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PROGRAM Longevity World Forum

Ubiquitin and Autophagy networks in regulation of health and disease

Speaker: Prof. Ivan Dikic
Institution: Molecular Signaling Lab, Goethe University, Frankfurt, Germany

Place: Jerónimo Forteza conference room, CIPF

Abstract: The human body is in a continuous state of repair and renewal, from breaking down and reusing damaged or excess cell parts via the process of autophagy. The endoplasmic reticulum (ER) in the cell cytoplasm, critical to the synthesis and transport of cellular components, is no exception. ER-phagy is a major driver of ER remodelling, and ER-phagy receptors play central roles in this process. Loss-of-function mutations in ER-phagy receptors (FAM134b) result in autosomal recessive hereditary sensory and autonomic neuropathy (HSAN) in humans and dogs.

Within the last decades, several ER-resident membrane-shaping proteins with central reticulon homology domains (RHD) have been associated with hereditary axonal disorders as well, i.e. ATL1, ATL3, REEP1 and REEP2, SPAST, RTN2, and ARL6IP1. They can also cause hereditary spastic paraplegia/HSP, a neurodegenerative disorder characterized by progressive leg spasticity alone or in combination with loss of sensory and pain perception (HSAN). The underlying mechanisms of RHD-containing proteins functions as well as their contribution to pathogenesis of HSP and HSAN neuropathies remain largely elusive. I will discuss the role of ubiquitination and autophagy in controlling ER-phagy receptor clustering and efficient ER remodelling and renewal. Structural models of RHDs and intrinsically disordered regions (IRDs) located in the cytosolic loops of ER-phagy receptors will be elaborated. Moreover, mouse genetic data reveal how defects in ER-phagy pathways lead to neuronal cell death and sensory and motorneuron neuropathies.

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Speaker: Dr. Tambet Teesalu
Institution: Laboratory of Precision and Nanomedicine, University of Tartu, Estonia

Place: Jerónimo Forteza conference room, CIPF

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Emulsions as a tool to study tissue mechanics in vitro and in vivo

Speaker: Lea-Laetitia Pontani
Institution: Jean Perrin Laboratory, Sorbonne University, Paris, France

Place: Jerónimo Forteza conference room, CIPF

Abstract: We use biomimetic emulsions to study the physical basis of collective remodeling during development. Indeed, emulsions made of oil droplets in water can be tailored to mimic the minimal mechanical and adhesive properties of cells in biological tissues. This reductionist approach allows us to study the mechanical properties of tissues in a simplified framework in which the inherent biological complexity due to intracellular regulations is bypassed.

We focus on the interplay between adhesion and mechanical forces and how this interplay regulates the emergence of tissue architecture during morphogenesis. To do so, we study the elasto-plasticity of these emulsions as a function of interdroplet adhesion through microfluidici approaches. We show that adhesion alone is able to guide the emergence of structuration in adhesive emulsions when they are submitted to mechanical constraints.

In parallel to this in vitro approach, droplets can be used to probe cellular forces inside biological tissues. Indeed, droplets can be made soft enough to probe forces exerted by cells or tissues: knowing their surface tension, it is then possible to quantify the local exerted stress from their observed deformation. We are currently using droplets to unravel the role of the extracellular matrix in the mechanical coupling of cells and tissues during morphogenesis.

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With support from the Generalitat Valenciana, AMPER-07/2024 and CIAORG/2023/147

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Speaker: Dr. Irene Casanova Salas
Institution: Prostate Cancer Translational Research Team. Vall Hebron Institute of Oncology (VHIO). Barcelona, Spain.

Place: Jerónimo Forteza conference room, CIPF

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