Our understanding of the ubiquitin system is at a transformative moment – we are beginning to unravel its function in connection to its physiological roles with profound implications for many severe diseases. Initially discovered as a tag of cytosolic proteins for proteasomal degradation, the ubiquitin system is now recognized as a master regulator of cellular signaling, well beyond protein turnover. Ubiquitination and its reversal by deubiquitination provide dynamic control over a vast array of signaling pathways, enabling cells to finely tune the intensity and duration of signaling responses.

While some signaling roles are indeed related to ubiquitin’s degradative capacity – such as the activation of the transcriptional master regulator of inflammation, NF-κB, via degradation of its inhibitor IκB – most signaling-related functions of the ubiquitin system depend on non-degradative ubiquitin chains. These chains act as scaffolds, enabling the assembly of highly specific protein complexes that first initiate, then propagate and, finally, terminate crucial pathways of cellular signaling.

This conference shifts the spotlight from structural details to biological function. Together, we shall explore how the ubiquitin system orchestrates signal transduction under physiological conditions, what happens when this regulation breaks down and how this knowledge can be harnessed to develop a new generation of exquisitely specific and highly effective medicines. From cancer and chronic inflammation to autoimmune and neurodegenerative diseases, the therapeutic potential of targeting the ubiquitin system is near endless.

We envision this meeting as the premier forum for showcasing the most innovative and translational research in ubiquitin biology. It will serve as a catalyst for discussions on emerging therapeutic strategies and as a hub for collaboration across academia and industry.

A message from our Chairs... "The field of ubiquitin biology is one of the most vibrant and rapidly advancing areas in biomedicine. The discovery that powerful immunomodulatory drugs (IMiDs), including thalidomide and its analogues lenalidomide and pomalidomide, exert their effects by engaging ubiquitin-mediated degradation of critical disease-relevant factors has galvanized the field. Inspired by this mechanism, the development of PROTACs (proteolysis-targeting chimeras) is now a central focus in drug discovery across the pharmaceutical industry, aiming to eliminate targets previously regarded as ‘undruggable’.

The impact of the field of ubiquitin biology has been and still is profound. This is perhaps best exemplified by the award of several Nobel Prizes for work elucidating how the ubiquitin system governs proteasomal degradation, the cell cycle and the cellular response to hypoxia.

Together, we shall explore how ubiquitin orchestrates the signaling circuitry of life – and how its dysregulation drives the pathogenesis of cancer, inflammatory disorders and neurodegeneration. The future of our field shines brighter than ever before. Join us in Portugal for what promises to be a truly exciting conference."

Confirmed Invited Speakers

Neal Alto (UT Southwestern)
THE ROLE OF UBIQUITIN IN HOST-PATHOGEN INTERACTIONS
Eric Baehrecke (UMass Chan Medical School)
COORDINATED REGULATION OF UBIQUITIN-DEPENDENT AND -INDEPENDENT CLEARANCE OF ORGANELLES
David Beck (NYU School of Medicine)
VEXAS SYNDROME, UBA1 AND AUTOINFLAMMATION
Alessio Ciulli (University of Dundee)
TARGETED PROTEIN DEGRADATION: STRUCTURE AND MECHANISM
Ivan Dikic (Goethe University Frankfurt)
UBIQUITIN-DEPENDENT METALLOPROTEASE SPRTN PREVENTS PREMATURE AGING AND EMBRYONIC LETHALITY
Paul Elliott (University of Oxford)
SPECIFICITY WITHIN THE UB/UBL CONJUGATION PATHWAYS
Adolfo Garcia-Sastre (Icahn School of Medicine at Mount Sinai)
IMPACT OF UFMylation DURING INFLUENZA VIRUS INFECTION
Alexander Gitlin (Memorial Sloan Kettering Cancer Center)
INDEPENDENT MECHANISMS OF INFLAMMATION AND MYELOID BIAS IN VEXAS SYNDROME
Sudan He (Chinese Academy of Medical Sciences)
RIPK1 UBIQUITINATION LICENSES TNF-INDUCED CELL DEATH
Stefan Knapp (University of Frankfurt)
STREAMLINING THE DEVELOPMENT OF NEXT GENERATION PROTACs
Elke Krüger (University of Greifswald)
THE AMBIGUOUS ROLE OF PROTEASOME HETEROGENEITY: LESSONS LEARNT FROM RARE PROTEASOMOPATHIES
Yogesh Kulathu (University of Dundee)
Gianmaria Liccardi (University of Cologne)
PERTURBED LUBAC–DUB INTERACTION: A PATHOPHYSIOLOGICAL SURPRISE IN TWO ACTS
Sonja Lorenz (MPI Göttingen)
UNDERSTANDING AND MANIPULATING UBIQUITIN LIGASE SPECIFICITY
Nieves Peltzer (University of Stuttgart)
A LINEAR UBIQUITIN CODE FOR FITTER FAT
Felix Randow (MRC Laboratory of Molecular Biology)
UBIQUITYLATION OF NON-PROTEIN SUBSTRATES: MECHANISMS AND IMPLICATIONS
Michael Rapé (University of California, Berkeley)
ACTIVATION OF UBIQUITYLATION AND MITOCHONDRIAL FUNCTION BY SMALL MOLECULES
Eva Rieser (University of Cologne)
NON-CANONICAL UBIQUITIN LINKAGES IN IMMUNE SIGNALLING
Rahul Samant (Babraham Institute)
DIVERGENT POST-UBIQUITYLATION PROTEOSTASIS STRATEGIES IN CELLULAR SENESCENCE AND AGEING
Sichen (Susan) Shao (Harvard Medical School)
INSIGHTS INTO ER PROTEIN QUALITY CONTROL
Sylvie Urbé (University of Liverpool)
TARGETING AND HARNESSING DUBs TO MODULATE PROTEIN AND ORGANELLAR QUALITY CONTROL
Domagoj Vucic (Genentech)
CRITICAL ROLE OF UBIQUITINATION IN INFLAMMATORY CELL DEATH
Helen Walden (University of Glasgow)
DISCOVERY OF A FANCD2-INTERACTING PROTEIN MOTIF (DIP-box) LINKING DNA DAMAGE RESPONSE PROCESSES

Target Audience

This conference will appeal to researchers who are particularly interested in the diverse functions of the ubiquitin system, both in normal physiology and a whole range of pathologies associated with abnormal ubiquitin signaling. Naturally this target profile will bring together researchers from both academia and the pharmaceutical industry who want to be up to speed regarding the most recent developments in the fascinating and fast developing field of ubiquitin biology.

Learning Objectives

•    To be on top of the field regarding the functions and uses of the ubiquitin system.
•    To comprehend how the ubiquitin system affects health and disease.
•    To understand how the ubiquitin system is harnessed in the development of an entirely new class of therapeutics which allow the targeting of the “undruggable”.

Educational Need

We are witnessing a paradigm shift in our understanding of the ubiquitin system – not only as a mechanism for protein degradation but as a central regulator of cell signaling and disease. The ubiquitin system’s ability to dynamically modify signaling proteins through ubiquitination and deubiquitination allows for exquisite control over key biological processes. When this regulation is disrupted, the consequences are severe, contributing to cancer, inflammatory and auto-immune diseases, as well as neurodegenerative disorders.

The field’s complexity and rapid evolution present an urgent educational need. Many clinicians and scientists are unfamiliar with the system’s full functional scope, especially its growing relevance to therapy. Drugs such as IMiDs (e.g., lenalidomide) and PROTACs exploit ubiquitin-mediated degradation and are reshaping modern medicine. Yet, their mechanisms remain poorly understood outside specialized circles.

With this conference we aim to close this gap. Rather than focusing on structure alone, we will combine structure with function and therapeutic relevance of the ubiquitin system. Sessions will cover new discoveries in fundamental physiological mechanisms and of pathological consequences of dysregulation of the ubiquitin system and novel therapeutic strategies emerging therefrom as well as from the application of ubiquitin-mediated target degradation to the targeting of what was, until recently, considered the “undruggable” proteome.

Our goal is to equip researchers, clinicians and students alike with a deeper understanding of how ubiquitin shapes cellular behaviour – and how this knowledge can, in turn, be applied to meet urgent medical needs. This educational mission is more critical now than ever.