Invited speakers:
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Stein Aerts is Professor at KU Leuven, VIB scientific director and group leader at the Flemish Institute for Biotechnology (VIB), website https://aertslab.org/
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Isabelle Billas boasts over 20 years of expertise in nuclear receptors, specializing in deciphering the mechanisms of transcription regulation by steroid nuclear receptors through structural methods and evolutionary analyses. Her prolific publication record includes several high-impact journals, such as Nature, EMBO Journal, Nature Communications, Science Advances, PNAS, Frontiers in Endocrinology, Journal of Steroid Biochemistry and Molecular Biology, and PLoS Genetics. Dr. Billas is highly skilled in X-ray crystallography and biophysics and has contributed to the cryo-EM structure determination of the ecdysone nuclear receptor complex. She has recently incorporated single-particle electron microscopy for the structural analysis and 3D reconstruction of complexes associated with human steroid receptors. Recently, she joined Dr. G. Travé’s team at IGBMC, leveraging their expertise in quantitative interactomics and proteomics to enhance her structural research.
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Vanessa Dubois is Assistant Professor in Physiology and Endocrinology at Ghent University in Belgium. She obtained a PhD from the KU Leuven in 2015 focusing on the cellular and molecular mechanisms underlying the anabolic effects of androgens on the musculoskeletal system. She next joined the Pasteur Institute of Lille in France as a postdoctoral researcher to further explore how endocrine receptors control metabolic processes and the alteration thereof in liver dysfunction. In 2022, she founded the Basic and Translational Endocrinology (BaTE) unit at Ghent University. Her current research focusses on unravelling how sex hormone receptors regulate (sex-specific) physiological processes in metabolic tissues like liver and skeletal muscle, and how this regulation is reshaped in clinically relevant situations such as metabolic dysfunction-associated steatotic liver disease (MASLD) and gender-affirming therapies.
Website: https://research.ugent.be/web/person/vanessa-dubois-0/nl
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Dr. Erin Faught received her PhD from the University of Calgary (Canada) in 2019 where she studied the physiological significance of glucocorticoid (GR) and mineralocorticoid (MR) receptor activation. As important modulators of the stress response, these receptors are conserved throughout vertebrate evolution, and using zebrafish as a model, she worked to uncover novel roles of MR and GR on metabolic function. As a recipient of a Marie Curie post-doctoral fellowship, she relocated to the Netherlands (Leiden University) where she investigated how MR/GR interaction modulated immune system development. With a post-doctoral fellowship from the Canadian Institutes of Health Research (CIHR), this work was extended to determine the immunological significance of these receptors and their interaction. Recently, Erin was the recipient of a NWO VENI grant and is working to uncover the molecular mechanisms associated with short-term versus long-term stress and how this might be used to mitigate the negative effects of stress.
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Felix Hausch is professor for structure-based drug research at the Technical University Darmstadt. He is a recognized expert for the chemical biology of immunophilins (mainly FKBPs) and has discovered the SAFit class of selective FKBP51 ligands. He has authored 89 publications (incl. Nat Chem Biol, Angew Chem, JACS and >10 accepted patent families. He is speaker of the LOEWE consortium TRABITA, Core team member of the Zukunftscluster PROXIDRUGS, coordinator of the BMBF consortia iMIP and 51TaValP, co-coordinator of the VIP+ consortium Fit4Fat and of the ANR/BMBF consortium SIAM. Felix Hausch received his PhD from the Free University Berlin in 2000, gained postdoc experience at Stanford University and biotech industry in Zurich (ESBATech AG, 2 years), and was group leader at the Max-Planck Institute of Psychiatry and lecturer at the LMU (Munich, 2005-2016).
Website:
https://www.tu-darmstadt.de/synbio/synbio/mitglieder_1/mitglieder_details_116736.en.jsp
Heterodimerization of glucocorticoid and mineralocorticoid receptors is crucial for cortisol-mediated behaviour in zebrafish.
Erin Faught and Marcel J.M Schaaf
Institute of Biology, Leiden University, 2333 CC Leiden, The Netherlands
Stress and the attendant rise in cortisol mediates a suite of physiological and behavioural responses essential for stress adaptation. Cortisol acts to mediate these effects through the activation of glucocorticoid (GR) and/or mineralocorticoid (MR) receptors. These receptors are highly conserved transcription factors that bind to glucocorticoid response elements (GREs) in regulatory regions of target genes by creating dimers with either the same receptor (homodimerization) or each other (heterodimerization). Despite well-established behavioural responses in zebrafish showing that GR and MR are necessary for cortisol-induced hyperactivity, whether receptor heterodimerization mediates these behavioural outcomes is unknown. Here we tested the hypothesis that GR and MR heterodimerization was essential for cortisol-induced hyperactivity. Using site-directed mutagenesis, we established salt-bridge mutant receptors that could selectively dimerize through their DNA-binding domain. These mutated receptors were then injected into zebrafish embryos lacking both MR and GR (MGR-knockout). Subsequent behavioural analysis revealed that only under conditions of GR/MR heterodimerization, could cortisol-induced hyperactivity be rescued. To investigate the molecular targets, we next performed RNA-sequencing, which showed that GR/MR heterodimerization regulated the type II metabotropic glutamate receptor, metabotropic receptor 3 (mGluR3). Indeed, treatment with a type II metabotropic receptor agonist restored cortisol-induced hyperactivity to baseline. Furthermore, disruption of a putative GRE site upstream of mGluR3 led to an abolishment of cortisol-induced hyperactivity. Taken together, this study establishes the behavioural significance of GR/MR heterodimerization and that combined GR and MR signalling is central to the neurobiological adaptation to stress.
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Program
09.00-09.55 Registration, coffee, poster mounting
Session 1 Chaired by: Carlie Devries
10.00-10.05 Welcome by Frank Claessens
10.00-10.40 Liver zonation by deep learning of single cell data
Stein Aerts
10.40-10.55 Selected abstract
10.55-11.30 Coffee break
Session 2 Chaired by: Saskia van Mil
11.30-12.05 Sex differences in the hepatic response to repeated metabolic challenges
Vanessa Dubois
12.05-12.20 Selected abstract
12.20-12.35 Selected abstract
12.35-14.00 Lunch and poster session
Session 3 Chaired by: Karolien De Bosscher
14.00-14.35 Zebrafish as a model to study GR/MR
Erin Faught
14.35-15.10 Intracellular GR-interaction mapping
Felix Hausch
15.10-15.25 Selected abstract
15.25-16.00 Coffee break
Session 4 Chaired by: Luc Brunsveld
16.00-16.15 Selected abstract
16.15-17.00 Structural biology of NRs
Isabelle Billas
17.00-18.00 Best poster awards, announcement of NRRN 2025 and drinks