA in pathology of autoimmune diseases will be addressed as well as potential to unleash the destructive capacity of neutrophils as attractive opportunity for future anti-cancer therapies.
Photo by: Janne van de Wijer
Provided by sponsoring of Miltenyi Biotec
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