LS² Annual Meeting 2025

Title of the talk:  Understanding the Life Cycle of α-Synuclein in Neurodegeneration

Research plans:

Parkinson’s disease (PD) is a common neurodegenerative disorder for which no cure currently exists. The aggregation of α-synuclein plays a crucial role in the onset, progression, spread within the brain, and neuronal death associated with PD. Consequently, much of the current PD research is focused on α-synuclein, with efforts aimed at directly targeting aggregated α-synuclein using anti-amyloidogenic compounds, antibodies or vaccines. Despite some early successes, PD remains a difficult condition to treat. At the same time, there is a growing recognition among researchers, industry professionals, and clinicians that discovering new drug targets relevant to PD could significantly speed up the development of effective treatments.

Proteins that regulate α-synuclein homeostasis are of particular interest in this context. In this proposal, I aim to identify the regulators and modulators of the α-synuclein “life cycle” and its homeostasis in both healthy and diseased states, using an unbiased, label-free, proteome-wide approach. To achieve this, I will employ a cutting-edge structural proteomics approach that combines limited proteolysis and mass spectrometry (LiP-MS). By identifying key interactors and pathways that govern the synthesis and processing of α-synuclein, we can compile a comprehensive resource of protein targets that regulate α-synuclein homeostasis, providing a valuable new toolbox for future PD treatment development.    

Title of the talk:  Aging, Cancer, and Space Travel: DNA-Damage Sequencing for Precision Health

Research plans: 

DNA is the fundamental template for genetic information but is inherently unstable and prone to diverse endogenous and exogenous chemical modifications, which drives aging, neurodegeneration, carcinogenesis, and chemotherapy drug action. My research focuses on elucidating the mechanistic and systems-level roles of DNA damage in human (patho)physiology and on developing biomarkers for personalized health, with an emphasis on aging, cancer, and neurodegeneration.

My future laboratory will employ cutting-edge technologies to sequence DNA damage in mammalian genomes with single-nucleotide precision, integrating these data with multi-omics and physiological measurements. This work will build on my postdoctoral studies, where I developed several DNA-damage sequencing methods, including: click-code-seq [1], which detects abundant forms of DNA damage, such as oxidized guanines and abasic sites; TRABI-Seq [2] which maps DNA breaks induced by the anticancer drug trabectedin, reflecting DNA repair activity; and methods [3, 4] to sequence DNA-alkylation products caused by smoking and chemotherapy.

I propose the following research projects, addressing the broad implications of DNA integrity in human health:

Project 1. Mechanistic DNA-Damage Biomarkers of Aging. Developing biomarkers of biological age is essential for discovering and testing drugs that can extend human health span and lifespan. DNA damage, a primary hallmark of aging, is causally linked to nearly all age-related phenotypic traits. I plan to create biomarkers implicated at the core of aging based on DNA-damage sequencing, identifying genomic loci where DNA damage is strongly associated with age and aging-related traits and diseases. These biomarkers will be validated using tissues from human donors and multiple mammalian species.

Project 2. DNA-Damage-Based Biomarkers for Precision Oncology. To enhance cancer treatment, I aim to identify biomarkers of anticancer drug efficacy and toxicity by profiling genome-wide DNA-damage patterns in tumor and non-tumor biopsies, cell lines, and organoids. Unlike indirect estimates of DNA repair activity derived from genomics, transcriptomics, or proteomics, DNA-damage profiling provides a direct functional readout of DNA-repair pathways, enabling more accurate predictions of treatment outcomes.

Project 3. The Role of DNA Damage in Brain Activity. DNA damage is a known driver of neurotoxicity in neurodegenerative diseases and has recently been implicated in normal brain function. I aim to map how DNA damage at specific genomic loci influences neuronal activity, providing new insights into the molecular mechanisms underlying both neurodegeneration and cognitive processes.

Project 4. DNA Integrity in Space: Adaptations and Adverse Effects. As humanity enters the Second Space Age, mitigating the accelerated aging, tumor formation, and neurodegeneration caused by microgravity and ionizing radiation becomes a critical challenge. I will validate DNA-damage biomarkers of biological age (developed in Project 1) for space biology by quantifying genome-wide DNA damage in cells and organoids exposed to simulated microgravity and ionizing radiation in laboratory setups, parabolic flights, and space missions. This research will facilitate the discovery of drugs to counteract the adverse effects of space travel.

Title of the talk:  Disorder, Order, and Life: Protein Self-Assembly in Cellular Organization, Disease, and Drug Discovery

Research plans: 

Life arises from the intricate assembly of disordered matter into organized structures. Understanding how simple biological components self-assemble into complex living systems remains one of biology’s most fascinating and fundamental challenges.

Over the past decade, the overarching goal of my research has been to uncover the fundamental principles by which proteins self-organize into complex macromolecular assemblies - also known as protein condensates - via processes like phase separation and aggregation. Through my work at ETH Zürich and the University of Cambridge, I have demonstrated that protein condensates play essential roles in regulating diverse cellular processes, including metabolism and stress responses. Moreover, I have uncovered evolutionarily conserved mechanisms that govern protein condensate formation and disassembly and described how their misregulation is linked to the development of neurodegenerative conditions like Alzheimer’s and Parkinson’s disease.

Building on this foundation, my future lab will integrate experimental and computational approaches to tackle three critical questions:

1.     Physiology: What are the physiological roles of protein condensates?

2.     Pathology: How do protein condensates contribute to disease?

3.     Therapeutics: How can we exploit protein self-assembly to tackle medical challenges?

To exemplify this vision, in this talk I will highlight MicroResist, my latest project that aims to exploit protein condensates to develop novel antibiotics. I recently discovered that several protein condensates possess intrinsic antibacterial properties. By combining pioneering microfluidic technologies with cell biology and biochemistry, my research team will: (1) characterize the physiological roles of these naturally occurring antibacterial condensates, (2) uncover the physico-chemical principles underlying their regulation and antibacterial activity, and (3) develop microfluidic-based ultrahigh-throughput platforms to generate and screen next-generation antibiotics inspired by antibacterial condensates.

Impact: Decoding the molecular grammar of protein condensates is crucial not only for expanding our understanding of cellular organization, but also for elucidating the mechanisms underlying widespread human pathologies like Alzheimer’s disease. Additionally, by deciphering this newly discovered layer of biological complexity, our research will open new avenues for developing innovative therapeutic strategies that address global health challenges, from aging-related neurodegenerative diseases to antibiotic resistance, ultimately shaping the next generation of biomedical breakthroughs.

Title of the talk:  Pathogenesis across genitourinary tissue barriers

Research plans: 

Background: Urinary tract infections (UTIs) are a global health concern, marked by high incidence, recurrence, morbidity and significant healthcare costs. They are also major drivers of the current antimicrobial resistance (AMR) crisis. The vast majority of UTI research has relied on animal or cancer cell models, using a limited number of uropathogenic strains, which often fail to mimic relevant aspects of human UTIs. I have contributed to bridge this gap through the development of human bladder tissue models for studying the interplay between host and uropathogen in patient-relevant scenarios.

Rationale: While both men and women can develop UTIs, women are disproportionately affected, with ~60% experiencing at least one episode in their lifetime. This has been largely attributed to the proximity of the female urethra to the anus, which fuelled extensive research into the gut-bladder axis. However, the role of the vagina, located between these two sites, has been significantly overlooked. Recent evidence suggests that the vagina may play a more important role during UTI, rather than just being a transition place for uropathogens.

Main objectives: As a future group leader, I aim at building a team to explore pathogenesis across the urinary tract-vagina axis in an innovative and comprehensive manner. To address key gaps in the UTI field and advance treatment strategies, my research program will focus on three main questions: 

1)     How do uropathogens establish a foothold on human genitourinary tissues?

2)     What defense mechanisms do these tissues deploy? and how do these responses influence infection recurrence versus clearence?

3)     How can we develop antibiotic-sparing strategies to improve UTI treatment?

These objectives will be pursued combining advanced human tissue modelling with cutting-edge microscopy and omics approaches.

Impact: Exploring pathogenesis across the urinary tract-vagina axis with human complex systems will drive a paradigm shift in the UTI field and beyond, bridging the gap between animal models and human studies. It will transform how we understand and treat UTI by uncovering fundamental aspects of the crosstalk between different tissue niches and uropathogen strategies, while inspiring the development of novel therapeutics to combat AMR.

We are very pleased to announce that the special session "PIs of Tomorrow - The Future of Swiss Research" will be held at the LS² Annual Meeting 2025.

This session offers an opportunity for postdocs and junior researchers interested in pursuing an academic career to present a talk similar in format to a professorship application interview. A jury panel of professors will evaluate the presentations and provide feedback in a one-on-one session afterward. Only applicants with ties to Switzerland will be considered. As in 2019 in 2020, in 2021, in 2022, in 2023, and in 2024 the PIOT session will be again a plenary session.

APPLY HERE.

The PIs of Tomorrow chairs: Dr. Timur Ashirov, Dr. Rubén D. Manzanedo, Dr. Leyla Loued-Khenissi, Dr. Milad Radiom

• • Lucia Prieto-Godino: 2017 Jury & Public Award Winner
    Awarded FENS EJN Young Investigator Prize, L’Oreal-UNESCO for women in science Fellowship
    Now Group Leader at the Francis Crick Institute (London, UK)
  • Alexander Harms: 2018 Jury Award Winner
    Awarded SNSF Ambizione
    Now Assistant Professor of Molecular Phage Biology at ETH Zurich (CH)
  • Andreas Moor: 2018 Public Award Winner
    Awarded SNSF Eccellenza, ERC Starting Grants
    Now Assistant Professor of Systems Physiology at ETH Zurich (CH)
  • Michael Zimmermann: 2019 Public Award Winner
    Awarded SNF Advanced Postdoc Mobility Fellowship, SwissTB Award, EMBO Long-Term Fellowship, SNF Early Postdoc.Mobility Fellowship Now Now Group Leader at EMBL (DE)
  • Francesca Ronchi: 2019 Jury Award co-Winner
    Awarded SNSF-MHV Postdoctoral fellowship, ECCO Grant
    Now Associate Professor at Charité – Universitätsmedizin Berlin (DE)
  • Jean-Philippe Krieger: 2019 Jury Award co-Winner
    Awarded an SNF postdoctoral fellowship
    Now PI at the VAGALAB and University of Gothenburg (Sweden) 
  • Thomas O. Auer: 2020 Jury Award Winner
    Awarded an Ambizione Fellowship, Now Assistant Professor at the University of Fribourg (CH) 
  • Joachim Moser von Filseck: 2020 Public Award Winner
    Now Research Group Leader at the Heidelberg University Biochemistry Center (DE) 
  • Elisa Araldi: 2021 Jury Award Winner
    Now Assistant ProfessorAssistant Professor at the Università degli Studi di Parma (IT) 
  • Karina Silina: 2021 Public Award Winner
    Now Senior Researcher at the Institute for Experimental Immunology, University of Zurich 
  • Alicia Michael:  2022 Jury Award Winner
    Now Postdoctoral Researcher at Friedrich Miescher Institute for Biomedical Research 
  • Adam Gosztolai: 2022 Public Award Winner
    Now a Human Frontiers Postdoctoral Fellow in the group of Pierre Vandergheynst at EPFL (CH) and Research Affiliate at Massachusetts Institute of Technology (US) 
  • Dr. Rubén Delgado Manzanedo: 2023 Jury Award Winner
    Now Lecturer at the Department of Environmental Systems Science, ETH Zurich (CH) 
  • Dr. Bernadette Jana Stolz-Pretzer: 2023 Public Award Winner
    Now Scientist at EPFL (CH)